首页|川芎嗪衍生物影响肝星状细胞增殖的作用机制研究

川芎嗪衍生物影响肝星状细胞增殖的作用机制研究

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目的 研究川芎嗪衍生物H168抑制肝星状细胞(HSC-T6)增殖的机制.方法 MTS比色法观察H168对HSC-T6细胞增殖的影响;流式细胞仪检测H168对细胞周期的影响;应用Western blot和Real time PCR方法观察H168对p21/p27蛋白及mRNA表达的影响.结果 MTS结果显示H168具有明显的抑制HSC-T6增殖的作用,随着药物浓度的增大,对HSC-T6增殖的抑制作用逐渐增强,呈现量效关系.流式细胞周期检测发现H168作用24 h后,G0/G1期细胞增多,S期及G2/M期细胞减少;Western blot结果显示H168通过促进p21/p27蛋白表达抑制细胞的增殖;进一步采用Real time PCR研究发现,H168能够从mRNA水平促进p21/p27表达.结论 H168能抑制HSC-T6细胞的增殖,这主要是通过促进p21/p27蛋白和mRNA的表达而抑制HSC-T6细胞增殖.
Effect of tetramethylpyrazine derivative H168 on hepatic stellate cells proliferation and its possible mechanism
Aim To observe the effect of tetrameth-ylpyrazine derivative H168 on hepatic stellate cells (HSC) proliferation and its possible mechanism. Methods MTS was used to detect the effect of tetram-ethylpyrazine derivative H168 on HSC-T6 proliferation. Cell cycle was measured by flow cytometry(FCM) a-nalysis with PI dual staining. Western blotting and Real time PCR were used to detect the protein and mRNA expression of p21/p27. Results Tetramethylpyrazine derivative H168 inhibited the proliferation of HSC-T6 obviously. With the increase of drug concentration , the potential efficacy on inhibition of HSC-T6 proliferation showed a dose-dependent manner. Cycle detected by flow cytometry of the drug showed the cells accumulated in G0/G1 phase, and reduced in S and G2/M pha-ses. FCM detection found tetramethylpyrazine derivative H168 with the dose-effect promotion of apoptosis on HSC. Western blot results showed the tetramethylpyrazine derivative H168 inhibited HSC-T6 proliferation by promoting p21/p27 protein expression. Further use of Real time PCR found that ligustrazine derivative H168 promoted expression of p21/p27 mRNA. Conclusion H168 can inhibit HSC-T6 proliferation mainly through promoting the protein and mRNA expression of P21/p27.

hepatic fibrosistetramethylpyrazine derivativeHSC-T6proliferationcell cyclemolecular mechanism

张雪娇、倪春艳、张峰、陆茵、郑仕中

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药学院,临床药理学教研室,南京,210029

江苏省中药药效与安全性评价重点实验室,江苏,南京,210046

肝纤维化 川芎嗪衍生物 HSC-T6 增殖 细胞周期 分子机制

国家自然科学基金教育部高等学校博士学科点专项科研基金江苏省针灸学重点实验室开放课题江苏省自然科学基金江苏省"六大人才高峰"项目江苏高校优势学科建设工程资助项目

3087342420103237110010KJA200801BK200845609-B-010ysxk-2010

2012

中国药理学通报
中国药理学会

中国药理学通报

CSTPCDCSCD北大核心
影响因子:1.54
ISSN:1001-1978
年,卷(期):2012.28(6)
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