中国组织工程研究

中国组织工程研究 ›› 2010, Vol. 14 ›› Issue (37): 6877-6881.doi: 10.3969/j.issn.1673-8225.2010.37.009

• 组织构建与生物活性因子 tissue construction and bioactive factors • 上一篇    下一篇

川芎嗪干预转化生长因子β1诱导肝星状细胞结缔组织生长因子表达中p38丝裂酶原激活蛋白激酶的途径

杨建波，李孝生   

  1. 重庆医科大学附属第二医院消化内科，重庆市 400010
  • 出版日期:2010-09-10 发布日期:2010-09-10
  • 通讯作者: 李孝生，硕士，教授，硕士生导师，主要从事肝纤维化的防治研究。 LXS6896@126.com
  • 作者简介:杨建波★，男， 1982年生，汉族，四川省遂宁市人，重庆医科大学在读硕士，主要从事肝纤维化的防治研究。 sandy2007anizer@gmail.com
  • 基金资助:

    重庆市自然科学基金(2006BB5428)，重庆市卫生局科研基金(2005-A-70)，课题名称：川芎嗪对HSC的影响及CTGF信号转导的调控机制探讨。

Effect of tetramethylpyrazine on transforming growth factor beta 1-induced connective tissue growth factor expression: Role of p38 mitogen-activated protein kinase pathways in hepatic stellate cells

Yang Jian-bo, Li Xiao-sheng   

  1. Department of Gastroenterology, the Second Affiliated Hospital of Chongqing Medical University, Chongqing  400010, China
  • Online:2010-09-10 Published:2010-09-10
  • Contact: Li Xiao-sheng, Master, Professor, Master’s supervisor, Department of Gastroenterology, the Second Affiliated Hospital of Chongqing Medical University, Chongqing 400010, China LXS6896@126.com
  • About author:Yang Jian-bo★, Studying for master’s degree, Department of Gastroenterology, the Second Affiliated Hospital of Chongqing Medical University, Chongqing 400010, China sandy2007anizer@gmail.com
  • Supported by:

    the Natural Science Foundation of Chongqing, No. 2006BB5428*; the Scientific Research Foundation of Health Department of Chongqing, No. 2005-A-70*

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摘要：

背景：前期研究发现川芎嗪可通过抑制肝星状细胞的增殖和阻断Ⅰ，Ⅲ胶原的合成，下调结缔组织生长因子的表达等，发挥抗肝纤维化的作用，但具体机制尚不清楚。
目的：观察川芎嗪对体外培养肝星状细胞表达结缔组织生长因子的影响，以及p38丝裂酶原激活蛋白激酶(p38MAPK)信号通路在其中的作用。
方法：用5 μg/L转化生长因子β1诱导活化体外培养的肝星状细胞，用川芎嗪和p38MAPK特异阻断剂SB203580进行干预，以RT-PCR法检测结缔组织生长因子 mRNA和Ⅰ型胶原mRNA的表达，Western blot法检测磷酸化p38MAPK蛋白的表达。
结果与结论：经转化生长因子β1诱导后，肝星状细胞中结缔组织生长因子和Ⅰ型胶原mRNA表达显著增强(P < 0.01)，用川芎嗪和SB203580干预后，结缔组织生长因子和Ⅰ型胶原mRNA的表达均出现不同程度的下降。但川芎嗪和川芎嗪+SB203580混合干预对这两者的基因表达抑制作用比单独的SB203580干预更强。川芎嗪和SB203580对磷酸化p38MAPK蛋白表达也都有明显的抑制作用(P < 0.01)，但SB203580和川芎嗪+SB203580对其磷酸化蛋白表达抑制作用更明显，而SB203580与川芎嗪+SB203580无明显差异(P > 0.05)。因此，推测川芎嗪可能通过抑制转化生长因子β1诱导的结缔组织生长因子基因表达，阻断Ⅰ型胶原合成，其作用途径可能与抑制p38mapk信号通路有关，同时认为川芎嗪抗纤维化可能是多重作用靶点。

关键词: 川芎嗪, 肝星状细胞, p38丝裂酶原激活蛋白激酶, 结缔组织生长因子, 中药单体, 组织工程

Abstract:

BACKGROUND: Previous studies demonstrated that Tetramethylpyrazine can anti-hepatic fibrosis via inhibiting hepatic stellate cells proliferation, blocking the synthesis of type Ⅰ, Ⅲ collagen, as well as down-regulating the expression of connective tissue growth factor (CTGF), however, the detail mechanisms remains unclear.
OBJECTIVE: To investigate the effects of Tetramethylpyrazine on expression of CTGF and the role of p38 mitogen-activated protein kinase (p38MAPK) signal pathway in hepatic stellate cells (HSCs).
METHODS: HSCs were cultured in vitro, stimulated by transforming growth factor β1 (TGF-β1, 5 μg/L), and then, intervened by Tetramethylpyrazine and P38MAPK specific blocker SB203580. The expressions of CTGF and type Ⅰ collagen mRNA were measured by reverse transcription polymerase chain reaction. The phosphorylation of p38 MAPK was assessed by Western blotting.
RESULTS AND CONCLUSION: Compared with the control group, TGF-β1-induced CTGF and type Ⅰ collagen gene expressions were obviously increased (P < 0.01). CTGF and type Ⅰ collagen expressions appeared decreased in varying degrees after the intervened by Tetramethylpyrazine and SB203580. But the Tetramethylpyrazine and Tetramethylpyrazine + SB203580 inhibited the expression of type Ⅰ collagen and CTGF mRNA higher than that of SB203580. Tetramethylpyrazine and SB203580 also significantly inhibited the phosphorylation p38MAPK protein expression (P < 0.01). The inhibitory effects were more obviously in the SB203580 and Tetramethylpyrazine + SB203580 groups. However, the differences between the SB203580 group and Tetramethylpyrazine + SB203580 had no significance (P > 0.05). Accordingly, it is supposed that Tetramethylpyrazine inhibits TGF-β1-induced CTGF gene expression, blocks type Ⅰ collagen mRNA synthesis, and its mechanism may be related to inhibition p38 MAPK signaling pathways. The role of anti-fibrosis may be multi-target.

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