机构地区:[1]西安交通大学第二附属医院,陕西西安710004
出 处:《辽宁中医药大学学报》2020年第6期29-33,共5页Journal of Liaoning University of Traditional Chinese Medicine
基 金:陕西省自然科学基础研究计划面上项目(2018JM7087)。
摘 要:目的从细胞凋亡途径研究穿心莲内酯对高脂血症大鼠心肌缺血再灌注损伤(Myocardial ischemia reperfusion injury,MI/RI)的作用。方法 60只SD大鼠在适应性喂养2周后按照随机数字法分为假手术组、模型组、银杏内酯B干预组以及穿心莲内酯低、中和高剂量组,每组10只,除假手术组外,其余5组给予高脂肪饲料8周构建高脂血症模型,造模成功后所有大鼠均接受2周相应药物预防治疗,2周后行心肌缺血再灌注损伤术,于术后24 h,收集血液和血脂,检测血脂甘油三酯(Triglyceride,TG)、总胆固醇(Total cholesterol,TC)、低密度脂蛋白胆固醇(Low density lipoprotein cholesterol,LDL-C)和高密度脂蛋白胆固醇(High density lipoprotein cholesterol,HDL-C)、超声心动左心室射血分数(Left ventricular ejection fraction,LVEF)和左心室短轴缩短率(Left ventricular fractional shortening,LVFS)、炎性因子白细胞介素-10(Interleukinin-10,IL-10)、肿瘤坏死因子-α(Tumor necrosis factor-α,TNF-α)、细胞间黏附分子-1(Intercellular adhesion molecules,ICAM-1)水平,HE染色观察心肌组织变化,蛋白质印迹法(Western blot)和实时荧光定量聚合酶链式反应(real-time quantitative Polymerase Chain Reaction,QT-PCR)法检测心肌组织B淋巴细胞瘤-2基因相关X蛋白(B-cell lymphoma-2 Associated X Protein,Bax)和B淋巴细胞瘤-2基因(B-cell lymphoma-2,Bcl-2)蛋白及mRNA水平。结果与假手术组相比,模型组TG、TC、LDL-C、HDL-C、IL-10、TNF-α、ICAM、LVEF和LVFS明显升高(P<0.05),相较于模型组,穿心莲内酯3个剂量组和银杏内酯B组上述指标明显降低(P<0.05);HE染色可见假手术组细胞结构完整,而模型组则出现心肌结构紊乱,穿心莲内酯3个剂量组和银杏内酯B干预组明显好转;与假手术组相比,模型组Bax蛋白及mRNA表达明显增加(P<0.05),Bcl-2明显降低(P<0.05),相较于模型组,穿心莲内酯3个剂量组和银杏内酯B干预组Bax蛋白及mRNA表达明显降低(P<0.05),Bcl-2明Objective To investigate the effect of andrographolide on myocardial ischemia reperfusion injury(MI/RI)in rats with hyperlipidemia. Methods 60 SD rats were randomly divided into the sham group,model group,ginkgolides B intervention group and andrographolide low,medium and high dose groups,n=10,except the sham group,the others five groups were given high-fat diet for 8 weeks to construct a hyperlipidemia rat model. After successful built the model,all rats received 2 weeks drug treatment,and 2 weeks later,MI/RI surgery was performed and after 24 hours,collect the blood to detected triglyceride(TG),total cholesterol(TC),low density lipoprotein cholesterol(LDL-C),high density lipoprotein cholesterol,left ventricular ejection fraction(LVEF),left ventricular fractional shortening(LVFS),interleukinin-10(IL-10),tumor necrosis factor-α(TNF-α),intercellular adhesion molecules(ICAM-1)levels,HE staining to observe liver pathology,Western blot,and QT-PCR detected the Bax,Bcl-2 protein and mRNA expression. Results Compared with the sham group,TG,TC,LDL-C,HDL-C,IL-10,TNF-α,ICAM,LVEF and LVFS were significantly increased in the model group(P<0.05),compared with the model group. those above indexes in the three dose andrographolide treatment groups and ginkgolide B group were significantly lower(P<0.05);HE staining showed that the sham group showed structural integrity and is smooth,while the model group showed myocardial structural disorder,compared with the sham group,the expression of Bax protein and mRNA in the model group was significantly increased(P<0.05)and Bcl-2 was significantly decreased(P<0.05),compared with the model group. The Bax protein and mRNA were significantly decreased in the three doses andrographolide and ginkgolides B group(P<0.05),and Bcl-2 was significantly increased(P<0.05). Conclusion Andrographolide can protect myocardial ischemia-reperfusion injury in rats with hyperlipidemia. The reason may be related to its ability to lower blood lipids,regulate inflammation and inhibit cardiomyocyte apoptosis.
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