熊果酸减轻糖尿病大鼠心脏缺血再灌注损伤  

Ursolic Acid Attenuate Myocardial Ischemia Reperfusion Injury in Diabetic Rats

作　　者：简磊[1] 高明杰[1] 夏旋[1] 

机构地区：[1]三峡大学仁和医院内分泌科,宜昌443000

出　　处：《天然产物研究与开发》2017年第5期843-848,共6页Natural Product Research and Development

摘　　要：探讨熊果酸(ursolic acid,UA)对糖尿病大鼠心脏缺血再灌注损伤的作用及潜在机制。通过腹腔注射链脲佐菌素诱导糖尿病大鼠模型。2周后糖尿病大鼠随机均分为假手术组(Sham)、心脏缺血/再灌注损伤组(MI/R)和熊果酸低、中、高剂量组(UA)。通过结扎冠状动脉左前降支构建心脏缺血再灌注损伤模型。测定各组大鼠乳酸脱氢酶(LDH),肌酸激酶(CK)、天门冬氨酸氨基转移酶(AST),心肌梗死面积、心脏收缩和舒张功能、磷脂酰肌醇(-3)激酶(PI3K)、蛋白激酶B(AKT)、磷酸化蛋白激酶B(p-AKT)、肿瘤坏死因子-α(TNF-α)、白介素-6(IL-6)、白介素1β(IL-1β)和B细胞淋巴因子2(BCL-2)、Bcl-2相关X蛋白(Bax)和TUNEL的表达。与Sham组相比,MI/R组心肌梗死面积明显增加,CK、AST、LDH、p-AKT、PI3K、IL-6、IL-1β、TNF-α、Bax和TUNEL的表达明显上调,而心脏收缩和舒张功能明显降低,BCL-2表达明显减少。与MI/R组相比,心肌梗死面积明减少,CK、AST、LDH、p-AKT、PI3K、IL-6、IL-1β、TNF-α、Bax和TUNEL的表达明显下调,而心脏收缩和舒张功能明显增强,BCL-2表达明显增加。三组之间AKT表达无差异。实验结果显示熊果酸预处理可通过减轻炎症和下调凋亡减轻糖尿病大鼠心脏缺血再灌注损伤,其作用机制与抑制AKT/PI3K信号通路激活相关。To explore the effect and potential mechanism of ursolic acid（UA） in myocardial ischemia reperfusion injury（MI/R） of diabetic rats. The model of diabetic rats were induced by injecting Streptozotocin and observed for 2 weeks. Diabetic rats were randomly divided into Sham group（Sham）,myocardial ischemia reperfusion injury group（MI/R）,and ursolic acid（low,middle,high） pretreatment group（UA）. The MI/R model was induced by ligating left anterior descending coronary artery of diabetic rats. The cardial Systolic and diastolic function,the cardial infarct size and the expression of acute cardiac injury biomarkers（CKMB,AST and LDH）,AKT,p-AKT,PI3K,IL-6,IL-1β,TNF-α,BCL-2 and TUNEL were examined in the rats of all groups. Compared with the Sham group,MI/R group had higher infarct size and the expression of CK,AST,LDH,p-AKT,PI3K,IL-6,IL-1β,TNF-α,Bax and TUNEL and with lower expression of BCL-2 and the cardial Systolic and diastolic function. Compared with the MI/R group,the UA group had lower expression of infarct size and the expression of CK,AST,LDH,pAKT,PI3K,IL-6,IL-1β,TNF-α,Bax and TUNEL with higher cardial Systolic and diastolic function and BCL-2 expression. There was no difference on the expression of AKT among three groups. UA pretreatment can protect diabetic rats against myocardial ischemia reperfusion injury by attenuating inflammation and apoptosis. The mechanism of which was associaing with suppressing the activation of AKT/PI3K signal pathway.

关 键 词：熊果酸 心脏缺血再灌注损伤 炎症 凋亡 

分 类 号：R542.2[医药卫生—心血管疾病]