灵仙新苷对大鼠心肌缺血再灌注损伤的保护作用及机制研究  

Protection effects and mechanism of clematichinenoside on myocardial ischemia-reperfusion injury in rats

作　　者：丁海燕[1] 李运曼[2] 方伟蓉[2] DING Haiyan;LI Yunman;FANG Weirong(School of Pharmacy, Xinjiang Medical University, Urumqi 830011, China;Key Laboratory of Natural Medicines, Department of Physiology, China Pharmaceutical University, Nanjing 210009, China)

机构地区：[1]新疆医科大学药学院,新疆乌鲁木齐830011 [2]中国药科大学药理学教研室天然药物重点实验室,江苏南京210009

出　　处：《药物评价研究》2018年第4期547-551,共5页Drug Evaluation Research

基　　金：新疆维吾尔自治区自然科学基金资助项目(2015211C001)

摘　　要：目的考察灵仙新苷对大鼠心肌缺血再灌注损伤(MIRI)的保护作用,并阐述可能的作用机制。方法 SD大鼠随机分为6组:假手术组、模型组、丹参酮IIA(阳性药,16 mg/kg)组和灵仙新苷低、中、高(8、16、32 mg/kg)组,连续ig给药7 d;采用结扎冠状动脉左前降支法制备大鼠MIRI模型,缺血40 min再灌120 min;试剂盒法检测MIRI大鼠血清肿瘤坏死因子-α(TNF-α)、白介素-1β(IL-1β)、白介素-6(IL-6)水平;TTC染色法检测心肌梗死率,流式细胞术检测心肌细胞凋亡率;Western blotting法检测心肌组织中Bcl-2、Bax、TNF-α及Caspase-3的蛋白表达水平。结果与模型组比较,灵仙新苷(8、16、32 mg/kg)显著降低MIRI模型大鼠血清中TNF-α、IL-1β、IL-6水平,心肌梗死率和心肌细胞凋亡率;明显上调Bcl-2蛋白表达水平,下调Bax、TNF-α、Caspase-3蛋白表达水平,且均具有显著性差异(P<0.05、0.01)。结论灵仙新苷对MIRI大鼠心肌具有保护作用,其机制可能与抑制TNF-α,调节Bcl-2/Bax蛋白平衡,减少MIRI诱导的心肌细胞凋亡有关。Objective To investigate the protective effects of clematichinenoside （AR） on myocardial ischemia-reperfusion injury （MIRI） in rats and elucidate the underlying mechanism. Methods SD rats were randomly divided into six groups： sham, model, Tanshinone IIA （positive control, 16 mg/kg）, and AR （8, 16, 32 mg/kg） groups. Drug was given for seven consecutive days before the operation by ig method. Animal MIRI model was established by ligation of left anterior descending coronary artery （LAD）. Rats were sacrificed after 40 min ischemia and 120 min reperfusion. TNF-α, IL-1 t, and IL-6 in serum were measured. Myocardial infarct rate and cardiomyocyte apoptosis rate in MIRI rats were observed by TTC staining and flow cytometry, respectively. Western blotting was used to detect the expression of Bcl-2, Bax, TNF-α, and Caspase-3 in myocardial tissue. Results Compared with model group, AR at 8, 16 and 32 mg/kg reduced the TNF-α, IL-1β, and IL-6 in serum, myocardial infarct rate, and cardiomyocyte apoptosis rate. AR could up-regulate Bcl-2 and down-regulate protein expression levels of Bax, TNF-a and Caspase-3, and the differences were significant （P 〈 0.05, 0.01）. Conclusion AR plays an important role in cardioprotection and anti-apoptosis against the ischemia and reperfusion injury in rats. The mechanism could involve in inhibition of TNF-a, regulation of Bcl-2/Bax protein balance and reduction of apoptosis induced by ischemia-reoerfusion injury.

关 键 词：灵仙新苷 心肌缺血再灌注 凋亡 肿瘤坏死因子-α(TNF-α) BCL-2 BAX 

分 类 号：R965[医药卫生—药理学]