日本血吸虫病肝纤维化小鼠肝脏CTGF、TGFβ_1-mRNA的表达及意义

Expression and significance of connective tissue growth factor and transforming growth factor-beta1 mRNA in murine schistosomiasis liver fibrosis

目的研究结缔组织生长因子(connective tissue growth factor,CTGF)mRNA与转化生长因子-β1(transforminggrowth factor-beta1,TGFβ-1)mRNA在日本血吸虫病肝纤维化小鼠肝脏中的表达及意义。方法用昆明小鼠感染尾蚴复制小鼠日本血吸虫病肝纤维化模型,模型组分别在6、10、14、18周杀鼠,治疗组在6周时予吡喹酮治疗后10、14、18周杀鼠;masson染色并图像分析进行胶原半定量;RT-PCR检测小鼠肝脏CTGFmRNA、TGFβ-1mRNA表达。结果模型组10周时小鼠血吸虫病肝纤维化形成,胶原量进行性增加,肝脏CTGFmRNA表达达高峰,10周、14周、18周时与治疗组相比均有明显的统计学差异(P均<0.01);模型组TGFβ-1mRNA表达水平和CTGFmRNA有相同的变化趋势,但18周时与治疗组已无明显差别(P>0.05);模型组CTGFmRNA和TGF-β1mRNA的表达具有直线相关性。结论CTGF与TGF-β1的基因表达与小鼠日本血吸虫病肝纤维化形成有密切关系;TGF-β1的致纤维化作用可能部分通过CTGF的生物学作用介导;通过阻断CTGF的传导通路可能是肝纤维化治疗的有效靶点。

To study the expression and significance of CTGF mRNA and TGF-β1 mRNA in murine schistosomiasis liver fibrosis, the mice infected with Schistosomas japonicum were randomly divided into the model groups and the therapeutic groups, and subsequently killed at the 6th, 10th, 14th, 18th weeks respectively. The hepatic collagen was semiquantified by computing graphic system after the masson staining and the hepatic expression of connective tissue growth factor（CTGF）, transforming growth factor-βl （TGF-β1） mRNA was detected by reverse transcriptase polymerase chain reaction. Histological changes in HE staining were observed by light microscopy. This model of murine schistosomiasis liver fibrosis had been successfully established at the 10th week and the expression of CTGF and TGF-β1 mRNA in the model groups peaked at the 10th week and then declined. Meanwhile levels of CTGF mRNA remained marked difference compared with those of the therapeutic groups at the 10th, 14th and 18th week. The expression of TGF-β1 mRNA had the same tendency with CTGFmRNA , but it had no marked difference at 18th week compared with that in the therapeutic group. However, the expressions of CTGF and TGF-β1 mRNA in the model groups had positive correlations. It is concluded the expression of CTGF and TGF-β1mRNA is correlated closely to the murine schistosomiasis liver fibrosis; TGF-β1 involved in liver fibrogenesis may transduct the intracellular signalling pathways by CTGF. CTGF may be an effective target to block the development of schistosomiasis liver fibrosis.