延胡索丁素对大鼠心肌梗死的保护作用及机制研究

The protective effect and mechanism of tetrahydrocoptisine on myocardial infarction in rats

目的考察延胡索丁素对心肌梗死大鼠的保护作用,并深入探讨潜在机制.方法取40只大鼠通过永久性结扎左冠状动脉前降支建立急性心肌梗死模型,将模型大鼠随机分为模型组、延胡索丁素低剂量组、延胡索丁素高剂量组及阳性对照组.另取10只健康大鼠设为假手术组.各给药组给予相应剂量药物,假手术组与模型组给予等量生理盐水.4周后,Vevo 2100系统考察大鼠心脏功能,ELISA法检测血清中心肌损伤标志物及炎症因子水平,HE法评估心肌组织病变情况,western bloting检测心肌组织中NLPR3、ASC及Caspase-1的表达水平.结果与模型组比较,延胡索丁素可明显升高左心室射血分数(LVEF)(P<0.05),有效降低左心室收缩末期容积(LVESV)及左心室舒张末期容积(LVEDV)(P<0.01,P<0.05);延胡索丁素可有效降低血清中白介素1β(IL-1β)、白介素18(IL-18)、肌钙蛋白I(cTnI)、肌酸激酶同工酶(CK-MB)与肌红蛋白(Myo)水平(P<0.01,P<0.05),减少梗死面积(P<0.05),改善心肌细胞炎症浸润及纤维化;同时还可明显下调心肌组织中NLPR3、ASC及caspase-1的蛋白表达(P<0.01,P<0.05).结论延胡索丁素可通过调控NLPR3/ASC信号通路,缓解心肌损伤、改善心脏功能,从而对心肌梗死发挥保护作用.

Objective To ivesigte the protetive ffe of rrahydrocopisine on acute myocandal infrction in nt,and then explore the potential mechanism.Methods 40 ras were randomly divided into the model group.the trtahyroopoisine low-dose group.the terahyrocopine high--dose group and the positive contreol goup.Another 10 healdhy tats were selected 2 the sham operation group.All groups were given the reluted dose of drug,and the sham operation group and the model group were given the same amount of saline.After 4 weeks.Vevo 2100 sytemn wa used to invesigte the cardic fium tion of tats.Serum levels of myocardual injury markers were dected by ELISA metbhod.Myocandial tisue leions were ewalured by HE staining,and the expression levels of NLPR3,ASC and caspase-1 in myoc ardial tsses were dected by westen bloting aay.Results When compared with the model group.trabhydrocoptisine could sigificandly inreased the left venticular ection fraction(LVEF)(P<0.05),reduced the left ventricular end-systolie volume(LVESV)and end-diastole volume(LVEDV)(P<0.01,P<0.05)。The serum levels of troponin I(cTn1)。creaine kinase ienzyme(ck-mb)and myoglobin(Myo)were efecively reduced by trahydrocopisine(P<0.01。P<0.05)。The infarcion arca were abo reduced(P<0.05),and the inaumatoary ifitatioan and fibroxis of myocardial cells were improved.Meanwhile,the protein expessions of NLPR3,ASC and caspase-1 in myocardial tisee were signific antly down-regulated by tetrabydrocoptisine(P<0.01.P<0.05)。Conclusion Tetralhydropalmutine plays a protective role in myoc irdal infirction by regulating NLPR3/ASC sipnaling pathway,to lleviate myocardial injury and improve candiac fianction.