| Objective: There is a dynamic balance between extracellular matrix (ECM)formation and degradation in the fibrous tissue of normal liver. The imbalance between ECM formation and degradation results in hepatic fibrosis. There are more research on the formation and deposition of ECM in the past, while recent years, research on the degradation of ECM are also increasing. However, there have been no tangible progress in the field of clinical treatment of hepatic fibrosis. Developed by pathophysiology depar- tment Ganfukang has been used as the traditional Chinese medicine for treating hepatic fibrosis. Clinical observations in our affiliated hospital have proved its effective. However, further study of its detailed anti-hepatic fibrosis mechanism is still needed. On the basis of the above mentioned theory and research developments, our study was to observe the mechanism of Ganfukang from the perspective of ECM degradation.Method:All SD rats were divided into seven groups: hepatic fibrosis model group(M group),low dose medicine group(LT group),middle dose medicine group(MT group),high dose medicine group(HT group),model control group(MC group),medicine prevention group(P group)and normal control group(C group). Rats were treated subcutaneously with CCl4 to produce the model of hepatic fibrosis. Serum alanine aminotransferase (ALT),aspartate aminotransferase (AST),albumin(A),globulin(G),the ratio of albumin and globulin(A/G) were measured; The liver pathology changes were observed under light microscopy by HE staining; hepatic expression ofα-smooth musle actin(α-SMA) were observed by immunohis- tochemistry; hepatic expression of tissue inhibitor of metalloproteinase -1(TIMP-1) mRNA and Collagen III mRNA were detected by reverse transcription polymerase chain reaction(RT-PCR). At the same period, the rats fed common chow were as normal control.Result: 1.Serum index: Compared to M group, Serum ALT and AST release can be significantly reduced, serum albumin and the ratio of albu- min and globulin can be significantly increased after treating with Ganfu- kang, especially in MT group.2.Pathology of hepatic tissue: The formation of fibrosis, marked fatty degeneration, necrosis, inflammation of hepatocytes, and infiltration of inflammatory cells including macrophages and lymphocytes were seen in the rat livers of M group. Compared to M group, the hepatic necrosis and infiltration of inflammatory cells, particularly in the pericentral region, were significantly diminished in the MT group.3.Immunohistochemistry staining: In the M group, the a-SMA positive cells, representing the transformed HSC, increased in number, size, and immunohistochemical staining intensity compared with those in the other groups.4.Expression of TIMP-1 and Collagen III mRNA: Rats in M group showed higher TIMP-1 levels in liver. The levels decreased in MT group comparison with those in M group, the difference was significant. However, compared with TIMP-1 mRNA in the other groups, there were no significant differences. We found that the pattern of Collagen III mRNA levels was upregulated in M group comparison with those in C group. Compared with Collagen III mRNA expression in M group, the level in MT group decreased significantly.Conclusion: 1.Chinese medicine Ganfukang was a good treatment for liver fibrosis. It significantly reduces the level of TIMP-1 and collagen III mRNA expres- sion in CCl4 -induced rat liver fibrosis.2.The mechanism of Ganfukang's effection on CCl4-induced liver fibrosis, may be related to reduced expression of TIMP-1 levels, thus reducing their inhibition to MMPs.
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