摘要
目的:观察奥曲肽(OCT)对肝星状细胞(HSC)Ⅰ型、Ⅲ型胶原和基质金属蛋白酶2(MMP-2)基因及蛋白表达的影响,阐明其抗肝纤维化的机制。方法:体外培养rHSC-99细胞,以不同浓度OCT作用24h后,MTT法观察细胞增殖,ELISA法测定上清液中Ⅰ型、Ⅲ型胶原,半定量RT-PCR法检测MMP-2、Ⅰ型及Ⅲ型胶原mRNA表达。结果:与对照组比较,OCT能显著抑制体外培养的rHSC-99增殖(P<0.05),在一定剂量范围(1～8μg·L-1)内,随着OCT浓度升高,细胞增殖抑制率增加。与对照组比较,OCT各组细胞上清液中Ⅰ型、Ⅲ型胶原浓度明显降低(P<0.05),且Ⅰ型、Ⅲ型胶原mRNA表达水平显著降低(P<0.05)。与对照组比较,OCT组MMP-2 mRNA呈高表达(P<0.05)。结论:OCT能抑制HSC增殖,下调Ⅰ型和Ⅲ型胶原mRNA及其蛋白表达,上调MMP-2 mRNA表达水平,这可能是其抗肝纤维化作用机制之一。
Objective To investigate the effects of octreotide （OCT） on gene and protein expressions of collagen Ⅰ,collagen Ⅲ and matrix matrixmetlloproteinases 2 （MMP-2）in hepatic stellate cells（HSC） in vitro,and to clarify the mechanism of its anti-hepatic fibrosis.Methods A rat hepatic stellate cell line,rHSC-99,was treated with OCT.Cell proliferation was assessed by MTT colorimetric assay.The contents of collagen Ⅰ,Ⅲ were examined by ELISA;RT-PCR was used to detect mRNA expressions of MMP-2,collagen Ⅰ and collagen Ⅲ.Results Compared with control group,OCT significantly inhibited rHSC-99 proliferation in vitro （P〈0.05）,the inhibitiory rate of cell proliferation was increased with the elevation of the OCT in a certain dose range （1-8 μg·L-1）.Compared with control group,the concentrations of collagen Ⅰ,Ⅲ in OCT groups were reduced significantly,the difference was significant （P〈0.05）;and the mRNA expressions of collagen Ⅰ and Ⅲ were also decreased （P〈0.05）.Compared with control group,MMP-2 mRNA was highly expressed in OCT groups （P〈0.05）.Conclusion OCT could inhibit the proliferation of HSC,down-regulate the expressions of collagen Ⅰ and Ⅲ mRNA and protein,and up-regulate the expression of MMP-2 mRNA.All of these biological effects of OCT on HSC are associated with recovery from liver fibrosis.
出处
《吉林大学学报（医学版）》
CAS
CSCD
北大核心
2009年第6期1052-1056,共5页
Journal of Jilin University：Medicine Edition
基金
福建省科技厅科研基金资助课题(9911)
关键词
奥曲肽
肝纤维化
肝星状细胞
增殖
胶原
基质金属蛋白酶2
octreotide
liver fibrosis
hepatic stellate cells
proliferation
collagen
matrix matrismetlloproteinases 2
