| RhoE通过抑制Smad3信号通路的激活改善AngⅡ诱导的心肌纤维化 |
| 投稿时间：2024-09-15 修订日期：2024-11-17 点此下载全文 |
| 引用本文：酉鹏华,何晓敏,张碧雪,程征.RhoE通过抑制Smad3信号通路的激活改善AngⅡ诱导的心肌纤维化[J].医学研究杂志,2025,54(4):45-51 |
| DOI：
10.11969/j.issn.1673-548X.2025.04.010 |
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| 基金项目:国家自然科学基金资助项目(面上项目)(82070282)；西安市科技计划项目(24YXYJ0136) |
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| 中文摘要:目的 探讨RhoE过表达在血管紧张素Ⅱ诱导的心肌纤维化中的保护性作用及机制。方法 体外培养原代心肌细胞,使用血管紧张素Ⅱ诱导的心肌纤维化的模型,根据分组,转染含有携带m-RhoE 过表达腺病毒,过表达RhoE,通过原代心肌细胞中 α-SMA 的免疫荧光的检测及Smad3表达分布的免疫荧光检测,Western blot法检测原代细胞中 RhoE、GAPDH、α-SMA、Smad3、p-Smad3蛋白表达水平。结果 Ang Ⅱ 干预原代心肌细胞,Western blot法检测结果显示,与对照相比较,AngⅡ组中,p-Smad3及α-SMA表达水平增高,RhoE表达水平下降(P＜0.05)。转染RhoE过表达腺病毒后,通过 Western blot法检测结果显示,与对照相比较,AngⅡ组α-SMA表达水平增高(P＜0.05)；与AngⅡ组比较,Ang Ⅱ+Ad-RhoE组α-SMA表达水平明显降低(P＜0.05)。免疫荧光检测显示,与对照相比较,AngⅡ组α-SMA荧光强度增加(P＜0.05)；与AngⅡ组比较,Ang Ⅱ+Ad-RhoE组α-SMA荧光强度明显降低(P＜0.05)。RhoE基因过表达对TGF-β1/Smad3通路的影响。Western blot法检测结果显示,与对照组比较,AngⅡ组p-Smad3/Smad3比值升高(P＜0.05)；与AngⅡ组比较,Ang Ⅱ+Ad-RhoE组p-Smad3/Smad3比值明显下降(P＜0.05)；免疫荧光核转位显示,与对照组比较,AngⅡ组心肌细胞核内的红色荧光显著增多(P＜0.05)；与AngⅡ组比较,Ang Ⅱ+Ad-RhoE组心肌细胞核内的红色荧光显著减少(P＜0.05)。结论 AngⅡ诱导心肌纤维化过程中伴随着TGF-β1/Smad3信号通路激活,RhoE可通过抑制TGF-β1/Smad3信号通路,抑制Ang2诱导的心肌纤维化。 |
| 中文关键词:血管紧张素Ⅱ 心室重塑 心肌纤维化 RhoE |
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| RhoE Improves AngⅡ-Induced Myocardial Fibrosis by Inhibiting Activation of Smad3 Signaling Pathway. |
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| Abstract:Objective To investigate the protective effect and mechanism of RhoE overexpression in angiotensin Ⅱ-induced myocardial fibrosis. Methods Primary cardiomyocytes were cultured in vitro using angiotensin Ⅱ-induced myocardial fibrosis model, and transfected with M-RhoE-carrying overexpressing adenovirus and overexpressing RhoE according to subgroup. α-SMA and Smad3 expression distribution in primary cardiomyocytes were detected by immunofluorescence. The protein expression levels of RhoE, GAPDH, α-SMA, Smad3 and p-Smad3 in primary cells were detected by Western blotting. Results Ang Ⅱ interferes with primary cardiomyocytes. Western-blot analysis showed that compared with the control group,the expression levels of p-Smad3 and α-SMA in AngⅡ group were increased, while the expression levels of RhoE were decreased(P<0.05). After transfection of RhoE overexpressing adenovirus, Western blot results showed that the α-SMA expression level in AngⅡ group was increased compared with that in the control group (P<0.05). Compared with AngⅡ group α-SMA expression level in AngⅡ+Ad-RhoE group was significantly decreased (P<0.05). Immunofluorescence detection showed that the α-SMA fluorescence intensity in AngⅡ group was increased compared with that in control group (P<0.05). Compared with AngⅡ group α-SMA fluorescence intensity in AngⅡ +Ad-RhoE group was significantly decreased (P<0.05). Effects of overexpression of RhoE gene on TGF-β1/Smad3 pathway. Western blot results showed that compared with the control group, the p-Smad3 /Smad3 ratio in AngⅡ group was increased (P<0.05). Compared with AngⅡ group, the p-Smad3/Smad3 ratio in AngⅡ +Ad-RhoE group was significantly decreased (P<0.05).Immunofluorescence nuclear translocation showed that compared with the control group, the red fluorescence in myocardial nucleus of AngⅡ group was significantly increased (P<0.05). Compared with AngⅡ group, the red fluorescence in myocardial nucleus of AngⅡ +Ad-RhoE group was significantly decreased (P<0.05).Conclusion The process of AngⅡ-induced myocardial fibrosis is accompanied by the activation of TGF-β1/Smad3 signaling pathway, and RhoE can inhibit AngⅡ-induced myocardial fibrosis by inhibiting TGF-β1/Smad3 signaling pathway. |
| keywords:Angiotensin Ⅱ Ventricular remodeling Myocardial fibrosis RhoE |
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