摘要
AIM:To examine the expressions of matrix metalloproteinases-2(MMP-2)and tissue inhibitor of metalloproteinases-1(TINP-1)in rat fibrotic liver and in normal rat hepatic stellate cells,and to investigate the changes in their expressions in response to treatment with interleukin-10(IL-10)and platelet-derived growth factor(PDGF).METHODS:Rat models of CCl4-induced hepatic fibrosis were established and the liver tissues were sampled from the rats with or without IL-10 treatment,and also from the control rats.The expressions of MMP-2 and TIMP-1 in liver tissues were detected by S-P immunohistochemistry,and their expression intensities were evaluated in different groups.Hepatic stellate cells(HSCs)were isolated from normal rat and cultured in vitro prior to exposure to PDGF treatment or co-treatment with IL-10 and PDGF.MMP-2 and TIMP-1 levels were measured by semi-quantitative reverse transcriptional polymerase chain reaction(RT-PCR).RESULTS:CCl4-induced rat hepatic fibrosis models were successfully established.The positive expressions of MMP-2 and TIMP-1 increased obviously with the development of hepatic fibrosis,especially in untreated model group(84.0%and 92.0%,P<0.01).The positive signals decreased significantly following IL-10 treatment(39.3%and 71.4%,P<0.01 and P<0.05)in a time-dependent manner.TIMP-1 mRNA in PDGF-treated group was significantly increased time-dependently in comparison with that of the control group,but PDGF did not obviously affect MMP-2 expression.No difference was noted in TIMP-1 and MMP-2 expressions in HSCs after IL-10 and PDGF treatment(P>0.05).CONCLUSION:MMP-2 and TIMP-1 expressions increase in liver tissues with the development of fibrosis,which can be inhibited by exogenous IL-10 inhibitor.PDGF induces the up-regulation of TIMP-1 but not MMP-2 in the HSCs.IL-10 inhibits TIMP-1 and MMP-2 expressions in HSCs induced by PDGF.
基金
Supported by the Science and Technology Fund of Fujian Province,No.2003D05
白细胞间介素-10
血小板
生长因子
基因表达
矩阵
金属蛋白酶类-2
组织抑制剂
金属蛋白酶类-1
老鼠
纤维性肝硬化
肝脏疾病
肝脏星形细胞
消化系统
