摘要
目的研究整合素α5β1/FAK信号通路在肝纤维化中的作用以及中药肝复康对此通路的影响。方法将SD大鼠随机分为正常对照组、模型组、肝复康大剂量、中剂量和小剂量治疗组,皮下注射10%CCl4制备肝纤维化模型,自第9周起,给予肝复康灌胃治疗至第20周。采用免疫组化法检测大鼠肝组织整合素α5和整合素β1的表达情况;采用RT-PCR法检测FAK mRNA水平。结果模型组大鼠肝组织整合素α5表达水平(0.50±0.01)比正常对照组(0.23±0.13)明显增高(P<0.01),而肝复康治疗后(大、中、小剂量治疗组分别为0.35±0.03、0.33±0.01、0.38±0.02)比模型组明显降低(P<0.01);模型组大鼠肝组织整合素β1表达水平(0.44±0.02)比正常对照组(0.27±0.01)明显增高(P<0.01),肝复康治疗后(大、中、小剂量治疗组分别为0.37±0.01、0.34±0.01、0.39±0.01)表达水平较模型组明显降低(P<0.01);模型组动物FAK mRNA水平(0.73±0.01)比正常对照组(0.11±0.02)明显增高(P<0.01),而肝复康治疗后(大、中、小剂量治疗组分别为0.33±0.03、0.28±0.01、0.18±0.01)比模型组明显降低(P<0.01)。结论整合素α5β1/FAK信号通路的激活在肝纤维化中发挥重要作用,肝复康治疗肝纤维化作用的机制可能与抑制整合素α5β1/FAK通路的信号转导有关。
Objective To study the effect of traditional Chinese medicine Gan-fu-kang（GFK）on hepatic expression of integrinα5β1/ focal adhesion kinase（FAK） in carbon tetrachloride-induced liver fibrosis in rats.Methods SD rats were randomly divided into control,model,low,middle and high dose of GFK treatment groups.Liver fibrosis models of rats were made by subcutaneously injecting with 10%CCl4.GFK was orally given daily with GFK from week 9 to 20.The expression of integrinα5 and integrinβ1 protein and FAK mRNA were detected by immunohistochemical and RT-PCR techniques,respectively.Results The level of integrinα5 expression in model group（0.50±0.01）was obviously increased as compared with that in control group（0.23±0.13,P0.01）,and it was obviously downregulated in high,middle and low dose of GFK treatment groups respectively（0.35±0.03,0.33±0.01,0.38±0.02）as compared with model group（P0.01）;Similarly,the level of integrinβ1 expression in model group（0.44±0.02） was obviously increased as compared with that in control group（0.27±0.01,P0.01）,and it was decreased in high,middle and low dose of GFK treatment groups respectively（0.37±0.01,0.34±0.01,0.39±0.01） as compared with model group（P0.01）;At the same time,FAK mRNA level in model group（0.73±0.01）was obviously higher than that in control group（0.11±0.02,P0.01）,while it was lower in high,middle and low dose of GFK treatment groups respectively（0.33±0.03,0.28±0.01,0.18±0.01）than that in model group（P0.01）.Conclusion The activated integrinα5β1/FAK signal pathway may play an important role in liver fibrosis,and the therapeutic mechanisms of Gan-fu-kang on hepatic fibrosis may be related to the inhibition of this signal pathway.
出处
《实用肝脏病杂志》
CAS
2012年第2期104-107,共4页
Journal of Practical Hepatology
基金
辽宁省自然科学基金资助(编号:201102055)
