线粒体ATP敏感性钾离子通道开放剂对大鼠冠状动脉硬化斑块及血脂代谢的影响  

Effects of mitochondrial ATP sensitive potassium channel opener on coronary atherosclerotic plaque and lipid metabolism in rats

作　　者：彭颖静 刘丽敏[1] 姚健[1] 张金盈 PENG Yingjing;LIU Limin;YAO Jian;ZHANG Jinying(Department of Cardiology,Second Affiliated Hospital of Shenyang Medical College,Shenyang,Liaoning 110016,China)

机构地区：[1]沈阳医学院附属第二医院心血管内科,110016

出　　处：《重庆医学》2022年第9期1441-1447,共7页Chongqing medicine

基　　金：国家自然科学基金项目(81570274)。

摘　　要：目的探讨线粒体ATP敏感性钾离子通道开放剂通过调控过氧化物酶体增殖物激活受体γ(PPARγ)通路对大鼠冠状动脉硬化斑块及血脂代谢的影响。方法将50只大鼠分为对照组、模型组、二氮嗪组、PPARγ抑制剂(GW9662)组、二氮嗪+GW9662组,除对照组外,其余各组采用高脂饲料喂养、腹腔注射维生素D_(3)建立冠状动脉粥样硬化性心脏病大鼠模型。检测血脂指标、血清炎症因子水平,油红O染色观察主动脉弓血管壁脂质沉淀情况,透射电镜观察主动脉弓内皮细胞线粒体损伤情况,RT-qPCR法和Western blot法检测主动脉弓PPARγ、核因子-κB p65(NF-κB p65)mRNA和PPARγ、NF-κB p65、NF-κB p-p65蛋白表达量。结果(1)血脂指标及炎症因子:与对照组比较,模型组、GW9662组、二氮嗪组、二氮嗪+GW9662组血脂指标及血清炎症因子水平均较高,其中GW9662组>模型组>二氮嗪+GW9662组>二氮嗪组(P<0.05)。(2)主动脉弓血管壁脂质沉淀:对照组无脂质沉淀,模型组有大量成片脂滴沉淀,GW9662组较模型组脂滴沉淀更多,二氮嗪组较模型组脂滴沉淀减少,而二氮嗪+GW9662组较二氮嗪组脂滴沉淀增多。(3)主动脉弓血管内皮细胞中线粒体损伤:对照组线粒体双层膜结构清晰、完整;模型组线粒体双层膜结构不连续,线粒体嵴断裂或模糊,呈现肿胀和空泡化现象;GW9662组较模型组线粒体嵴断裂明显,部分仅留残端,肿胀和空泡化严重;二氮嗪组较模型组线粒体损伤减轻;而二氮嗪+GW9662组较二氮嗪组线粒体损伤稍加重。(4)主动脉弓PPARγ、NF-κB mRNA和蛋白及NF-κB p-p65蛋白表达水平:与对照组比较,模型组、GW9662组、二氮嗪组、二氮嗪+GW9662组PPARγmRNA和蛋白相对表达量降低,其中GW9662组<模型组<二氮嗪+GW9662组<二氮嗪组(P<0.05);与对照组比较,模型组、GW9662组、二氮嗪组、二氮嗪+GW9662 NF-κB p-p65蛋白相对表达量升高,其中GW9662组>模型组>二氮嗪+GW9662组>�Objective To investigate the effect of mitochondrial ATP sensitive potassium channel opener on coronary atherosclerotic plaque and lipid metabolism by regulating peroxisome proliferator activated receptor gamma(PPARγ)pathway in rats.Methods Fifty rats were divided into the control group,model group,diazoxide group,PPARγinhibitor(GW9662)group and diazoxide+GW9662 group.Except for the control group,the other groups were fed with high-fat diet and VD_(3) was intraperitoneally injected to construct the rat model of atherosclerotic coronary heart disease.The blood lipid indexes and the levels of serum cytokines were detected.The lipid precipitation in the blood vessel wall of the aortic arch was observed by the oil red staining.The epithelial mitochondrial injury situation of the aortic arch was observed by the transmission electron microscope.The PPARγ,nuclear factor-κB p65(NF-κB p65)mRNA and PPARγ,NF-κB p65,NF-κB p-p65 protein expression levels in aortic arch were detected by RT-qPCR and Western blot.Results(1)The blood lipid indicators and inflammatory factors:compared with the control group,the levels of blood lipid indicators and serum inflammatory factors were higher in the model group,GW9662 group,diazoxide group and diazoxide+GW9662 group,among which GW9662 group>model group>diazoxide+GW9662 group>diazoxide group(P<0.05).(2)The lipid precipitation in the vessel wall of the aortic arch:there was no lipid precipitation in the control group,and there were a large number of lipid droplets in the model group.The GW9662 group had more lipid droplets than the model group.The diazoxide group had less lipid droplets than the model group.The diazoxide+GW9662 group had more lipid droplet precipitation than the diazoxide group.(3)The mitochondrial damage in endothelial cells of the aortic arch:the structure of the mitochondrial double-layer membrane in the control group was clear and complete;the structure of the mitochondrial double-layer membrane in the model group was discontinuous,with broken or blurred crista

关 键 词：冠状动脉粥样硬化 血脂代谢 线粒体ATP敏感性钾离子通道开放剂 过氧化物酶体增殖物激活受体Γ 

分 类 号：R541.4[医药卫生—心血管疾病]