【作者】 李孝生； 杨建波；

【Author】 LI Xiao-sheng,YANG Jian-bo, (Department of Gastroenterology,the Second Affiliated Hospital of Chongqing Medical University, Chongqing 400010,China)

【机构】 重庆医科大学附属第二医院消化内科；

【摘要】 目的:观察川芎嗪对体外培养肝星状细胞（HSC）表达结缔组织生长因子（CTGF）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 :体外培养肝星状细胞,用5ng/ml的转化生长因子-β₁（TGF-β₁）诱导肝星状细胞的活化,用川芎嗪和p38MAPK特异阻断剂SB203580进行干预,用RT-PCR法检测CTGFmRNA,Ⅰ型胶原mRNA的表达,Western blotting法检测磷酸化p38MAPK蛋白的表达结果:与空白对照组比较,TGF-β₁诱导CTGF和Ⅰ型胶原mRNA表达显著增强（p<0.01）,用川芎嗪和SB203580干预后,CTGF、Ⅰ型胶原mRNA的表达均出现不同程度的下降。但川芎嗪组和川芎嗪+SB203580混合组对这两者的基因表达抑制作用比单独的SB203580组更强。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<0.0 1）,但SB203580和川芎嗪+SB203580组对其磷酸化蛋白表达抑制更明显,且SB203580组与TMP+SB203580组无明显差异（p>0.05）。结论 :川芎嗪可抑制TGF-β1诱导的CTGF基因表达,阻断Ⅰ型胶原合成,其作用机制可能与抑制p38mapk信号通路有关。川芎嗪抗纤维化可能是多作用靶点。更多还原

【Abstract】 AIM: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(HSC). TMETHODS:hepatic stellate cells(HSC) were cultured in vitro,initially,HSC were stimulated by TGF-β1(5ng/ml).And then,cultured with TMP and P38MAPK specific blocker SB203580 intervention.The expression of CTGF and I collagen mRNA was measured by reverse transcription polymerase chain reaction.The phosphorylation of p38mapk was assessed by Western blotting. RESULTS:Compared with control group,TGF-β1-induced CTGF and typeⅠcollagen gene expression are increased(p<0.01).CTGF andⅠcollagen expression also appeared decreased in varying degrees after the effects by TMP and SB203580.But the TMP group and TMP+SB203580 inhibited the expression of typeⅠcollagen and CTGFmRNA higher than that SB203580.TMP and SB203580 on the phosphorylation P38MAPK protein expression also have significantly inhibited(p<0.01). However,TMP and TMP+SB203580group more obviously inhibited it phosphorylation.Though between the TMP group and TMP+SB203580 was no significant difference(p>0.05). CONCLUSION:TMP can inhibit TGF-β1-induced CTGF gene expression,blocking type I collagen mRNA synthesis,its mechanism may be related to inhibition p38mapk signaling pathways.The role of anti-fibrosis may be multi-target.更多还原