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为揭示酒精性肝病(ALD)肝纤维化基质降解的病理机制 ,2 8例ALD肝穿刺组织按其纤维化程度分为 3组 ,应用原位杂交技术分别检测各组肝组织内基质金属蛋白酶 1(MMP 1)、基质金属蛋白酶 2 (MMP 2 )、膜型基质金属蛋白酶 1(MT1 MMP)mRNA和基质金属蛋白酶抑制酶 1(TIMP 1)mRNA的表达。结果发现 ,MMP 1、MMP 2、MT1 MMP和TIMP 1mRNA阳性细胞主要位于纤维化的中央静脉、窦周及汇管区等部位周围 ,且MMP 2和MT1 MMPmRNA的表达细胞有重叠 ;MMP 2、MT1 MMP和TIMP 1mRNA表达阳性细胞数随肝纤维化程度的加重而增多 ,而MMP 1mRNA表达阳性细胞数减少 ,且以纤维化中期变化为著 ;MMP 1、MMP 2、MT1 MMP和TIMP 1mRNA表达阳性细胞主要为肝窦壁细胞 ,少数肝细胞亦呈阳性表达。提示MMP 1减少和TIMP 1增多可能是ALD肝纤维化过程中细胞外基质(ECM)沉积、尤其是I型胶原过量沉积的病理机制之一 ;MMP 2和MT1 MMP在基质降解过程中可能有协同作用 ,其表达增多可能对ALD时中央静脉纤维化、肝窦血管化起一定促进作用 ;肝窦壁细胞 (肝星状细胞等 )为肝组织内MMP 1、MMP 2、MT1 MMP和TIMP 1的主要产生细胞
To reveal the pathological mechanism of hepatic fibrosis matrix degradation in alcoholic liver disease (ALD), 28 ALD hepatic puncture tissues were divided into 3 groups according to their degree of fibrosis. The levels of matrix metalloproteinase 1 (MMP 1), matrix metalloproteinase 2 (MMP 2), membrane-derived matrix metalloproteinase 1 (MT1 MMP) mRNA and tissue inhibitor of metalloproteinase 1 (TIMP 1) mRNA expression. The results showed that MMP 1, MMP 2, MT1 MMP and TIMP 1 mRNA positive cells mainly located in the central vein of fibrosis, sinusoid and portal area and other parts of the MMP2 and MT1 MMP mRNA expression of overlapping cells; MMP 2, MT1 MMP And the number of TIMP-1 mRNA positive cells increased with the degree of liver fibrosis, but the number of MMP-1 mRNA positive cells decreased, and the mid-fibrosis was the MMP 1, MMP 2, MT1 MMP and TIMP-1 mRNA positive cells For the hepatic sinusoidal cells, a small number of hepatocytes also showed positive expression. It is suggested that the decrease of MMP-1 and the increase of TIMP-1 may be one of the pathological mechanisms of extracellular matrix (ECM) deposition, especially type I collagen deposition in ALD liver fibrosis. MMP 2 and MT1 MMP may play a synergistic role in matrix degradation Which may play an important role in the central venous fibrosis and hepatic sinusoidal vascularization during ALD. The hepatic sinusoidal parietal cells (hepatic stellate cells, etc.) are the major components of MMP 1, MMP 2, MT1 MMP and TIMP 1 Mainly produce cells