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首页> 外文期刊>World Journal of Gastroenterology >Effect of interleukin-10 and platelet-derived growth factor on expressions of matrix metalloproteinases-2 and tissue inhibitor of metalloproteinases-1 in rat fibrotic liver and cultured hepatic stellate cells
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Effect of interleukin-10 and platelet-derived growth factor on expressions of matrix metalloproteinases-2 and tissue inhibitor of metalloproteinases-1 in rat fibrotic liver and cultured hepatic stellate cells

机译：白细胞介素10和血小板衍生生长因子对大鼠纤维化肝和肝星状细胞中基质金属蛋白酶2表达和金属蛋白酶1组织抑制剂的影响

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AIM: To examine the expressions of matrix metalloproteinases-2 (MMP-2) and tissue inhibitor of metalloproteinases-1 (TIMP-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 CCl_4-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: CCl_4- 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.
机译：目的：探讨基质金属蛋白酶-2（MMP-2）和组织蛋白酶-1（TIMP-1）在大鼠纤维化肝和正常大鼠肝星状细胞中的表达，并探讨其在反应中的表达变化用白介素10（IL-10）和血小板源性生长因子（PDGF）治疗。方法：建立由CCl_4诱导的肝纤维化的大鼠模型，并从接受或未接受IL-10治疗的大鼠以及对照大鼠中取样肝组织。用S-P免疫组织化学法检测肝组织中MMP-2和TIMP-1的表达，并评价不同组的表达强度。从正常大鼠中分离出肝星状细胞（HSC），并在暴露于PDGF处理或与IL-10和PDGF共同处理之前进行体外培养。通过半定量逆转录聚合酶链反应（RT-PCR）测量MMP-2和TIMP-1的水平。结果：成功建立了CCl_4诱导的大鼠肝纤维化模型。随着肝纤维化的发展，MMP-2和TIMP-1的阳性表达明显增加，尤其是未经治疗的模型组（84.0％和92.0％，P <0.01）。 IL-10治疗后，阳性信号以时间依赖性方式显着下降（39.3％和71.4％，P <0.01和P <0.05）。与对照组相比，PDGF治疗组的TIMP-1 mRNA呈时间依赖性显着增加，但PDGF对MMP-2表达无明显影响。 IL-10和PDGF处理后，HSC中TIMP-1和MMP-2的表达没有差异（P> 0.05）。结论：随着纤维化的发展，肝组织中MMP-2和TIMP-1的表达增加，外源性IL-10抑制剂可抑制其表达。 PDGF诱导HSC中TIMP-1上调，但不诱导MMP-2上调。 IL-10抑制PDGF诱导的HSC中TIMP-1和MMP-2的表达。

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