线粒体ATP敏感性钾离子通道开放剂对冠心病大鼠血管内皮损伤的影响及相关机制研究  

Effects of Mitochondrial ATP-sensitive Potassium Channel Openers on Vascular Endothelial Injury in Rats with Coronary Heart Disease

作　　者：伊加提·司马义 帕合热丁·努尔麦麦提 阿布都乃比·麦麦提艾力[1] Yijiati·Simayi;Pahereding·Nuermaimaiti;Abudunaibi·Maimaitiaili(First Affiliated Hospital of Xinjiang Medical University,Urumchi 830000,Xinjiang,China)

机构地区：[1]新疆医科大学第一附属医院,乌鲁木齐830000

出　　处：《中西医结合心脑血管病杂志》2022年第22期4093-4098,共6页Chinese Journal of Integrative Medicine on Cardio-Cerebrovascular Disease

基　　金：国家自然科学基金资助项目(No.82060907);新疆维吾尔自治区自然科学基金资助项目(No.2022D01C236)。

摘　　要：目的探究线粒体ATP敏感性钾离子通道(mito-KATP)开放剂对冠心病模型大鼠血管内皮损伤的影响及作用机制。方法30只雄性无特定病原体(SPF)级SD大鼠随机分为3组:对照组、模型组和二氮嗪组,每组10只。模型组和二氮嗪组采用高脂饮食饲养+腹腔注射脑垂体后叶素制备冠心病大鼠模型,其中,二氮嗪组制备模型后给予3 mg/kg二氮嗪灌胃治疗,对照组及模型组给予等体积生理盐水灌胃,连续给药14 d。酶联免疫吸附实验(ELISA)检测大鼠血清肿瘤坏死因子-α(TNF-α)、白细胞介素-1β(IL-1β)、白细胞介素-6(IL-6)炎性因子表达;检测血清总胆固醇(TC)、三酰甘油(TG)、低密度脂蛋白胆固醇(LDL-C)、高密度脂蛋白胆固醇(HDL-C)等血脂指标水平及血管紧张素Ⅱ(AngⅡ)、非对称性二甲基精氨酸(ADMA)等血管内皮损伤标志物水平;比较各组大鼠血管内皮细胞功能、心功能及心肌细胞病理情况;多重逆转录聚合酶链式反应(RT-PCR)实验和蛋白质免疫印迹法(Western Blot)检测大鼠心肌组织成纤维细胞生长因子2(FGF-2)、血管内皮生长因子(VEGF)等血管生成因子mRNA和蛋白表达量。结果与对照组比较,模型组及二氮嗪组大鼠血清TNF-α、IL-1β、IL-6水平明显升高(P<0.05),TC、TG、LDL-C水平明显升高(P<0.05),HDL-C水平明显降低(P<0.05),AngⅡ、ADMA水平明显升高(P<0.05),左室收缩压(LVSP)、左心室压力变化最大上升速率(+dp/dt_(max))、左心室压力最大下降速率(-dp/dt_(max))、冠状动脉血流量(CF)明显下降(P<0.05),心肌细胞形态紊乱,不同程度炎症浸润表现,心肌组织中FGF-2、VEGF基因及蛋白表达水平明显降低(P<0.05)。与模型组比较,二氮嗪组大鼠血清TNF-α、IL-1β、IL-6水平及TC、TG、LDL-C水平降低(P<0.05),HDL-C水平升高(P<0.05),AngⅡ、ADMA水平明显下降(P<0.05),LVSP、+dp/dt_(max)、-dp/dt_(max)、CF升高(P<0.05),心肌细胞水肿缓解,炎症状态减轻,心肌组织中FGF-2、VObjective To investigate and analyze the effect of mitochondrial ATP-sensitive potassium ion channel(mitoKATP)opener on vascular endothelial injury in rats with coronary heart disease and the mechanism of action.Methods Thirty male specific pathogen-free(SPF)SD rats were randomly divided into 3 groups:control group,model group,and diazoxide group,with 10 rats in each group.The rats in model group and diazoxide group were given high-fat diet and intraperitoneal injection of pituitrin to prepare coronary heart disease rat model.The rats in diazoxide group were given 3 mg/kg diazoxide lavage treatment,the rats in control group and model group was given saline by lavage,continuously for 14 days.Enzyme-linked immunosorbent assay(ELISA)was used to detect the expression of inflammatory cytokines including tumor necrosis factor-α(TNF-α),interleukin-1β(IL-1β),and interleukin-6(IL-6)in serum of rats.Serum total cholesterol(TC),triacylglycerol(TG),low density lipoprotein cholesterol(LDL-C),high density lipoprotein cholesterol(HDL-C),angiotensinⅡ(AngⅡ),and asymmetric dimethyl arginine(ADMA)were detected.Vascular endothelial cell function,cardiac function,and myocardial cell pathology were compared between each group.The mRNA and protein expressions of angiogenic factors,such as fibroblast growth factor 2(FGF-2)and vascular endothelial growth factor(VEGF)were detected by reverse transcription-polymerase chain reaction(RT-PCR)and Western Blot.Results Compared with control group,serum TNF-α,IL-1β,and IL-6 inflammatory factor levels were significantly increased(P<0.05),TC,TG,and LDL-C levels were significantly increased too(P<0.05),HDL-C level was significantly decreased(P<0.05),AngⅡ,ADMA levels were increased(P<0.05),left ventricular systolic pressure(LVSP),+dp/dt_(max),-dp/dt_(max),and CF were significantly decreased(P<0.05),myocardial cell morphology was disorder,the expression levels of FGF-2,VEGF gene and protein in myocardial tissue were significantly increased(P<0.05)in model group and diazoxide group.Compared

关 键 词：冠心病 血管内皮损伤 线粒体ATP敏感性钾离子通道开放剂 实验研究 

分 类 号：R541.4[医药卫生—心血管疾病]