| 引用本文: | 张石在,王毅,马瑞莲,刘晶,刘天龙.黄芪多糖抑制TGF-β1和Nox4/Akt/mTOR信号通路保护心肌重构的作用研究[J].中国现代应用药学,2021,38(24):3108-3114. |
| ZHANG Shizai,WANG Yi,MA Ruilian,LIU Jing,LIU Tianlong.Study on Effect of Astragalus Polysaccharide in Protecting Cardiac Remodeling by Inhibiting TGF-β1 and Nox4/Akt/mTOR Signal Pathway[J].Chin J Mod Appl Pharm(中国现代应用药学),2021,38(24):3108-3114. |
|
| 摘要: |
| 目的 研究黄芪多糖（Astragalus polysaccharide，APS）对心肌重构的保护作用及机制。方法 通过主动脉弓缩窄（transverse aortic constriction，TAC）构建心肌重构小鼠模型并使用APS进行干预。利用心脏超声成像系统，心肌组织麦胚凝集素染色、天狼星红染色及Real-time PCR评价APS对心肌重构小鼠模型的保护作用。Western blotting检测心肌组织中Nox4、TGF-β1、mTOR及Akt的表达水平，探讨APS保护心肌重构的机制。结果 TAC手术4周后，TAC组小鼠左心室舒张末期后壁厚度（left ventricular end-diastolic posterior wall dimension，LVPWd）较空白对照组显著增加（P<0.01），左心室收缩功能显著下降，而APS+TAC组小鼠LVPWd较TAC组显著降低（P<0.05），左心室收缩功能明显改善。APS对TAC诱导的小鼠心体比和心胫比增加具有显著的保护作用（P<0.001）。心肌组织病理染色结果显示，TAC组小鼠心肌细胞肥大水平和心肌纤维化水平较空白对照组小鼠显著增加（P<0.01），而APS对TAC诱导的心肌细胞肥大和纤维化具有显著的保护作用（P<0.01或P<0.05）。与空白对照组比较，TAC组小鼠心肌组织中心钠素和脑钠肽的表达水平显著升高（P<0.001），而APS对此有显著的抑制作用（P<0.01或P<0.05）。进一步研究发现，APS干预对TAC诱导的Nox4、TGF-β1、mTOR及p-Akt在心肌组织中的表达具有显著的抑制作用。结论 APS能够通过抑制TGF-β1和Nox4/Akt/mTOR信号通路发挥对心肌重构小鼠模型的保护作用。 |
| 关键词: 黄芪多糖 心肌重构 保护作用 TGF-β1信号通路 Nox4/Akt/mTOR信号通路 |
| DOI：10.13748/j.cnki.issn1007-7693.2021.24.010 |
| 分类号:R285.5 |
| 基金项目:国家自然科学基金项目（81960048）；内蒙古自治区自然科学基金（2019BS08003）；内蒙古医科大学百万工程项目[YKD2018KJBW（LH）026]；内蒙古医科大学附属医院博士启动金计划项目（NYFYBS202114） |
|
| Study on Effect of Astragalus Polysaccharide in Protecting Cardiac Remodeling by Inhibiting TGF-β1 and Nox4/Akt/mTOR Signal Pathway |
|
ZHANG Shizai1, WANG Yi2, MA Ruilian2, LIU Jing2, LIU Tianlong2
|
|
1.Department of Basic Medicine, Ordos Institute of Technology, Ordos 017000, China;2.Department of Pharmacy, Affiliated Hospital of Inner Mongolia Medical University, Hohhot 010030, China
|
| Abstract: |
| OBJECTIVE To study the protective effect and mechanism of Astragalus polysaccharide(APS) on cardiac remodeling. METHODS Mouse cardiac remodeling model prepared by transverse aortic constriction(TAC) was treated with APS. The protective effect of APS on cardiac remodeling was evaluated by echocardiography, wheat germ agglutinin staining and picrosirius red staining of myocardial tissue and Real-time PCR. Expression level of Nox4, TGF-β1, mTOR and Akt was detected by Western blotting to illustrate the mechanism of APS on cardiac remodeling. RESULTS After TAC for 4 weeks, compared to blank control group, left ventricular end-diastolic posterior wall dimension(LVPWd) was significantly increased(P<0.01), the contractile function of the left ventricle decreased significantly, and the LVPWd of the mice in the APS+TAC group was significantly lower than that in the TAC group(P<0.05), and the contractile function of the left ventricle was significantly improved. APS treatment could inhibit TAC-induced increase in ratio of heart weight to body weight and heart weight to tibial length(P<0.001). The pathological staining results of myocardial tissue showed that a significant increase in cardiac hypertrophy and fibrosis was found in mice in TAC group compared with blank control group(P<0.01), while APS treatment had a significantly protective effect on TAC-induced cardiac hypertrophy and fibrosis(P<0.01 or P<0.05). Compared to blank control group, a significant increased expression level of atrial natriuretic peptide and brain natriuretic peptide were observed in heart of model mice(P<0.001), which was inhibited in APS-treated mice(P<0.01 or P<0.05). Further study showed that APS had a significant inhibitive effect on TAC-induced expression of Nox4, TGF-β1, mTOR and p-Akt in myocardial tissue. CONCLUSION APS protect TAC-induced cardiac remodeling via inhibiting TGF-β1 and Nox4/Akt/mTOR signal pathway. |
| Key words: Astragalus polysaccharide cardiac remodeling protective effect TGF-β1 signal pathway Nox4/Akt/mTOR signal pathway |
