DOI: 10.1002/ame2.70093
Pimobendan alleviates myocyte apoptosis and fibrosis associated with mitral regurgitation by targeting endoplasmic reticulum stress
Pakit Boonpala1
Sushawadee Tongta2
Nakkawee Saengklub3
Vudhiporn Limprasutr4
Sirinapa Srikam5
Wilawan Ji-au6
Tussapon Boonyarattanasoonthorn2
Yaowalak Panyasing7
Sarawut Kumphune8
Sarinee Kalandakanond-Thongsong9
Anusak Kijtawornrat1
1.Department of Physiology,Faculty of Veterinary Sci2.Chulalongkorn University Laboratory Animal Center(3.Department of Physiology,Faculty of Pharmacy,Mahid4.Chulalongkorn University Laboratory Animal Center(5.Department of Pathology,Faculty of Medicine,Chulal6.Department of Pathology,King Chulalongkorn Memoria7.Department of Pathology,Faculty of Veterinary Scie8.Biomedical Engineering Institute(BMEI),Chiang Mai 9.Department of Physiology,Faculty of Veterinary Sci
摘要：Background:Endoplasmic reticulum(ER)stress is an important factor in the develop-ment of numerous cardiovascular disorders;nevertheless,the association between ER stress and mitral regurgitation(MR)remains inadequately characterized.The mo-lecular mechanism of pimobendan(PIMO)that contributes to the delay in congestive heart failure(CHF)in MR associated with apoptosis and fibrosis is still unclear.Our aim was to examine the impact of PIMO on ER stress,apoptosis,and fibrosis in a chronic MR rat model.
Methods:MR was surgically induced in 10 Sprague-Dawley rats,with 5 serving as sham operation controls.At 8weeks postsurgery,the MR animals were randomly al-located into two groups:MR and MR+PIMO groups.PIMO was administered twice daily through oral gavage for 4weeks,whereas the sham and MR groups were ad-ministered similar quantities of drinking water.Echocardiography was conducted be-fore the delivery of PIMO as a baseline measure and at the end of the study.At the end of the investigation,hearts were procured for histopathological and ER stress evaluations.
Results:PI MO significantly maintained heart function and structural remodeling in the MR animals.PIMO significantly reduced MR-induced myocyte apoptosis(p=0.044)and fibrosis(p=0.002)by reducing the messenger RNA expression of genes associ-ated with ER stress(GRP78[glucose-regulated protein 78],ATF4[activating transcrip-tion factor 4],and CHOP[C/ERP homologous protein])compared to the MR group(p＜0.05,p＜0.01,and p＜0.001,respectively).
Conclusion:PIMO demonstrated cardioprotective benefits on heart function,myo-cyte apoptosis,and fibrosis by regulating ER stress in an MR-induced CHF rat model.
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论文发表日期：2025-11-30
在线出版日期：2026-01-09（本平台首次上网日期，不代表文献的发表时间）
页数：11( 2069-2079 )
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