肉苁蓉苯乙醇总苷对大鼠肝星状细胞TGF-β1/Smad信号通路表达的影响

doi:10.3969/j.issn.1004-616x.2016.05.008

癌变·畸变·突变 ›› 2016, Vol. 28 ›› Issue (5): 372-376.doi: 10.3969/j.issn.1004-616x.2016.05.008

肉苁蓉苯乙醇总苷对大鼠肝星状细胞TGF-β1/Smad信号通路表达的影响

由淑萍¹, 赵军², 马龙¹, 张石蕾¹, 刘涛¹

1. 新疆医科大学公共卫生学院卫生毒理学教研室, 新疆乌鲁木齐 830011;
2. 新疆维吾尔自治区药物研究所, 新疆乌鲁木齐 830004

收稿日期:2016-04-13 修回日期:2016-06-23 出版日期:2016-09-30 发布日期:2016-09-30
通讯作者: 刘涛,E-mail:xjmult@163.com E-mail:xjmult@163.com
作者简介:由淑萍,E-mail:youshupin@163.com
基金资助:
国家自然科学基金项目（81260624）

Effect of phenylethanol glycosides on the TGF-β1/Smad signaling pathway in the rat HSC-T6 hepatic stellate cells

YOU Shuping¹, ZHAO Jun², MA Long¹, ZHANG Shilei¹, LIU Tao¹

1. Department of Toxicology, College of Public Health, Xinjiang Medical University, Urumqi 830011;
2. Xinjiang Uygur Autonomous Region Institute of Materia Medica, Urumqi 830004, Xinjiang, China

Received:2016-04-13 Revised:2016-06-23 Online:2016-09-30 Published:2016-09-30

摘要/Abstract

摘要： 目的：探讨肉苁蓉苯乙醇总苷（CPhGs）对转化生长因子β1（TGF-β1）介导的大鼠肝星状细胞（HSC-T6）增殖活化作用及对TGF-β1/Smad信号通路表达的影响。方法：试验分为正常对照组、5 ng/mL TGF-β1刺激的HSC-T6模型组、5 ng/mL TGF-β1+不同终浓度（25、50、75和100 μg/mL）CPhGs给药组，另设只加DMEM培养液的空白组。体外培养HSC-T6细胞，通过四甲基偶氮唑盐法（MTT）检测细胞的增殖；LDH比色法测定CPhGs的细胞毒性；采用荧光定量PCR（qPCR）检测Smad2、Smad3和Smad7 mRNA的表达；采用Western blot法检测Smad2、Smad3、p-Smad2、p-Smad3和Smad7蛋白的表达。结果：与正常对照组比较，TGF-β1模型组显著促进了HSC-T6细胞的增殖，而50~100 μg/mL的CPhGs可以抑制TGF-β1诱导的HSC-T6细胞的增殖（P<0.05），且25~100 μg/mL的CPhGs对HSC-T6无明显细胞毒性作用；25~100 μg/mL CPhGs均可抑制Smad2和Smad3 mRNA和蛋白水平的表达，且明显抑制Smad2和Smad3蛋白的磷酸化水平，促进Smad7 mRNA和蛋白的表达，差异均具有统计学意义（P<0.05或P<0.01）。结论：CPhGs的抗肝纤维化作用可能与其阻断TGF-β1/Smad通路进而阻断HSC-T6细胞的活化和增殖有关。

关键词: 肉苁蓉苯乙醇总苷, 转化生长因子β1, 肝星状细胞, 肝纤维化

Abstract: OBJECTIVE: To investigate the effect of phenylethanol glycosides from cistanchetubulosa(CPhGs) on cell proliferation and activation of TGF-β1-induced hepatic stellate cells (HSC-T6). METHODS: HSC-T6 cells were cultivated with CPhGs in different concentrations (25,50,75,100 μg/mL). After the cells were stimulated with TGF-β1,cell activity and drug cytotoxicity were determined by MTT and LDH,respectively. Smad2,Smad3,Smad7 mRNA and Smad2,Smad3,p-Smad2,p-Smad3,Smad7 protein expressions were assayed by qPCR and Western blot. RESULTS: CPhGs at 50-100 μg/mL concentrations effectively inhibited TGF-β1-mediated cell proliferation (P<0.05) and CPhGs at 25-100 μg/mL concentrations did not induce significant cytotoxicity. CPhGs at 25-100 μg/mL concentrations,inhibited Smad2 and Smad3 mRNA and protein levels,as well as the phosphorylation levels of Smad2 and Smad3 proteins,but increased Smad7 mRNA and protein expression significantly on HSC-T6 (P<0.05 or P<0.01). CONCLUSION: CPhGs demonstrated the protective effect against hepatic fibrosis. The mechanism of this process could involve interference with the TGF-β1/Smad signaling pathway,and inhibition of activation and proliferation of HSC-T6.

Key words: phenylethanol glycosides from cistanchetubulosa, transforming growth factor-β1, hepatic stellate cells, hepatic fibrosis

中图分类号:

R961.1

由淑萍, 赵军, 马龙, 张石蕾, 刘涛. 肉苁蓉苯乙醇总苷对大鼠肝星状细胞TGF-β1/Smad信号通路表达的影响[J]. 癌变·畸变·突变, 2016, 28(5): 372-376.

YOU Shuping, ZHAO Jun, MA Long, ZHANG Shilei, LIU Tao. Effect of phenylethanol glycosides on the TGF-β1/Smad signaling pathway in the rat HSC-T6 hepatic stellate cells[J]. Carcinogenesis, Teratogenesis & Mutagenesis, 2016, 28(5): 372-376.

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肉苁蓉苯乙醇总苷对大鼠肝星状细胞TGF-β1/Smad信号通路表达的影响

Effect of phenylethanol glycosides on the TGF-β1/Smad signaling pathway in the rat HSC-T6 hepatic stellate cells

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