摘要：The COVID-19 pandemic posed a challenge for clinical management of a new lung dis-ease that was characterized by inflammation,endothelial cell dysfunction,and throm-bosis,which occur after the replication phase of infection of severe acute respiratory syndrome coronavirus 2(SARS-CoV-2).There are many laboratory models of active SARS-CoV-2 infection in mice,reflecting an acute lung injury in an otherwise healthy animal,but there is a lack of accurate animal models of the postviral inflammatory phase of the COVID-19 lung reflecting severe disease.The monocrotaline(MCT)-treated rat is a widely used laboratory model of pulmonary hypertension(PH).Not often discussed,however,are the observed changes in inflammation,edema,fibrosis,and microthrom-bosis in the lung prior to PH.At the cellular level,there is loss of pneumocytes and endotheliopathy,and at the molecular level the MCT rat lung is characterized by a pro-inflammatory cytokine profile,namely elevated interleukin 6,transforming growth fac-tor β and tumor necrosis factor,M1 macrophage phenotype,and dysregulation of the angiotensin converting enzyme(ACE)/ACE2 balance.The systems-level pathophysiol-ogy of the MCT-treated rat includes progressive cardiopulmonary dysfunction.The MCT-treated rat clearly differs from the COVID-19 lung in terms of the triggers for pathology,but there are many parallels apparent in both the MCT-treated rat and the COVID-19 lung.The MCT-treated rat lung as a model of the COVID-19 lung may pro-vide an in-depth understanding of the factors that drive the lung to more severe pathol-ogy,treatments that benefit lung recovery,or the factors that prove a useful research platform for future emerging respiratory threats of similar pathology.

摘要：Background:Most mutations in the COL6A3 gene lead to collagen Ⅵ-related myopa-thies.This is due to a reduced expression or mislocalization of the COL6A3 protein.Therefore,studying the consequence of knocking out the Col6a3 gene in mouse mod-els is relevant,but the Col6a3 mouse models reported so far do not entirely abolish COL6A3 protein expression. Methods:Here,we present the development,validation and preliminary phenotypic characterization of a novel CRISPR-based knockout mouse model targeting Col6a3 exon 3(Col6a3d3/d3). Results:In this mouse model,Col6a3 mRNA is still expressed at a similar level to wild-type littermates,although the expected protein is undetectable by mass spec-trometry.Histological analysis of Col6a3d3/d3 quadriceps revealed an abnormally high frequency of muscle cells with internally nucleated muscle cells,consistent with a myopathy phenotype.Interestingly,Col6a3d3/d3 mice are smaller in size,with their fat,muscle,and bone kept proportional compared to wild-type littermates. Conclusions:In summary,we performed the validation and preliminary phenotypic characterization of a novel Col6a3 knockout mouse model that could be further charac-terized and used to study COL6A3 biology and model collagen Ⅵ-associated diseases.

摘要：Background:Pulmonary hypertension(PH)is a life-threatening condition that can be triggered by pulmonary thromboembolism(PTE),which causes abrupt increases in pulmonary artery pressure and resistance.Although Doppler echocardiography is a useful screening tool,its ability to accurately reflect rapid hemodynamic changes dur-ing acute PTE remains limited.The Flowire catheter allows for real-time assessment of intravascular flow and may offer better insight into these changes. Aims:The aims were to investigate changes in pulmonary artery hemodynamics meas-ured using a Flowire catheter and to validate the accuracy of Doppler echocardiogra-phy in assessing these changes in dogs with acute pulmonary thromboembolism(PTE). Methods:Hemodynamic and echocardiographic data were obtained from 10 an-esthetized female beagles using a Flowire catheter and echocardiography at three preload conditions:baseline,bolus loading,and an acute pulmonary hypertension state induced by a 300-pm dextran microsphere injection. Results:With increases in pulmonary artery pressure and pulmonary vascular resist-ance,the proximal and distal pulmonary artery flow peak measured using the Flowire catheter significantly decreased during the acute pulmonary hypertension period.Echocardiography did not accurately capture these hemodynamic changes and tended to overestimate pulmonary artery flow peak in the distal pulmonary artery. Conclusion:Doppler echocardiography has limitations in accurately reflecting com-plex hemodynamic changes during acute PTE.In contrast,Flowire catheterization provides additional and precise local hemodynamic information.

