引用本文:黄文坛,伍秋霞,彭小梅,王浩宇,曾莹晖,刘园园,韦俏宇,曾剑峰,冯海云,钟 键.TM5275对TGF-β1诱导的人肾小球系膜细胞增殖 凋亡和细胞外基质的影响[J].中国临床新医学,2019,12(7):714-719.
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TM5275对TGF-β1诱导的人肾小球系膜细胞增殖 凋亡和细胞外基质的影响
黄文坛,伍秋霞,彭小梅,王浩宇,曾莹晖,刘园园,韦俏宇,曾剑峰,冯海云,钟 键
530021 南宁,广西壮族自治区人民医院肾内科
摘要:
[摘要] 目的 探讨TM5275对转化生长因子β1(TGF-β1)诱导的人肾小球系膜细胞增殖、凋亡和细胞外基质的影响。方法 体外培养人肾小球系膜细胞,实验分为对照组、模型组和干预组。采用四甲基偶氮唑蓝(MTT)法检测系膜细胞的增殖率,流式细胞术法检测细胞凋亡,Western blot法检测纤溶酶原激活物抑制剂-1(PAI-1)、a-平滑肌肌动蛋白(a-SMA)、纤维黏连蛋白(fibronectin,FN)、Ⅳ型胶原蛋白(Collagen-Ⅳ)、B淋巴细胞瘤基因相关x蛋白(Bax)、B淋巴细胞瘤基因-2(Bcl-2)和半胱天冬酶-3(caspase-3)蛋白的表达水平。结果 TM5275可抑制TGF-β1诱导的系膜细胞增殖,并促进其凋亡。与对照组比较,模型组TGF-β1可诱导系膜细胞的PAI-1、a-SMA蛋白及细胞外基质FN、Collagen-Ⅳ蛋白的表达水平显著升高(P<0.05),TM5275干预可抑制其表达。与对照组及模型组比较,干预组促凋亡蛋白Bax、caspase-3表达显著增加(P<0.05),但抑凋亡蛋白Bcl-2无明显表达,在三组中未能检测出。结论 TM5275可抑制TGF-β1诱导的系膜细胞增殖和细胞外基质的表达,同时通过诱导促凋亡蛋白的表达,促进异常增殖的系膜细胞凋亡,具有治疗系膜增生性肾小球肾炎的潜在前景。
关键词:  纤溶酶原激活物抑制剂-1  人肾小球系膜细胞  凋亡  细胞外基质  纤维化
DOI:10.3969/j.issn.1674-3806.2019.07.04
分类号:R 692
基金项目:国家自然科学基金资助项目(编号:81460150);广西卫健委科研课题(编号:Z2006147)
Effects of TM5275 on proliferation,apoptosis and extracellular matrix of human mesangial cells induced by TGF-β1
HUANG Wen-tan, WU Qiu-xia, PENG Xiao-mei, et al.
Departement of Nephrology, the People′s Hospital of Guangxi Zhuang Autonomous Region, Nanning 530021, China
Abstract:
[Abstract] Objective To study the effects of TM5275 on the proliferation, apoptosis and extracellular matrix of human mesangial cells induced by transforming growth factor beta 1(TGF-β1). Methods Human mesangial cells were cultured in vitro and were divided into control group, model group and intervention group. The proliferation rate of human mesangial cells was detected by methyl thiazolyl tetrazolium(MTT) assay, and apoptosis was detected by flow cytometry, and the expression levels of PAI-1, a-SMA, fibronectin(FN), Collagen-Ⅳ, Bax, Bcl-2 and caspase-3 proteins were detected by Western blot. Results TM5275 inhibited the proliferation of human mesangial cells induced by TGF-β1 and promoted apoptosis of the cells. Compared with those in the control group, the expressions of PAI-1, a-SMA, extracellular matrix FN and Collagen-Ⅳ induced by TGF-β1 in human mesangial cells in the model group were significantly increased(P<0.05), and TM5275 inhibited those expressions. Compared with those in the control group and the model group, the expressions of the pro-apoptotic proteins Bax and caspase-3 in the intervention group were significantly increased(P<0.05), but the anti-apoptotic protein Bcl-2 was not expressed and could not be detected in the three groups. Conclusion TM5275 can inhibit the proliferation of human mesangial cells and the expression of extracellular matrix induced by TGF-β1. At the same time,TM5275 can promote the apoptosis of abnormal proliferation of human mesangial cells by inducing the expression of pro-apoptotic proteins. It has a potential prospect in the treatment of mesangial proliferative glomerulonephritis.
Key words:  Plasminogen activator inhibitor-1(PAI-1)  Human mesangial cell  Apoptosis  Extracellular matrix  Fibrosis