川芎多糖对大鼠心肌缺血再灌注损伤的影响

Effect of Chuanxiong polysaccharide on myocardial ischemia-reperfusion injury in rats

目的:研究川芎多糖对大鼠心肌缺血再灌注损伤(MIRI)的影响及机制。方法:将144只大鼠随机分为假手术组、模型组、维拉帕米组和川芎多糖低、中、高剂量组,造模前14 d开始1次/d灌胃给药。通过夹闭冠状动脉左前降支构建MIRI大鼠模型,再灌注2 h后,通过超声心动图检测大鼠心功能,计算心肌梗死面积,HE、TUNEL染色观察心肌组织病变和细胞凋亡,ELISA法检测肿瘤坏死因子-α(TNF-α)、白细胞介素-1β(IL-1β)、白细胞介素-6(IL-6)含量,分光光度法检测丙二醛(MDA)含量和超氧化物歧化酶(SOD)、过氧化氢酶(CAT)活性,Western blot法检测高迁移率族蛋白B1(HMGB1)表达。结果:与模型组比较,维拉帕米组和川芎多糖低、中、高剂量组心功能指标明显改善(均P<0.05);心肌组织病变和细胞凋亡明显改善,病理评分和凋亡指数降低(均P<0.05);心肌组织TNF-α、IL-1β、IL-6、MDA含量降低,SOD、CAT活性升高,HMGB1表达量降低(均P<0.05)。川芎多糖上述效应呈现剂量依赖性。结论:川芎多糖具有改善MIRI大鼠心功能、减轻心肌组织病变和细胞凋亡的作用,其机制可能与抑制氧化应激、炎症反应以及抑制HMGB1表达有关。

Objective:To investigate the effect and mechanism of Chuanxiong polysaccharide on myocardial ischemia-reperfusion injury(MIRI)in rats.Methods:144 rats were randomly divided into sham operation group,model group,verapamil hydrochloride group and Chuanxiong polysaccharide low dose,medium dose,high dose groups,and the drugs were given once a day from 14 d before modeling.The rat model with MIRI was constructed by clamping the left anterior descending coronary artery.2 h after reperfusion,the cardiac function of the rats was detected by echocardiography.The myocardial infarction area was calculated.The myocardial histopathological changes and cell apoptosis were detected by HE and TUNEL staining.The content of malondialdehyde(MDA),superoxide dismutase(SOD)and catalase(CAT)were determined by spectrophotometry.The expression of high mobility group protein B1(HMGB1)was detected by Western blot.Results:Compared with the model group,the cardiac function in verapamil hydrochloride group and Chuanxiong polysaccharide low,medium,high dose groups was significantly improved(all P<0.05).The pathological changes of myocardial tissue and apoptosis were significantly improved,the pathological score and apoptosis index were decreased(all P<0.05).The content of TNF-α,IL-1β,IL-6,MDA in myocardial tissue were decreased,while the activity of SOD,CAT were increased,the expression of HMGB1 was decreased(all P<0.05).The above effects of Chuanxiong polysaccharide showed dose dependence.Conclusion:Chuanxiong polysaccharide can improve the cardiac function of MIRI rats,alleviate myocardial tissue pathological changes and cell apoptosis,which may be related to the inhibition of oxidative stress,inflammation and expression of HMGB1.