摘要：MicroRNAs(miRNAs)are crucial in diverse biological processes.In recent years,ex-tensive research has significantly advanced our understanding of miRNA biogenesis,function,and its implications in various biological processes and diseases.In devel-opment,miRNAs precisely regulate gene expression to ensure proper organismal growth.miRNAs serve as essential modulators of cell proliferation and differentia-tion,thereby determining cell fate.Regarding the regulation of apoptosis,miRNAs play a significant role in controlling programmed cell death.Moreover,in metabolism,miRNAs are involved in modulating various pathways.This review examines the latest advancements in miRNA research,encompassing their biogenesis,functional roles,and involvement in various biological processes and diseases.A specific emphasis is placed on the roles of miRNAs in development,cell proliferation,apoptosis,and metabolic regulation.Additionally,cutting-edge technologies were discussed for the potential therapeutic applications of miRNA-based strategies.

摘要：Background:Sudden sensorineural hearing loss(SSNHL),often associated with tin-nitus,significantly impacts individuals' quality of life.Current treatments,such as free drugs via intravenous or intratympanic(IT)administration of dexamethasone(DEX)and lidocaine,face limitations like low bioavailability and rapid drug clearance.To address these challenges,we developed a local co-delivery system combining DEX microcrystals(DEX MCs)and lidocaine-loaded poly(lactic-co-glycolic acid)(PLGA)non-spherical microparticles(LPNMs)for sustained drug release in the inner ear. Methods:DEX MCs and LPNMs were prepared using the traditional precipitation technique and double emulsion-solvent evaporation,respectively.After character-izing physicochemical properties and drug release kinetics,they were dispersed in sodium hyaluronate solution for IT injection,then in vivo pharmacokinetics and bio-compatibility in guinea pigs were studied. Results:DEX MCs exhibited stable dissolution,while LPNMs provided sustained li-docaine release,reducing potential side effects.In vivo studies in guinea pigs demon-strated prolonged drug retention in the perilymph and improved pharmacokinetics.Histological evaluation confirmed the good biocompatibility of this combined delivery system,with no significant inner ear damage observed. Conclusion:This co-delivery system can be used as a depot for delivering both DEX and lidocaine to the inner ear and offers a promising approach for the synergistic treatment of SSNHL associated with tinnitus.

摘要：Over 550000 people in the U.S.require hemodialysis for management of end stage renal disease(ESRD).When anatomy restricts fistula creation,arteriovenous grafts(AVG)are implanted.AVGs have poor primary patency and high risk of infection,highlighting a need for better alternatives.Previous AVG large animal models were limited by high complication rates and short-term follow-up.This study investigates the safety and durability of an ovine bilateral carotid-jugular AVG model.Eight fe-male sheep underwent bilateral carotid-jugular AVG implantation via a single lon-gitudinal incision overlying the trachea.Ringed PTFE grafts were anastomosed in a"lazy-S"configuration to provide the laxity needed to prevent avulsion and mini-mize kinking with neck movement.Post-operatively,sheep were evaluated daily to monitor for complications.Duplex ultrasonography of the grafts was performed at regular intervals out to 6 months to evaluate patency.At 6 months,angiography and duplex was performed followed by explant for gross and histologic analysis.Technical success was achieved in 16 of 16(100％)graft implants.No major com-plications,including stroke,anastomotic disruption,infection,wound breakdown,or death occurred.Primary patency of control PTFE grafts was 75％at 6 months,paralleling reported rates in humans.Bilateral carotid-jugular AVG implantation in sheep is a safe and durable model for self-controlled long-term evaluation of AVG conduit technology.

