沙库巴曲缬沙坦钠通过Bax/caspase-3信号通路抑制心肌细胞凋亡

doi:10.3969/j.issn.1000-1565.2023.06.009

摘要/Abstract

摘要： 为了探索沙库巴曲缬沙坦钠(LCZ696)抑制心衰心肌细胞凋亡的作用机制,腹腔注射盐酸阿霉素构建SD大鼠心衰模型,模型构建成功后随机分为心衰组(HF)、缬沙坦组(Val)、LCZ696低剂量组(LCZ-L)、LCZ696高剂量组(LCZ-H),空白组(Control),治疗8周后观察大鼠平均动脉压(MAP)、体质量、心率(HR)变化,检测血清中脑钠肽(BNP)、肌酸激酶同工酶(CK-MB)、肌酸肌酶(CK)、谷草转氨酶(AST)、谷丙转氨酶(ALT)含量,超声评价各组大鼠心功能改善情况;将大鼠左心室心肌组织进行 HE染色和Tunel染色;检测活化的AKT(P-AKT)、Bax、caspase-3蛋白表达.结果显示:心衰大鼠经Val及LCZ696治疗后超声显示心脏功能均有明显改善,BNP、CK-MB、CK、AST、ALT水平下降,其中LCZ-H组降低最明显;HE染色及Tunel染色显示经治疗后细胞凋亡数减少,心肌组织中P-AKT含量较HF增加,Bax、caspase-3蛋白含量较HF组降低,LCZ-H组减少最显著.综上可知,LCZ696通过抑制Bax/caspase-3信号通路抑制心肌细胞凋亡,改善心功能.

关键词: 沙库巴曲缬沙坦钠, Bax/caspase-3信号通路, 心衰, 心肌细胞凋亡

Abstract: To explore the mechanism of sacubitril valsartan sodium(LCZ696)on myocardial apoptosis with heart failure, a heart failure model of SD rats was established by intraperitoneal injection of doxorubicin. After successful model building, rats were randomly divided into HF group, valsartan group, and LCZ696 low(LCZ-L)group, LCZ696 high group(LCZ-H),and control group. After 8 weeks of treatment, the change of MAP, weight and HR were observed. The serum contents of BNP, CK-MB,CK, AST and ALT were detected. The improvement of cardiac function in each group was evaluated by ultrasound. Rat left ventricular myocardial tissue was subjected to HE and Tunel staining; the expression of- DOI:10.3969/j.issn.1000-1565.2023.06.009沙库巴曲缬沙坦钠通过Bax/caspase-3信号通路抑制心肌细胞凋亡李亚芹,刘毅,王潇伟,崔红根,康世鑫,徐占稳(河北大学附属医院心血管内科,河北保定 071000)摘要:为了探索沙库巴曲缬沙坦钠(LCZ696)抑制心衰心肌细胞凋亡的作用机制,腹腔注射盐酸阿霉素构建SD大鼠心衰模型,模型构建成功后随机分为心衰组(HF)、缬沙坦组(Val)、LCZ696低剂量组(LCZ-L)、LCZ696高剂量组(LCZ-H),空白组(Control),治疗8周后观察大鼠平均动脉压(MAP)、体质量、心率(HR)变化,检测血清中脑钠肽(BNP)、肌酸激酶同工酶(CK-MB)、肌酸肌酶(CK)、谷草转氨酶(AST)、谷丙转氨酶(ALT)含量,超声评价各组大鼠心功能改善情况;将大鼠左心室心肌组织进行 HE染色和Tunel染色;检测活化的AKT(P-AKT)、Bax、caspase-3蛋白表达.结果显示:心衰大鼠经Val及LCZ696治疗后超声显示心脏功能均有明显改善,BNP、CK-MB、CK、AST、ALT水平下降,其中LCZ-H组降低最明显;HE染色及Tunel染色显示经治疗后细胞凋亡数减少,心肌组织中P-AKT含量较HF增加,Bax、caspase-3蛋白含量较HF组降低,LCZ-H组减少最显著.综上可知,LCZ696通过抑制Bax/caspase-3信号通路抑制心肌细胞凋亡,改善心功能.关键词:沙库巴曲缬沙坦钠;Bax/caspase-3信号通路;心衰;心肌细胞凋亡中图分类号:Q952 文献标志码:A 文章编号:1000-1565(2023)06-0631-07Effect of sacubitril valsartan sodium on cardiomyocyte apoptosis by inhibiting Bax/caspase-3 pathwayLI Yaqin, LIU Yi,WANG Xiaowei, CUI Honggen,KANG Shixin,XU Zhanwen(Department of Cardiovascular Medicine, Affiliated Hospital of Hebei University, Baoding 071002,China)Abstract: To explore the mechanism of sacubitril valsartan sodium(LCZ696)on myocardial apoptosis with heart failure, a heart failure model of SD rats was established by intraperitoneal injection of doxorubicin. After successful model building, rats were randomly divided into HF group, valsartan group, and LCZ696 low(LCZ-L)group, LCZ696 high group(LCZ-H),and control group. After 8 weeks of treatment, the change of MAP, weight and HR were observed. The serum contents of BNP, CK-MB,CK, AST and ALT were detected. The improvement of cardiac function in each group was evaluated by ultrasound. Rat left ventricular myocardial tissue was subjected to HE and Tunel staining; the expression of- 收稿日期:2023-06-19 基金项目:河北省卫健委医学科学研究项目(20200203) 第一作者:李亚芹(1973—),女,河北定州人,河北大学附属医院副教授/副主任医师,主要从事冠心病、心力衰竭疾病研究.E-mail:liyqin2014@163.com 通信作者:刘毅(1988—),男,河北安国人,河北大学附属医院主治医师,主要从事冠心病、心衰诊治及介入治疗研究.E-mail:824516368@qq.com王潇伟(1988—),女,河北保定人,河北大学附属医院主治医师,主要从事冠心病及心衰治疗研究.E-mail:775723357@qq.com第6期李亚芹等:沙库巴曲缬沙坦钠通过Bax/caspase-3信号通路抑制心肌细胞凋亡P-AKT, Bax, and caspase-3 proteins was detected. The results showed that heart function improvement after valsartan and LCZ696 treatment.The BNP, CK-MB, CK, AST, and ALT levels were decreased. The most significant reduction was observed in the LCZ-H group. HE and Tunel staining showed decreased myocardial collagen content and apoptosis number after treatment. P-AKT in myocardial tissue increased compared with HF group, Bax and caspase-3 protein decreased compared with HF group, and LCZ-H decreased most significantly. The study show that LCZ696 inhibited cardiomyocyte apoptosis and improved cardiac function by inhibiting the Bax/caspase-3 signaling pathway.

Key words: sacubitril valsartan sodium, Bax/caspase-3 signaling pathway, heart failure, cardiomyocyte apoptosis

中图分类号:

Q952

李亚芹,刘毅,王潇伟,崔红根,康世鑫,徐占稳. 沙库巴曲缬沙坦钠通过Bax/caspase-3信号通路抑制心肌细胞凋亡[J]. 河北大学学报(自然科学版), 2023, 43(6): 631-637.

LI Yaqin, LIU Yi,WANG Xiaowei, CUI Honggen,KANG Shixin,XU Zhanwen. Effect of sacubitril valsartan sodium on cardiomyocyte apoptosis by inhibiting Bax/caspase-3 pathway[J]. Journal of Hebei University(Natural Science Edition), 2023, 43(6): 631-637.

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