摘要
目的评价Janus激酶2／信号转导与转录激活子3（JAK2／STAT3）信号通路在川芎嗪减轻大鼠心肌缺血再灌注损伤中的作用。方法健康成年雄性Wistar大鼠64只，体重250-300g，采用随机数字表法，将大鼠随机分为4组（n=16）：假手术组（S组）、缺血再灌注组（工／R组）、川芎嗪组（T组）和JAK2特异性抑制剂AG490组（AG组）。采用结扎左冠状动脉前降支30min，再灌注120min的方法制备心肌缺血再灌注损伤模型。S组开胸暴露心脏，左冠状动脉前降支仅穿线；T组于阻断左冠状动脉前降支前20min静脉注射川芎嗪20mg／kg；AG组于阻断左冠状动脉前降支前20min静脉注射川芎嗪20mg／kg，再灌注前5min静脉注射AG4903μg／g。再灌注120min时，取下腔静脉血样，测定血清肌酸激酶（CK）及乳酸脱氢酶（LDH）的活性；观察心肌超微结构，计算心肌梗死体积百分比。结果与S组比较，I／R组、T组和AG组血清CK和LDH的活性升高（P〈0．01）；与UR组比较，T组血清CK、LDH活性和心肌梗死体积百分比降低，AG组血清CK、LDH活性降低（P〈0．01）；与T组比较，AG组血清CK、LDH活性和心肌梗死体积百分比升高（P〈0．05）。T组心肌病理学损伤较I／R组和AG组减轻。结论JAK2／STAT3信号通路参与了川芎嗪减轻大鼠心肌缺血再灌注损伤的作用。
Objective To evaluate the role of Janus kinase 2/signal transducer and activator of transcription 3 （JAK2/STAT3） signaling pathway in attenuation of myocardial ischemia-reperfusion （I/R） injury by tetramethylpyrazine in rats. Methods Sixty-four healthy male Wistar rats weighing 250-300 g were randomly divided into 4 groups（ n = 16 each） ： sham operation group （group S）, myocardial I/R group （group I/R）, teramethylpyrazine group （group T） and AG490（a JAK2 inhibitor） group （group AG）. Myocardial I/R was induced by 30 min occlu- sion of left anterior desecending coronary artery （LAD） followed by 120 min reperfusion in groups I/R, T and A. In groups T and A teramethylpyrazine 20 mg/kg was injected iv 20 min before LAD occlusion. In group A AG490 3 μg/g was injected iv at 5 min before reperfusion. Blood samples were then taken from inferior vena cava at 120 min of reperfusion for measurement of serum creatine phosphokinase （CK） and lactose dehydrogenase （LDH） activities. Myocardial infarct size was then measured and myocardial tissue was obtained for microscopic examination. Results Serum CK and LDH activities were significantly higher in group I/R than in group S. Pretreatment with tetramethylpyrazine significantly decreased myocardial infarct size and I/R-induced increase in serum CK and LDH activities and histologic damage. The protective effect of tetramethylpyrazine against myocardial I/R injury was attenuated by postconditioning with AG490. Conclusion JAK2/STAT3 signaling pathway is involved in attenuation of myocardial I/R injury by tetramethyl pyrazine in rats.
出处
《中华麻醉学杂志》
CAS
CSCD
北大核心
2011年第8期1005-1008,共4页
Chinese Journal of Anesthesiology