摘要：Background:Chaihu Guizhi Decoction(CGD)is a classical prescription in traditional Chinese medicine(TCM)that has been shown to be effective against infection and depression.However,the mechanisms of action of CGD in treating patients with de-pression who are also infected with a virus remain unknown.This study investigated the pharmacological mechanisms of CGD in treating depression-like mice infected with influenza A virus(IAV). Methods:The acute depression-like mouse model infected with IAV was established.The effects of CGD on alleviating depression-like symptoms were observed using the sucrose preference test and monoamine neurotransmitter expression.Additionally,the effectiveness of CGD against infection was assessed by examining the relative ex-pression of the M gene and pathological changes.To evaluate the anti-inflammatory effects of CGD,the levels of cytokines were measured,and the Th17/Treg ratio was analyzed to evaluate the immunomodulatory effects of CGD. Results:The study results show that CGD enhanced the rates of sucrose preference and raised the contents of neurotransmitters dopamine(DA)and norepinephrine(NE).CGD treatment led to a reduction in lung index and the relative expression of the M gene,along with improvements in pathological changes caused by IAV.Furthermore,the levels of cytokines were decreased after treatment with CGD,and the imbalance in the ratio of Th17/Treg was corrected via a reduction in the number of Th17 cells after treatment. Conclusions:CGD has a therapeutic effect in mice with depression-like symptoms infected with IAV,increasing the levels of DA and NE,downregulating M gene expres-sion,calming the cytokine storm,and preserving the homeostasis of Th17/Treg cells.

摘要：Background:Acute pancreatitis(AP)is a severe inflammation of the pancreas,marked by elevated enzyme levels,cellular inflammation,and necrosis.Recent studies emphasize the critical role of inflammation in AP progression.Tirzepatide,a multi-target agonist of glucagon-like peptide-1(GLP-1)and glucose-dependent insulinotropic polypeptide(GIP)receptors,has demonstrated notable anti-inflammatory and metabolic benefits. Methods:This study explores the therapeutic potential of Tirzepatide in pancreati-tis induced by L-arginine in rats,focusing on enzymatic markers,cytokine profiles,oxidative stress,and histological outcomes.Over 27days,rats were distributed into Control,Tirzepatide,L-Arginine,and L-Arginine+Tirzepatide groups,with the latter receiving L-Arginine to induce pancreatitis followed by Tirzepatide administration. Results:L-Arginine significantly elevated serum amylase,lipase,and inflammatory mediators(I L-6,IL-4,and IL-10),alongside oxidative stress markers and histopathological deterioration.Conversely,the L-Arginine+Tirzepatide group exhibited reduced lipase and IL-6 levels,suppressed reactive oxygen species(ROS)generation,and enhanced anti-inflammatory cytokines IL-4 and IL-10.Histopathological analysis revealed reduced necrosis and tissue damage in the L-Arginine+Tirzepatide group compared to the L-Arginine group,indicating Tirzepatide's possible protective effects.Immunofluorescence studies further demonstrated increased p-Akt expression,supporting the role of Tirzepatide in cellular repair and recovery. Conclusion:These findings highlight Tirzepatide's ability to mitigate pancreatic damage through antioxidant and anti-inflammatory mechanisms,underscoring its potential as a pharmacological agent for acute pancreatitis.

