摘要
目的探讨磷脂酰肌醇3．激酶（P13K）／丝氨酸-苏氨酸蛋白激酶（Akt）信号转导通路在人参皂甙Rb1预先给药减轻糖尿病大鼠心肌缺血再灌注损伤中的作用。方法雄性SD大鼠，体重250～300g，采用腹腔注射链脲佐菌素的方法制备糖尿病模型，造模成功的糖尿病大鼠48只，饲养8周后，采用随机数字表法，将其随机分为4组（n=12）：心肌缺血再灌注组（I／R组）、人参皂甙Rb1预先给药组（R组）、人参皂甙Rbl预先给药＋P13K抑制剂渥曼青霉素组（RW组）和渥曼青霉素组（W组）。采用结扎左冠状动脉前降支30min再灌注的方法建立心肌缺血再灌注损伤模型。RW组和W组于缺血前20min静脉注射渥曼青霉素15ug／kg，R组和RW组于缺血前10min静脉注射人参皂甙Rb140mg／kg。再灌注120min时采集动脉血样，测定血清肌酸激酶（CK）和乳酸脱氢酶（LDH）的活性；然后处死大鼠，取心肌组织，采用四氮唑法测定心肌梗死面积；采用TUNEL染色法检测心肌细胞凋亡，计算心肌细胞凋亡指数（AI）；采用Westernblot法测定心肌组织Akt和磷酸化Akt（p-Akt）表达。结果与I／R组比较，R组血清CK和LDH活性、心肌梗死面积和心肌细胞AI降低，心肌组织P—Akt表达上调（P〈0．05）；与R组比较，RW组血清CK和LDH活性、心肌梗死面积和心肌细胞AI升高，心肌组织p-Akt表达下调（P〈0．05）。结论人参皂甙Rb1预先给药通过PI3K／Akt信号转导通路减轻糖尿病大鼠心肌缺血再灌注损伤。
Objective To investigate the role of phosphatidylinositol 3-kinase （PI3K）/protein-serine-threonine kinases （Akt） signal pathway in ginsenoside Rbl pretreatment-induced attenuation of myocardial ischemiareperfusion （I/R） injury in diabetic rats.Methods Male SD rats weighing 250-300 g were used in this study. Diabetes mellitus was induced by intraperitoneal streptozotocin and confirmed by fasting blood glucose ≥ 16.7 mmol/L. Eight weeks after diabetes mellitus was induced, 48 rats were randomly divided into 4 groups （n = 12 each）： group myocardial I/R （group I/R）; group ginsenoside Rbl （group R）; group ginsenoside Rbl ＋ wort- mannin （PI3K inhibitor） （group RW） and group wortmannin （group W）. Myocardial I/R was induced by occlusion of anterior descending branch of left coronary artery for 30 min followed by 120 min reperfusion. Ginsenoside Rb1 40 mg/kg was injected iv at 10 min before ischemia in groups R and RW, while in groups RW and W wortmannin 15 ug/kg was injected iv at 20 min before ischemia. Arterial blood samples were collected at the end of 120 min reperfusion for determination of creatine kinase （CK） and lactate dehydrogenase （LDH） activities. The rats were then sacrificed. The infarct size was measured by tetrazolium method. Myocardial apoptosis was detected by TUNEL and apoptotic index （the number of apoptotic myocardial cells/the total number of myocardial cells） was calculated. The expression of Akt and phosphorylated Akt （p-Akt） was determined by Western blotting. Results Ginsenoside Rbl pretreatment significantly reduced the infarct size, myocardial cell apoptotic index and serum CK and LDH activities and up-regulated p-Akt expression in group R as compared with group I/R. The protective effects of ginsenoside Rbl against myocardial I/R injury were significantly attenuated by wortmannin pretreatment in group RW compared with group R. Conclusion PI3K/Akt signal pathway is involved in the protective effects of ginsenoside Rb1 against myocardial
出处
《中华麻醉学杂志》
CAS
CSCD
北大核心
2012年第3期358-360,共3页
Chinese Journal of Anesthesiology
基金
基金项目：国家自然科学基金（30672033）
