[1]李岚岚 谢赛阳 邓伟.tirzepatide对AngⅡ诱导的心肌细胞肥大的抑制作用及机制研究[J].心血管病学进展,2024,(9):844.[doi:10.16806/j.cnki.issn.1004-3934.2024.09.017]
　LI Lanlan,XIE Saiyang,DENG Wei.Inhibitory Effect of Tirzepatide on Ang-induced Cardiomyocyte Hypertrophy and Study of the Mechanism[J].Advances in Cardiovascular Diseases,2024,(9):844.[doi:10.16806/j.cnki.issn.1004-3934.2024.09.017]
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tirzepatide对AngⅡ诱导的心肌细胞肥大的抑制作用及机制研究()
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《心血管病学进展》[ISSN:51-1187/R/CN:1004-3934]

卷:
期数:
2024年9期
页码:
844
栏目:
论著
出版日期:
2024-09-25

文章信息/Info

Title:
Inhibitory Effect of Tirzepatide on Ang-induced Cardiomyocyte Hypertrophy and Study of the Mechanism
作者:
李岚岚 谢赛阳 邓伟
(武汉大学人民医院心血管内科 代谢与相关慢病湖北重点实验室,湖北 武汉 430060)
Author(s):
LI Lanlan; XIE Saiyang; DENG Wei
(Department of Cardiology,Renmin Hospital of Wuhan University,Hubei Key Laboratory of Metabolism and Related Chronic Diseases,Wuhan 430060,Hubei,China)
关键词:
tirzepatide; 血管紧张素Ⅱ; 心肌细胞肥大; 细胞自噬
Keywords:
Tirzepatide; Angiotensin ; Cardiomyocyte hypertrophy; Cell autophagy
DOI:
10.16806/j.cnki.issn.1004-3934.2024.09.017
摘要:
目的 探讨tirzepatide（TZP）对血管紧张素Ⅱ（Ang Ⅱ）诱导新生大鼠心肌细胞肥大的影响及机制研究。方法 分离新生大鼠心肌细胞并进行体外培养，采用Ang Ⅱ （1 umol/L）刺激心肌细胞24 h建立心肌细胞肥大模型，使用TZP（100 nmol/L）和AngⅡ（1 umol/L）共同孵育新生大鼠心肌细胞24 h。实验随机分为4组：正常对照组、TZP组、AngⅡ组和AngⅡ+TZP组。采用鬼笔环肽染色评估单个心肌细胞肥大程度；TUNEL检测心肌细胞凋亡情况；CCK-8法检测心肌细胞活力；2,7-二氯二氢荧光素二乙酸酯荧光探针检测活性氧水平；逆转录聚合酶链反应检测新生大鼠心肌细胞中心房利尿钠肽、脑利尿钠肽、β-肌球蛋白重链、B细胞淋巴瘤-2相关X蛋白（Bax）、B细胞淋巴瘤-2（Bcl-2）、NADPH氧化酶2（Nox）2、Nox4和NADPH氧化酶活化蛋白1（NOXA2）、超氧化物歧化酶 2（SOD2）、醌氧化还原酶1（NQO1）和谷胱甘肽过氧化物酶（GSH-Px）的mRNA表达水平；Western blot检测新生大鼠心肌细胞细胞中脑利尿钠肽、Bax、Bcl-2、SOD2、NQO1和GSH-Px蛋白质的表达水平。此外，逆转录聚合酶链反应和Western blot检测各组心肌细胞中的Beclin-1和p62的mRNA和蛋白质表达水平。结果 TZP可显著降低AngⅡ诱导的心肌细胞肥大标志物和凋亡标志物的蛋白质及mRNA表达水平的升高，下调促氧化因子Nox2、Nox4和NOXA2的mRNA表达水平，促进抗氧化因子SOD2、NQO1和GSH-Px的mRNA表达水平。以上作用与正常对照组比较差异均有统计学意义（P＜0.05）。同时，Western blot和自噬小体检测证实了TZP主要通过抑制细胞内自噬途径来拮抗AngⅡ诱导的心肌细胞肥大。结论 TZP可缓解AngⅡ诱导的心肌细胞肥大，并通过抑制自噬途径改善AngⅡ诱导的心肌细胞肥大作用。
Abstract:
Objective To investigate the effect and mechanism of tirzepatide (TZP) in angiotensin Ⅱ (AngⅡ)-induced neonatal rat cardiomyocyte hypertrophy. Methods Neonatal rat cardiomyocytes were isolated and cultured in vitro,AngⅡ (1 umol/L) was used to stimulate cardiomyocytes for 24 h to establish a cardiomyocyte hypertrophy model,and eonatal rat cardiomyocytes were co-incubated using TZP (100 nmol/L) and AngⅡ (1 umol/L) for 24 h. The experiment will be randomly divided into four groups: control group,TZP group,AngⅡ group,and AngⅡ+TZP group. Phalloidin staining was used to assess the degree of hypertrophy of individual cardiomyocytes;TUNEL staining was used to detect cardiomyocyte apoptosis;CCK -8 was used to detect cardiomyocyte activity;DCFH-DA fluorescent probe was used to detect the level of reactive oxygen species (ROS) ;and reverse transcription-polymerase chain reaction was used to detect the mRNA levels of atrial natriuretic peptide ,brain natriuretic peptide,and β-myosin heavy chain ( β-MHC),B-cell lymphoma-2 associated X protein(Bax),B-cell lymphoma-2(Bcl-2),reduced nicotinamide adenine dinucleotide phosphate oxidase(Nox)2,Nox4,reduced nicotinamide adenine dinucleotide phosphate oxidase activator 2 (NOXA2),superoxide dismutase 2 (SOD2),quinone oxidoreductase 1(NQO1) and glutathione peroxidase(GSH-Px). The expression levels of brain natriuretic peptide,Bax,Bcl-2,SOD2,NQO1 and GSH-Px proteins were detected by Western blot in neonatal rat cardiomyocyte. In addition, reverse transcription-polymerase chain reaction and Western blot were performed to detect the mRNA and protein expression levels of Beclin-1 and p62 in cardiomyocytes of each group. Results TZP can significantly reduce the increase in protein and mRNA expression levels of cardiomyocyte hypertrophy markers and apoptosis markers induced by Ang Ⅱ,down-regulate the mRNA expression levels of pro-oxidant factors Nox2, Nox4 and NOXA2,and promote the antioxidant factors SOD2,NQO1 and GSH-Px mRNA expression levels. Compared with the control group,the above effects were statistically significant(P＜0.05). Meanwhile,Western blot and autophagosome assay confirmed that TZP antagonized AngⅡ-induced cardiomyocyte hypertrophy mainly by inhibiting intracellular autophagy pathway. Conclusion TZP can alleviate AngⅡ-induced cardiomyocyte hypertrophy and improve the effect of AngⅡ-induced cardiomyocyte hypertrophy by inhibiting autophagy

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更新日期/Last Update: 2024-10-17