摘要：Background:Intracerebral hemorrhage(ICH)remains a devastating neurological disorder with limited therapeutic options.Neural stem cell(NSC)-based therapies have emerged as a potential regenerative approach,yet the molecular mechanisms regulating NSC behavior require further elucidation.The role of miR-21 in NSC differentiation and proliferation during ICH recovery remains unexplored. Methods:In vitro NSC cultures were analyzed for miR-21 expression dynamics dur-ing differentiation via qPCR.Lentiviral overexpression and knockdown of miR-21 were employed to assess its functional impact.The SOX2/LIN28-let-7 pathway was investigated using Western blot,luciferase reporter assays,and immunofluorescence.In vivo,miR-21-overexpressing NSCs were transplanted into a murine ICH model,with neurogenesis evaluated by immunostaining and neurological recovery assessed through behavioral tests(mNSS,rotarod). Results:miR-21 expression significantly increased during NSC differentiation,correlating with reduced SOX2 levels.Mechanistically,miR-21 directly targeted SOX2,disrupting the SOX2/LIN28-let-7 axis to promote NSC proliferation and lineage commitment.In ICH mice,transplantation of miR-21-overexpressing NSCs enhanced neurogenesis and improved motor coordination and neurological deficits at 28days post-transplantation. Conclusions:Our findings identify miR-21 as a critical regulator of NSC plasticity through SOX2/LIN28-let-7 signaling,highlighting its therapeutic potential for enhancing neuroregeneration and functional recovery in ICH.Targeting miR-21 may represent a novel strategy to optimize NSC-based therapies for hemorrhagic stroke.

摘要：Background:The traditional Sox10Dom/+mouse breeding strategy is costly and time-consuming,so this study aims to optimize the breeding method and improve the sci-entific research efficiency. Methods:We select the offspring from mating B6C3Fe Sox10Dom/+male mice with C57BL/6J female mice,and name the progeny B6C3Fe-g.Further,conduct separate self-breeding for both the B6C3Fe and B6C3Fe-g strains,adhering to the principle of pairing mutants with non-mutants.By comparing the number of offspring,survival rates,and the phenotype of aganglionosis in the colon,a comprehensive evaluation of their breeding capacity and phenotypic stability is conducted. Results:Sanger sequencing results show that the mutation sites of B6C3Fe and B6C3Fe-g mice are consistent.After fluorescent staining of intestinal nerves,it was found that the heterozygous mice of the two strains had neuronal deletion in the distal colon,and this pathological phenotype was consistent with the pathological features of the diseased colon of Hirschsprung disease(HSCR).However,compared with the B6C3Fe strain,the B6C3Fe-g strain has a higher number of offspring and greater survival rates. Conclusions:The breeding strategy of the B6C3Fe-g strain ensures genetic and phe-notypic stability,while improving reproductive efficiency,and is an ideal scheme for breeding Sox10Dom/+mice.

摘要：Oral squamous cell carcinoma(OSCC)constitutes 90％of oral tumors.Advanced cases severely impair patients' life quality of life due to anatomical location and limited ther-apies.Conventional treatments often induce drug resistance or recurrence.Patient-derived xenograft(PDX)models are widely used to simulate tumor progression and drug responses,serving as translational tools for precision medicine.This study aimed to establish drug-resistant OSCC PDX models.Human OSCC tissues were transplanted into immunodeficient mice and passaged(P1-P2).At P2(tumor volume:40-80mm3),mice received cisplatin(1 mg/kg,three times/week)with cetuximab(1 mg/kg,weekly),GSK690693(10mg/kg,five times/week),or rapamycin(4mg/kg,five times/week).PDX tissues from groups with less-therapeutic response(manifested as larger tumor volumes)were serially passaged to assess treatment efficacy.Tumor tissues with di-minished drug sensitivity underwent histopathological analysis and identified stability of their tumor characteristics using hematoxylin-eosin(HE)and immunohistochemi-cal staining after one additional passage and retreatment.Results demonstrated that successive passaging accelerates tumor growth.First-generation treatments showed universal sensitivity.At P2,cisplatin-cetuximab and rapamycin groups remained sen-sitive,whereas GSK690693 efficacy declined.Continued passaging of GSK690693-treated tumors confirmed resistance,as evidenced by exhibiting enhanced malignant characteristics at histological level.The GSK690693-resistant model was established first,whereas resistant models of other treatment groups were established according to similar protocols.These findings suggest that sequential passaging and drug expo-sure in PDX models recapitulated clinical tumor evolution,enabling the development of drug-resistant OSCC models.This study can offer methodological insights for pre-cision therapy of OSCC.

