摘要
目的:探讨水蛭素联合阿托伐他汀对急性心肌梗死大鼠血管内皮功能的影响,并阐明其可能的作用机制。方法:50只大鼠随机分为假手术组、模型组、水蛭素组、阿托伐他汀组和联合组,每组10只。采用结扎左冠状动脉前降支的方法建立急性心肌梗死大鼠模型。水蛭素组、阿托伐他汀组和联合组大鼠分别灌胃给予水蛭素50 U·kg^-1、阿托伐他汀10 mg·kg^-1及水蛭素50 U·kg^-1+阿托伐他汀10 mg·kg^-1,假手术组和模型组大鼠给予等量生理盐水,连续给药4周。采用2,3,5-三苯基氯化四氮唑(TTC)染色法测定大鼠心肌梗死面积,计算心肌梗死面积百分比,采用HE染色观察大鼠心肌组织病理形态表现,Western blotting法检测大鼠心肌组织中血管细胞黏附分子1(VCAM-1)和细胞间黏附分子1(ICAM-1)蛋白表达水平,酶联免疫吸附测定(ELISA)法检测大鼠血清中内皮素1(ET-1)、血管性血友病因子(vWF)、一氧化氮(NO)、肿瘤坏死因子α(TNF-α)和白细胞介素6(IL-6)水平。结果:与假手术组比较,模型组大鼠心肌细胞排列紊乱,部分细胞不完整,心肌坏死程度严重,有炎性细胞浸润;与模型组比较,水蛭素组、阿托伐他汀组和联合组大鼠心肌细胞排列较整齐,心肌坏死程度明显改善,炎性细胞浸润情况明显减轻。与假手术组比较,模型组大鼠心肌组织中VCAM-1和ICAM-1蛋白表达水平明显升高(P<0.05),血清中ET-1、vWF、TNF-α和IL-6水平明显升高(P<0.05),NO水平明显降低(P<0.05);与模型组比较,水蛭素组、阿托伐他汀组和联合组大鼠心肌梗死面积百分比明显减小(P<0.05),心肌组织中VCAM-1和ICAM-1蛋白表达水平明显降低(P<0.05),血清中ET-1、vWF、TNF-α和IL-6水平明显降低(P<0.05),NO水平明显升高(P<0.05);与水蛭素组和阿托伐他汀组比较,联合组大鼠心肌梗死面积百分比明显减小(P<0.05),心肌组织中VCAM-1和ICAM-1蛋白表达水平明显降低(P<0.05),血清中ET-1、vWF、
Objective:To investigate the effects of hirudin combined with atorvastatin on the vascular endothelial function in the rats with acute myocardial infarction,and to elucidate the possible mechanisms.Methods:A total of 50 rats were randomly divided into sham operation group,model group,hirudin group,atorvastatin group and combination group(n=10).The rat models with acute myocardial infarction were established by ligating the left anterior descending coronary artery.The rats in hirudin group,atorvastatin group and combination group were given 50 U·kg^-1 hirudin,10 mg·kg^-1 atorvastatin,50 U·kg^-1 hirudin and 10 mg·kg^-1 atorvastatin,respectively;while the rats in sham operation group and model group were given normal saline for 4 weeks.The 2,3,5-Triphenyte-trazoliumchloride(TTC)staining method was used to determine the myocardial infarction areas of the rats,and the percentage of myocardial infarction area was calculated.HE staining was used to observe the pathomorphology of myocardium tissue of the rats.Western blotting method was used to detect the protein expression levels of vascular cell adhesion molecule-1(VCAM-1)and intercellular adhesion molecule-1(ICAM-1)proteins in myocardium tissue of the rats.ELISA was used to determine the levels of endothelin-1(ET-1),von Willebrand factor(vWF),nitric oxide(NO),tumor necrosis factor(TNF-α)and interleukin-6(IL-6)in serum of the rats.Results:Compared with sham operation group,the arrangement of myocardial cells in model group were disordered,some cells were incomplete,myocardial necrosis was serious,and inflammatory cell infiltration was found.Compared with model group,the arrangement of myocardial cells in hirudin group,atorvastatin group and combination group was in order,the myocardial necrosis was improved,and the inflammatory cell infiltraton was alleviated.Compared with sham operation group,the expression levels of VCAM-1 and ICAM-1 proteins in myocardium tissue of the rats in model group were significantly increased(P<0.05),the levels of ET-1,vWF,TNF-αand IL-
作者
成颖
杨静
饶莉
薛强
胡杰
付乐
张巧月
CHENG Ying;YANG Jing;RAO Li;XUE Qiang;HU Jie;FU Le;ZHANG Qiaoyue(Department of Emergency,Tangshan Workers’Hospital,Hebei Province,Tangshan 063000,China;Department of Rheumatology,Tangshan Workers’Hospital,Hebei Province,Tangshan 063000,China;Department of Pharmacy,Tangshan Workers’Hospital,Hebei Province,Tangshan 063000,China)
出处
《吉林大学学报（医学版）》
CAS
CSCD
北大核心
2021年第1期139-144,共6页
Journal of Jilin University：Medicine Edition
基金
河北省卫健委医学科学项目(2021)。
关键词
水蛭素
阿托伐他汀
急性心肌梗死
血管内皮功能
hirudin
atorvastatin
acute myocardial infarction
vascular endothelial function
