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氨甲酰化促红细胞生成素对慢性心力衰竭大鼠心肌细胞凋亡及cleaved Caspase-3蛋白表达的影响 被引量:1

Effects of Carbamylated Erythropoietin on the Apoptosis and Cleaved Caspase-3 Protein in Rat with Chronic Heart Failure
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摘要 目的观察氨甲酰化促红细胞生成素(CEPO)对慢性心力衰竭(CHF)大鼠心功能、心肌细胞凋亡及半胱氨酸天冬氨酸蛋白酶-3(Caspase-3)蛋白活化表达的影响。方法将30只雄性成年SD大鼠随机分为假手术(Sham)组(n=10)、CEPO组(n=10)和对照(Control)组(n=10),采用腹主动脉缩窄术制作慢性心力衰竭模型,术后第8周CEPO组开始经腹腔注射50μg/kg CEPO,3次/周,连续4周;Sham组、Control组同期经腹腔注射等量0.9%氯化钠溶液。术后第8周、12周行心脏彩超检测大鼠心功能。术后第12周末取大鼠心肌组织切片采用HE染色法观察心肌组织细胞形态;采用原味缺口末端标记(TUNEL)法检测心肌细胞凋亡及计算凋亡指数(AI);采用Western blot印迹法检测心肌活化型Caspase-3(cleaved Caspase-3)蛋白表达水平。结果与假手术组相比,建模大鼠术后第8周时出现心室肥厚及左室射血分数(LVEF)减退;CEPO组干预4周后左室射血分数较Control组明显升高(P<0.05),收缩末期室间隔厚度(IVSs)、收缩末期左心室后壁厚度(LVPWs)、舒张末期室间隔厚度(IVSd)、舒张末期左心室后壁厚度(LVPWd)明显降低(P<0.05)。与Control组比较,CEPO组AI值显著降低[(23.87±1.45)%vs(30.15±0.67)%,P<0.05],cleaved Caspase-3表达水平(0.489 1±0.029 1)明显减少(P<0.01)。结论 CEPO可通过抑制凋亡关键酶Caspase-3的活化,显著减少cleaved Caspase-3蛋白的表达水平,减少心肌细胞凋亡以改善心功能。 Objective To observe the effects of cardiomyocytes carbamylated erythropoietin(CEPO)on the cardiac function,the apoptosis of cardiomyocytes,protein cleaved cysteine-containing aspartate-specific proteases(cleaved Caspase-3)expression in rats with chronic heart failure(CHF).Methods Firstly,30 male adult SD rats were randomly divided into three groups,sham-operated(Sham)group(n =10),CEPO group(n =10)and control(Control)group(n =10).CHF model was built by abdominal aortic coarctation.After postoperative eight weeks,rats in CEPO group received 50μg/kg CEPO by intraperitoneal injection 3 times/week for 4weeks.The rats in Sham group and Control group received equal normal saline.Respectively,after 8 weeks and 12 weeks,cardiac function was observed with echocardiography.After 12 weeks,all rats were sacrificed,cell morphology was observed by HE staining.The myocardial apoptosis and calculated apoptosis index(AI);was observed Myocardial cleaved Caspase-3 protein expression was observed by western blot.Results Echocardiography showed CHF rats had ventricular hypertrophy and heart failure in8 weeks.CEPO intervention after 4 weeks compared with Control group,left ventricular ejection fraction(LVEF)was significantly higher(P〈0.05),systolic interventricular septum thickness(IVSs),end-systolic left ventricular posterior wall thickness(LVPWs),diastolic interventricular septum thickness(IVSd),left ventricular end-diastolic wall thickness(LVPWd)was significantly lower(P〈0.05).AI in CEPO group was significantly lower than that in Control group[(23.87±1.45)% vs(30.15±0.67)%,P〈0.05].The cleaved Caspase-3 OD values significantly decreased in CEPO group(0.489 1±0.029 1)with Control group(P〈0.01).Conclusion CEPO can improve heart function in rats with CHF the cardiomyocyte apoptosis,by down-ragulating the express of cleaved Caspase-3 protein.
出处 《中西医结合心脑血管病杂志》 2017年第16期1974-1978,共5页 Chinese Journal of Integrative Medicine on Cardio-Cerebrovascular Disease
基金 广东省科技厅基金项目(No.2013B022000103)
关键词 心力衰竭 氨甲酰化促红细胞生成素 心肌凋亡 活化型Caspase-3蛋白 heart failure carbamylated erythropoietin cardiac apoptosis cleaved Caspase-3 protein
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