摘要：This study aims to conduct a comparative study of two strains of laboratory rats,hooded and Wistar,to select a suitable alternative to nude rats for ovarian tissue xenotransplantation.The study investigated the effects of ovarian tissue transplantation using three experimental groups:(1)the control group receiving vitrified-warmed human ovarian tissue,(2)the OTW(ovarian tissue transplantation in Wistar)group with human ovarian tissues in Wistar rats,and(3)the OTH(ovarian tissue transplantation in hooded)group with ovarian tissues transplanted into hooded rats.A total of 12 rats(6 each from the two transplantation groups)were used,with tissue samples implanted in the dorsal neck muscles.Outcomes were evaluated using histological analyses,including hematoxylin and eosin and Masson's trichrome staining,as well as immunohistochemical assessments of CD31 for angiogenesis,fibrosis,and necrosis.The OTH group exhibited more blood vessel numbers and the Vegf gene expression than both the OTW and control groups,with significantly lower levels of fibrosis and necrosis compared to the OTW and control groups.The study indicates that hooded rats could serve as a valuable alternative for specific research when nude mice are not available.Their immune systems are more compatible with human ovarian tissue transplants than Wistar rats,and they exhibit calmer behaviors,making them better suited for laboratory work.

摘要：Background:Multiple sclerosis(MS)is a chronic disease of the central nervous system(CNS),exhibiting hallmarks of both inflammation and neurodegeneration and with lim-ited treatment options.The intricate nature of MS pathophysiology and its variable progression pose severe challenges for the development of effective therapies.The experimental autoimmune encephalomyelitis(EAE)MS model,in its most common form,is an aggressive disease,which is not representative of the MS course and offers a limited time window for drug evaluation.This study aimed to generate an attenu-ated EAE variant,which extends the clinical testing window while preserving the high incidence of the standard EAE model. Methods:Components of the EAE induction protocol were titrated to develop a milder disease profile.In a subsequent drug trial using the MS medication fingolimod hydrochloride(FTY,Gilenya),the new variant was validated under prophylactic and therapeutic treatment regimens. Results:The attenuated EAE variant retains the standard hallmarks of neuroinflam-mation and,crucially,significantly extends the time frame for clinical drug testing.Unlike the standard variant,where FTY efficacy could only be demonstrated by pro-phylactic treatment,the attenuated variant facilitated differentiation of drug effects by therapeutic treatment initiated early in the acute phase of disease. Conclusion:The new EAE variant is suitable for use in preclinical assessment of can-didate therapeutics and the identification of targetable molecular mechanisms under-pinning disease development and progression.This study illustrates the importance of optimizing and refining the experimental tool to enhance the translational success of the candidate therapeutics for MS.

摘要：Background:Hemorrhagic expansion into the fourth ventricle is an independent risk factor for poor outcomes in intraventricular hemorrhage(IVH)patients.However,to date,available animal models of IVH are limited to models of supratentorial ven-tricular hemorrhage,and there are no specific models of fourth ventricle hemor-rhage.This limitation hinders comprehensive basic research and the understanding of the pathophysiological changes that occur following fourth ventricle hemorrhage.Therefore,the development of an animal model of fourth ventricle hemorrhage is highly important. Methods:In this study,a novel rat model of fourth ventricle hemorrhage was estab-lished via autologous blood injection through the foramen of Magendie.Anesthetized rats were positioned in a stereotaxic apparatus with their heads tilted downward at an angle of approximately 20° relative to the vertical axis.A needle was inserted through the foramen,and autologous blood obtained from the rat's heart was injected into the fourth ventricle via a microinfusion pump.Systematic evaluations of the model were conducted using small-animal magnetic resonance imaging,histopathological analysis,and neurological function assessment. Results:The rats developed stable and reproducible fourth ventricle hematomas and ventricular dilation.They also exhibited acute-phase hydrocephalus and pathological features of perilesional brain tissue injury,with observed neurological deficits compa-rable to patients with fourth ventricle hemorrhage. Conclusion:This model successfully recapitulates the clinicopathological and patho-physiological characteristics of patients with fourth ventricle hemorrhage and can be utilized for further investigation into the pathophysiological mechanisms underlying posthemorrhagic hydrocephalus and perilesional brainstem tissue injury.

