沙库巴曲缬沙坦钠对心力衰竭大鼠心肌内质网应激的影响  

Effect of sacubitril valsartan sodium on endoplasmic reticulum stress of myocardial cells in heart failure rats

作　　者：张志敏 马丽群 魏星 李慧杰[1] 路军 王国位 周圣华[1] ZHANG Zhimin;MA Liqun;WEI Xing;LI Huijie;LU Jun;WANG Guowei;ZHOU Shenghua(Department of Cardiology,General Hospital of Xinjiang Military Region,Urumqi 830000,China;Health Department,General Hospital of Xinjiang Military Region)

机构地区：[1]新疆军区总医院心内科,乌鲁木齐830000 [2]新疆军区总医院保健科

出　　处：《山西医科大学学报》2020年第11期1182-1187,共6页Journal of Shanxi Medical University

基　　金：新疆维吾尔自治区自然科学基金资助项目(2017D01C423)。

摘　　要：目的观察沙库巴曲缬沙坦钠对心衰大鼠心肌细胞内质网应激(endoplasmic reticulum stress,ERS)的影响。方法20只雄性SD大鼠,其中15只大鼠行主动脉缩窄术(transverse aortic contriction,TAC)制备心衰大鼠模型,术后随机分为TAC组、缬沙坦组、沙库巴曲缬沙坦组,每组5只;另外5只假手术大鼠为假手术组。采用颈动脉插管法检测大鼠血压、心率及左心室血流动力学指标。使用小动物超声检测大鼠心功能。通过Masson染色观察心肌胶原纤维含量的改变。ELISA检测大鼠心肌组织中氨基末端脑钠尿肽前体(brain natriuretic peptide,BNP)、可溶性肿瘤因子2抑制剂(sST2)水平。Western blot检测大鼠心肌组织中GRP78及CHOP表达变化。结果(1)与假手术组相比,TAC组大鼠平均动脉压(MAP)、平均左心室舒张末期压(LVEDP)及平均压下降最大速率(-dP/dtmax)显著升高(P<0.01),平均左心室收缩峰压(LVPP)、平均压力上升最大速率(+dP/dtmax)显著降低(P<0.01)。与TAC组相比,缬沙坦组MAP、LVEDP、-dP/dtmax明显降低(P<0.05),LVPP和+dP/dtmax明显升高(P<0.05);沙库巴曲缬沙坦组MAP、LVEDP、-dP/dtmax显著降低(P<0.01),LVPP和+dP/dtmax显著升高(P<0.05)。(2)Masson染色可见假手术组大鼠心肌组织未见明显胶原纤维增生,TAC组心肌间质纤维较多,缬沙坦组心肌间质少量胶原纤维化,沙库巴曲缬沙坦组心肌间质偶见胶原纤维。(3)TAC组BNP及sST2水平较假手术组显著升高(P<0.01);与TAC组相比,缬沙坦组BNP水平明显降低(P<0.05),沙库巴曲缬沙坦组BNP和sST2水平显著降低(P<0.01)。(4)与假手术组相比,TAC组大鼠射血分数(ejection fraction,EF)及左心室短轴率(fractional shortening,FS)显著降低(P<0.01);与TAC组相比,缬沙坦组EF及FS明显升高(P<0.05),沙库巴曲缬沙坦组EF及FS显著升高(P<0.01)。(5)与假手术组相比,TAC组心肌GRP78和CHOP蛋白表达显著增高(P<0.01);与TAC组相比,缬沙坦组GRP78和CHOP表达明显降低(P<0.05),�Objective To observe the influence of sacubitril valsartan sodium on endoplasmic reticulum stress(ERS)of myocardial tissues in heart failure rats.Methods Fifteen rats underwent transverse aortic contriction(TAC)operation,and then were randomly divided into TAC group,valsartan group and sacubitril valsartan group,with five in each group.Five sham-operated rats were defined as sham group.Carotid artery intubation method was used to detect blood pressure,heart rate and left ventricular hemodynamics.Small animal ultrasound was used to detect rat heart function.Masson staining was used to observe changes of myocardial collagen fiber content.ELISA was used to detect the levels of N-terminal pro-B-type natriuretic peptide(BNP)and soluble ST2(sST2)in rat myocardial tissue,and Western blot was used to detect the expression of glucose-regulated prontein 78(GRP78)and C/EBP-homologous protein(CHOP)in rat myocardial tissue.Results Compared with sham group,MAP,LVEDP and-d P/d t max were significantly increased in TAC group(P<0.01),while LVPP and+d P/d t max were decreased significantly(P<0.01).Compared with TAC group,MAP,LVEDP and-d P/d t max were reduced in valsartan group(P<0.05)and sacubitril valsartan group(P<0.01),while LVPP and+d P/d t max were increased in valsartan group and sacubitril valsartan group(P<0.05).There was no obvious collagen fiber in myocardium in sham group.There were more myocardial interstitial fibers in TAC group.There was a small amount of collagen fibrosis in myocardium in valsartan group and occasional collagen fibers in myocardium in sacubitril valsartan group.BNP and sST2 levels in TAC group were significantly higher than those in sham group(P<0.01).Compared with TAC group,BNP level was reduced in valsartan group(P<0.05),and BNP and sST2 levels were significantly decreased in sacubitril valsartan group(P<0.01).Compared with sham group,EF and FS were significantly decreased in TAC group(P<0.01);compared with TAC group,EF and FS were increased in valsartan group(P<0.05)and sacubitril valsartan grou

关 键 词：沙库巴曲缬沙坦钠 大鼠 心衰 内质网应激 心室重构 

分 类 号：R541.6[医药卫生—心血管疾病]