黄芪对阿霉素诱导扩张型心肌病大鼠心肌细胞凋亡的影响

发布时间：2018-08-11 14:29

【摘要】：目的：明确黄芪对扩张型心肌病(DCM)大鼠心肌细胞凋亡的影响；观察黄芪对DCM大鼠心功能的改善作用；揭示黄芪防治DCM的可能作用机制。方法：阿霉素1mg/kg/只腹腔注射建立DCM大鼠模型,每周2次,连续12次,观察2周。造模后将95只大鼠分为正常组(n=14)、模型组(n=21)、培哚普利组(n=20)、美托洛尔组(n=20)、黄芪组(n=20)。培哚普利组每日予培哚普利片3mg/kg/只灌胃,1次/日。美托洛尔组每日予美托洛尔片50mg/kg/只灌胃,2次/日。黄芪组每日予黄芪颗粒剂3.5mg/kg/只灌胃,1次/日。正常组和模型组每日予蒸馏水灌胃,灌胃量与治疗组相同,1次/日。所有组别治疗时间为8周。治疗后对各组行心脏彩超检测左室舒张末内径(LVIDd)、左室收缩末内径(LVIDs)、左室射血分数(LVEF)、左室短轴缩短率(FS), ELISA法检测血清BNP,左室心肌组织HE病理观察,RT-PCR和Western-blot法分别测定大鼠心肌组织Bax、Bcl-2、Fas1、Fas、Caspase3 mRNA及蛋白表达。结果：1.心脏彩超结果：与模型组比较,正常组、各治疗组LVIDd、LVIDs减少,LVEF与FS增加,P值0.05。黄芪组与培哚普利组、美托洛尔组比较,LVIDd、LVIDs、FSP值0.05,LVEF P值0.05。2.1R清BNP：与模型组比较,正常组、各治疗组血清BNP降低,P值0.05。黄芪组与培哚普利组、美托洛尔组比较,P0.05。3.左室心肌HE染色：正常组心肌细胞形态正常,肌纤维排列整齐,结构完整；可见圆形或类圆形的细胞核；细胞间隙无水肿,胞质与血管丰富。模型组心肌细胞肿胀明显；肌纤维排列紊乱、断裂,心肌纤维化明显；细胞核固缩、变形或消失；细胞间隙水肿、增宽,部分颗粒、空泡样变性,血管扩张充血,可见单核及淋巴细胞浸润。各治疗组心肌HE染色结果较模型组明显改善,心肌纤维化程度减轻,细胞间隙水肿、空泡变性好转。4.心肌组织Bax、Bcl-2、Fas1、Fas、Caspase3 mRNA水平：与模型组比较,正常组、各治疗组Bax mRNA减低、Bcl-2 mRNA增加,P值0.05；Fas1、Fas mRNA减低,P值0.05：Caspase3 mRNA减低,P值0.05。黄芪组与培哚普利组、美托洛尔组比较,Bax、 Bcl-2、Fas1、Fas、Caspase3 mRNA P值0.05。5.心肌组织Bcl-2、Fas、Caspase3蛋白水平：与模型组比较,正常组、各治疗组Bcl-2蛋白水平增高,Fas、Caspase3蛋白水平均降低,P值0.05。黄芪组与培哚普利组、美托洛尔组比较,Bcl-2、Fas、Caspase3蛋白P值0.05。结论：1.黄芪能够缩小DCM大鼠心腔内径,提高射血分数,增强心肌收缩力,降低血清BNP水平,保护受损心肌组织。2.黄芪能够调控DCM大鼠心肌组织Bax、Bcl-2、Fas1、 Fas Caspase3 mRNA和蛋白表达。3.黄芪可能有抑制心肌细胞凋亡的作用,从而对DCM产生有益影响。
[Abstract]:AIM: To investigate the effect of Astragalus membranaceus on cardiomyocyte apoptosis in rats with dilated cardiomyopathy (DCM), to observe the effect of Astragalus membranaceus on cardiac function in DCM rats, and to reveal the possible mechanism of Astragalus membranaceus in preventing and treating DCM. The normal group (n = 14), model group (n = 21), perindopril group (n = 20), metoprolol group (n = 20), Astragalus group (n = 20). The perindopril group was given perindopril tablets 3 mg / kg per day, once a day. The metoprolol group was given metoprolol tablets 50 mg / kg per day, twice a day. The Astragalus group was given Astragalus granules 3.5 mg / kg per day, once a day. All groups were treated for 8 weeks. After treatment, left ventricular end-diastolic diameter (LVIDd), left ventricular end-systolic diameter (LVIDs), left ventricular ejection fraction (LVEF), left ventricular short-axis shortening rate (FS), serum BNP and left ventricular myocardial tissue HE disease were detected by echocardiography. The expression of Bax, Bcl-2, Fas-1, Fas, Caspase-3 mRNA and protein in myocardium of rats were detected by RT-PCR and Western-blot respectively.Results:1. Cardiac color Doppler ultrasonography results: Compared with model group, LVIDd, LVIDs decreased, LVEF and FS increased, P value was 0.05. Compared with perindopril group, Astragalus group, metoprolol group, LVIDd, LVIDs, FSP value was 0.0.0. 5, LVEF P value 0.05.2.1R BNP: Compared with the model group, the normal group, the treatment group, the serum BNP decreased, P value 0.05.Astragalus group and perindopril group, metoprolol group, P 0.05.3. Left ventricular myocardial HE staining: normal myocardial cells, myofibrils arranged neatly, complete structure; visible circular or quasi-circular nuclei; intercellular space; No edema, cytoplasm and blood vessel were abundant. Cardiac myocytes in model group swelled significantly; myocardial fibers arranged disorderly, ruptured, myocardial fibrosis was obvious; nucleus pyknosis, deformation or disappearance; intercellular space edema, widening, some granules, vacuole-like degeneration, vascular dilatation and congestion, monocyte and lymphocyte infiltration could be seen. Myocardial tissue Bax, Bcl-2, Fas 1, Fas, Caspase 3 mRNA levels: Compared with the model group, the normal group, the treatment group, Bax mRNA decreased, Bcl-2 mRNA increased, P value 0.05; Fas 1, Fas mRNA decreased, P value 0.05: Caspase 3 mRNA decreased, P value 0.05. Bax, Bcl-2, Fas 1, Fas, Caspase 3 mRNA P value 0.05.5. Myocardial Bcl-2, Fas, Caspase 3 protein levels: Compared with model group, normal group, the treatment group Bcl-2 protein levels increased, Fas, Caspase 3 protein levels were decreased, P value 0.05. Astragalus group compared with perindopril group, metoprolol group, Bcl-2, Fas, Caspase 3 protein levels The P value of pase3 protein was 0.05. Conclusion: 1. Astragalus membranaceus can reduce the diameter of heart cavity, increase ejection fraction, enhance myocardial contractility, decrease serum BNP level and protect damaged myocardial tissue in DCM rats. 2. Astragalus membranaceus can regulate the expression of Bax, Bcl-2, Fas1, Fas Caspase3 mRNA and protein in myocardial tissue of DCM rats. 3. Astragalus membranaceus may inhibit myocardial cell apoptosis. It has a beneficial effect on DCM.
【学位授予单位】：南京中医药大学
【学位级别】：硕士
【学位授予年份】：2016
【分类号】：R259

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