摘要：Background:Vaccinia virus(VACV)and mpox virus(MPXV)belong to the ortho-poxvirus genus and share high genetic similarity,making VACV widely used in the mpox pandemic.CAST/EiJ mice have been widely used for studying orthopoxvirus infection.However,the histopathological features of CAST/EiJ mice with mpox virus(MPXV)and vaccinia virus(VACV)infections have not been fully elucidated. Methods:Four group of CAST/EiJ mice were challenged with low-dose VACV(103 PFU,VACV-L),high-dose VACV(106 PFU,VACV-H),MPXV(106 PFU)or PBS via in-traperitoneal route,and the disease signs and body weight were monitored daily.Subsequently,viral loads and titers in the blood and spleen of CAST/EiJ mice were analyzed via qPCR and TCID50 assay.Finally,the spleen samples were analyzed for histopathological,immunohistochemical and RNA-seq. Results:Herein,we found that VACV-L and MPXV caused splenomegaly via the intra-peritoneal route,whereas VACV-H caused rapid lethality with limited splenomegaly.Transcriptome analysis from spleen revealed significant differences in gene expres-sion between VACV-L and VACV-H groups,but the differentially expressed genes induced by splenomegaly between VACV-L and MPXV groups were highly similar.Furthermore,pathway enrichment analysis demonstrated that the VACV-L,VACV-H,and MPXV groups were all associated with the calcium,MAPK,and PI3K-Akt signal-ing pathway.Compared to the lethal infection observed in VACV-H group,the sple-nomegaly in the VACV-L and MPXV groups was characterized by extramedullary hematopoiesis and increased macrophages infiltration in the red pulp.Transcriptome analysis of the spleen demonstrated that the Wnt,tumor necrosis factor(TNF),and transforming growth factor β(TGF-β)signaling pathways may promote splenomegaly by modulating granulocyte infiltration and inflammatory responses.Compared to VACV-L group,the limited splenomegaly but lethality in VACV-H-infected mice might be associated with extensive splenic necrosis,diffuse congestion,and hemorrhage in the red pulp,as well as changes in the cGMP-PKG,Ras signaling,and Fc gamma R-mediated phagocytosis pathways. Conclusions:Our findings systematically compared the pathogenicity of VACV and MPXV in CAST/EiJ mice,incorporating splenic transcriptome analysis to provide in-sights into the potential molecular mechanism behind orthopoxvirus-induced spleno-megaly in CAST/EiJ mice.

摘要：Background:Chaetomorpha aerea,a marine green alga,has drawn attention because of its rich phytochemical constituents and therapeutic benefits.Using an integrated approach that combined in vitro,in vivo,and in silico approaches,this work examined the antioxidant,anti-inflammatory,and antidiabetic qualities of acetone extract of C.aerea(AECA). Methods:Total phenolic and flavonoid concentrations of AECA were measured.Antioxidant activity was assessed using the DPPH and ABTS free radical scaveng-ing assays.In vitro protein denaturation and in vivo carrageenan-induced paw edema models were employed to evaluate the anti-inflammatory potential,whereas antidia-betic activity was assessed using in vitro α-amylase inhibition and in vivo oral glu-cose tolerance test(OGTT).Molecular docking and ADME/T analysis were employed to further analyze bioactive compounds identified using gas chromatography-mass spectrometry(GC-MS). Result:Antioxidant activity demonstrated a minimum inhibitory concentration(IC50)of 107.44 μg/mL for DPPH and 118.23 μg/mL for ABTS.In vitro anti-inflammatory assays indicated a suppression of protein denaturation at a concentration of 102 μg/mL(IC50),where AECA(400 mg/kg)resulted in a 27％reduction in paw edema at 6 h in the mouse model.In vitro antidiabetic test indicated α-amylase inhibition with an IC50 value of 70.72 μg/mL,and in the OGTT,a significant lowering of blood glu-cose was recorded at 120 min in mice.Strong binding affinities were observed for stigmasta-5,24(28)-dien-3-ol,identified using GC-MS,with values of-9.9 kcal/mol for α-amylase and-8.0 kcal/mol for cyclooxygenase-2. Conclusion:C.aerea serves as an effective natural remedy for oxidative stress,inflam-mation,and hyperglycemia.These findings advocate for further clinical and mecha-nistic investigations to optimize therapeutic efficacy.

