沙库巴曲缬沙坦钠片通过NF2/Mst1信号通路抑制细胞凋亡改善心肌梗死大鼠心肌纤维化  

Sacubitril Valsartan inhibited apoptosis through NF2/Mst1 signaling pathway to improve myocardial fibrosis in rats after myocardial infarction

作　　者：向长铁 刘佳丽 张爱民 吴倩 聂连桂 刘茂军[1] 杨军[1] XIANG Chang-Tie;LIU Jia-Li;ZHANG Ai-Min(Department of Cardiology,the First Affiliated Hospital of South China University,Hengyang 421001,Hunan,China)

机构地区：[1]南华大学附属第一医院心内科,湖南衡阳421001 [2]常德市石门县人民医院

出　　处：《中国老年学杂志》2022年第8期1927-1931,共5页Chinese Journal of Gerontology

基　　金：国家自然科学基金(No.81870230);湖南省自然科学基金项目(No.2020JJ5505)。

摘　　要：目的观察沙库巴曲缬沙坦钠片(诺欣妥,Lcz696)对异丙肾上腺素(Iso)诱导的心肌梗死大鼠心肌纤维化及对细胞凋亡和神经纤维蛋白(NF)2/哺乳动物不育系20样激酶(Mst)1通路的影响。方法40只SD雄性大鼠随机分成4组:对照组(Control组)、模型组(Iso组)、Lcz696干预组(Iso+Lcz696组)和缬沙坦(Vdt)干预组(Iso+Vdt组)。采用腹腔注射Iso50 mg/(kg·d):2 d的方法建立急性心肌梗死大鼠模型,以心电图及血浆肌钙蛋白水平确定模型构建是否成功。Iso+Lcz696组给予Lcz69660 mg/(kg·d)溶解于蒸馏水后灌胃,Iso+Vdt组给予Vdt 30 mg/(kg·d)溶解于等量的蒸馏水后灌胃,Iso组和Control组则同时给予等量的蒸馏水灌胃。干预4 w后处死大鼠,以Masson染色检测心肌胶原沉积,以Western印迹法检测半胱天冬酶(Caspase)9、B淋巴细胞瘤(Bcl)-2、NF2、Mst1蛋白表达水平。结果与Control组相比,其余3组大鼠心电图Ⅱ导联T波高耸,ST段弓背向上抬高,血浆肌钙蛋白显著升高,提示急性心肌梗死模型构建成功。Masson染色检测显示Iso组心肌胶原沉积显著增加,而Iso+Lcz696组心肌胶原沉积显著减少,而Iso+Lcz696组与Iso+Vdt组相比,心肌胶原沉积亦显著减少。Iso组大鼠心肌Caspase9、NF2、Mst1蛋白表达显著增加而Bcl-2蛋白表达显著减少(均P<0.05);而与Iso组相比,Iso+Lcz696组Caspase9、NF2、Mst1蛋白表达显著降低而Bcl-2表达显著升高(均P<0.05),Iso+Vdt Caspase9、NF2、Mst1蛋白表达显著降低(均P<0.05),而Bcl-2蛋白表达不明显,但与Iso+Vdt组相比,Iso+Lcz696组NF2、Mst1蛋白减少更明显(均P<0.05)。结论与Vdt相比,Lcz696能更有效地通过抑制心肌细胞凋亡改善Iso诱导的心肌梗死大鼠心肌纤维化,其机制可能与抑制NF2/Mst1通路有关。Objective To observe the effects of Sacubitril Valsartan(Lcz696)on myocardial fibrosis induced by isoproterenol(Iso)induced myocardial infarction in rats and on apoptosis and the NF2/Mst1 pathway.Methods Fourty male SD rats were randomly divided into 4 groups:Control group,model group(Iso group),Lcz696 intervention group(Lcz696+Iso group)and valsartan(Vdt)intervention group(Vdt+Iso group).The rat model of acute myocardial infarction was established by intraperitoneal injection of Iso 50 mg/(kg·d):for 2 days,and the success of the model was determined by electrocardiogram and plasma troponin T levels.Iso+Lcz696 group was given Lcz69660 mg/(kg·d)dissolved in distilled water and gavage,Iso+Vdt group was given Vdt 30 mg/(kg·d)dissolved in the same amount of distilled water and gavage,Iso and Control groups were given the same amount of distilled water.Rats were anesthetized to death after 4 weeks of intervention,myocardial collagen deposition was detected by Masson staining,the protein expression levels of Caspase9,bcl-2,NF2 and Mst1 were detected by Western blotting.Results Compared with the Control group,the electrocardiogramⅡlead T wave of rats in the other three groups was higher,the ST segment was dorsal and elevated,and the plasma troponin T was significantly increased,suggested the establishment of acute myocardial infarction model was successful.Masson staining showed that myocardial collagen deposition was significantly increased in Iso group,myocardial collagen deposition was significantly reduced in Iso+Lcz696 group.Compared with Iso+Vdt group,myocardial collagen deposition was also significantly reduced in Iso+Lcz696 group.The protein expression of Caspase9,NF2 and Mst1 in Iso group were significantly increased,while the protein expression of Bcl-2 was significantly decreased.Compared with the Iso group,the protein expression of Caspase9,NF2 and Mst1 in the Iso+Lcz696 group were significantly decreased,while the protein expression of Bcl-2 was significantly increased.Compared with the Iso group,the p

关 键 词：诺欣妥 异丙肾上腺素 心肌细胞凋亡 心肌纤维化 NF2/Mst1 

分 类 号：R542.2[医药卫生—心血管疾病]