Electro-acupuncture for STAT3 expression and nuclear translocation in hippocampal tissues of rats following cerebral ischemia/reperfusion

Lihong Kong; Xiaoling Zeng; Guojie Sun; Shenghong Liu

摘要：BACKGROUND: It has been found in recent years that STATS widely distributes in nervous system, including hippocampal CA1-3 region, dentate gyrus and cerebral neocortex, etc. Ischemic brain injury can cause the release of some cytokines and growth factors, while electro-acupuncture may have multi-level, multi-channel and multi-target protective and interventional effects on ischemic brain injury.OBJ ECTIVE: To observe the effects of electro-acupuncture on STAT3 expression and nuclear translocation in hippocampal CA1 region of rat models of brain ischemia/reperfusion.DESIGN: Randomized and controlled observation.SETTING: Staff Room of Acupuncture and Moxibustion, Department of Acupuncture and Bone Injury,Hubei College of Traditional Chinese Medicine; Tongji Medical College, Huazhong University of Science and Technology.MATERTALS: Seventy-two healthy SD rats, of clean degree and either gender, weighing (200±20) g, were provided by the Experimental Animal Center of Hubei College of Traditional Chinese Medicine. STAT3monoclonal antibody was purchased from Santa Cruz Company, USA, and G-6805 electro-acupuncture instrument was purchased from Shanghai Medical Electronic Instruments Factory.METHODS: This experiment was carried out in the comprehensive laboratory of Department of Acupuncture and Bone Injury, Hubei College of Traditional Chinese Medicine between September 2005 and February 2006.Seventy-two rats were randomly divided into 4 groups: ① control group(n =6): Untouched. ② Sham-operation group (n =18): Artery was isolated, but without inserting thread bolt.③ Model group (n =24): Rat models of local brain ischemia/reperfusion were established with modified suture occlusion. ④Electro-acupuncture group (n =24): Dazhui and bilateral Neiguan points were selected for electro-acupuncture treatment. No. 28acupuncture needle of 3.33 cm was used in the treatment A G-6085 electro-acupuncture instrument with continuous wave, frequency of 120 times/min, intensity of 1 mA, 30 min/time, was used. Acupuncture was conducted firstly at ischemia/reperfusion 3 hours, then once every 12 hours. STATS positive nuclear translocation in hippocampal CA1 region of rats was observed with immunohistochemical method at 24, 48 and 72 hours after brain ishcemia/reperfusion, and then STAT3 positive cells were counted.MAIN OUTCOME MEASURES: STATS positive cells and nuclear translocation in hippocampal CA1 region of rats in each group.RESULTS: All the 72 rats were involved in the result analysis. ①In the control group and sham-operation group, STAT3 positive cells with light cytoplasm and nucleus were decreased, and nuclear translocation was not found. ② In the model group, STATS positive cells were mostly found in the cytoplasm of the hippocampal CA1 region at the ischemic side of rats after ischemia/reperfusion 24 hours. They were significantly more than those in the sham-operation group and control group [(18.00±2.68), (g.00±1.35), (8.00±1.22) cells/ mm2, P ＜0.01], but cells with nuclear reaction were fewer; At ischemia/reperfusion 48 and 72 hours, STAT3 positive cells were increased, and they were significantly more than those of sham-operation group [(25.00±3.25), (35.00±3.52) cells/mm2, (15.00±1 .g3), (12.00±1.24) cells/mm2, P＜ 0.01＝. Positive cells with nuclear reaction were found dark-stained. ③At ischemia/reperfusion 24, 48 and 72 hours, STATS positive cells were strongly expressed in hippocampal CA1 region at ischemic side of rats of electro-acupuncture group, and they were significantly more than those of model group [(25±3.52), (50±6.31), (75±8.09) cells/mm2, P ＜ 0.01＝. STATS positive cells were gradually enhanced with time, and considerable STATS nuclear positive reaction cells were found.CONCLUSION: Electro-acupuncture can activate STAT3 protein expression in hippocampal tissue of rats with local brain ischemia/reperfusion, promote STATS nuclear translocation and function its neuroprotective effect.