摘要：Background:The Cre/loxP system is most popular in mice,but its application in rats has largely lagged far behind.The rat is vital laboratory animal,especially in toxico-logical and neurological studies.Generating genetic tools to manipulate neurons in rats could benefit neurological research. Methods:Using the CRISPR/Cas9 system,we inserted a Cre cassette into endog-enous Thy1 and NeuN loci.Thy1-Cre rats featured a downstream P2A-linked insertion,while NeuN-Cre was inserted at the transcriptional start site.The Cre activity was assessed by crossing with a Cre reporter(Rosa26'mCherry)rat and through analyzing mCherry expression patterns.The specificity of cell type was further confirmed by immunofluorescence with NeuN antibody.Phenotypic consequences were assessed by crossing with ND1LSL rats to deplete ND1,followed by monitoring weight/survival and conducting motor function tests. Results:We generated two neuron-specific rats(Thy1-Cre and NeuN-Cre),which ex-hibited high neuron-specific Cre expression in brain and spinal cord with minor leak-age in other tissues.Thy1-Cre showed minor leakage in spleen,lung and kidney while NeuN-Cre showed minor leakage in spleen and kidney.ND1Thy1-Cre and ND1NeuNCre rats both showed decreased body weights and survival times.The ND1NeuN-Cre rats died within two weeks,while ND1Thy1-Cre rats lived longer with impaired motor function. Conclusions:We successfully generated two neuron-specific NeuN-Cre and Thy1-Cre rats,and systemically analyzed their expression pattern.

摘要：Background:The two-kidney two-clip(2K2C)rat model is widely used in hyperten-sion,stroke,and drug studies.However,knowledge of this model is quite limited. Methods:In this study,U-shaped silver clips with inner diameters of 0.3,0.25,and 0.2 mm were used to narrow bilateral renal arteries,inducing different extents of blood flow reduction for preparing 2K2C rats.Blood pressure(BP)was continuously measured during 2K2C procedures until 10h after 2K2C,and long-term assessments of BP,organ damage,and serum biochemistry were performed at 1,2,4,and 6 weeks. Results:BP increased immediately when the 2K2C rats regained consciousness from anesthesia,with a 100％incidence of hypertension on the day of operation,and in-creased to a plateau at 2 weeks for 0.2 mm clips(248 mmHg),4 weeks for 0.25 mm clips(219 mmHg),and perhaps 6 weeks for 0.3 mm clips(206 mmHg).BP levels displayed a negative correlation with clip sizes.Organ damage,including aortic and cardiac hyper-trophy,cerebrovascular and cardiovascular injury,and renal atrophy or compensatory enlargement,occurred as early as 1 or 2 weeks after 2K2C.Routine serum biochemistry indicated organ dysfunction primarily at 4-6 weeks in 0.2 mm clips,whereas aspartate aminotransferase appeared a sensitive biomarker for early organ damage. Conclusion:2K2C can produce severe hypertension and multi-organ damage in a short time.2K2C rats in 0.2 mm clips can be used as a hypertensive emergency model.This study provides crucial insights for guiding the development of targeted interventions.