| Fibrosis is a crucial stage, as well as an important pathological characteristic during progression from chronic liver injury to cirrhosis. It occurs when the synthesis of extracellular matrix (ECM) exceeds the degradation, or matrix remodels; especially when interstitial collagen (Type I and III collagen) deposits excessively. Matrix metalloproteinases (MMPs) comprise a family of zinc-dependent enzymes that specifically degrade ECM components, and their specific inhibitors - tissue inhibitors of metalloproteinses (TEMPs) may suppress their activities. MMP-1 may be responsible for degrading type I and III collagen during chronic liver injury. Excessive depositions of type I and III collagen occur as a consequence of diminished breakdown which follows the disproportion of MMP-1 and TEMP-1.Chinese medicine is regarded as one of effective methods for anti-fibrosis. Chinese Herbal of 'Benefit Gas and Soften Liver' (PGSL) has been applying as an experiential pharmaceutical preparation in Dalian Chinese Medicine Hospital. More than 3000 cases of patients with chronic liver diseases were administered PGSL during recent 40 years, and preventive effects on fibrosis and cirrhosis were found in the course of following up. Infection of hepatitis B virus is the main cause of chronic liver diseases in China. At present, animal model of fibrosis remains unable to be produced using hepatitis B virus. Previous study revealed that immune fibrosis model made with human serum albumin (HSA) in rat was similar to hepatitis B virus-induced fibrcsis morphologically and patncgcnically.Based on the previous work above, in this paper, we built immune fibrosis model with HSA in rat and monitored the protein expression and gene expression of MMP-1/TIMP-1 simultaneously during fibrosis process, which was aimed at evaluating the roles of MMP-1/TIMP-1 in the course of formation and progression of fibrosis. We also investigated protective effect of PGSL on hepatic fibrosis and its mechanism,especially whether some changes of MMP-1 and TIMP-1 are related to the protective effect.Dynamic Observation of MMP-l/TIMP-1 Expression during Process of Experimental Immune Hepatic FibrosisThe establishment of fibrotic animal model was improved somewhat according to the method of Blackwell, which was to attack rats with HSA intravenously through coccygeal veins after making rats sensitized by HSA. Liver tissues were obtained after 0, 2, 4, 6, and 8 weeks. Liver Hydroxyproline(HYP) contents and hematoxylin and eosin (HE) staining were studied to monitor the process of fibroproliferation. The protein expression and the gene expression of MMP-1/TIMP-1 were analyzed using ELISA and semi-quantitative RT-PCR, respectively. Results were as followed: Gradual formation of hepatic fibrosis was detectable, which indicated an ideal model to observe the process of generation and development of fibrosis. Protein expression of MMP-1 was present in normal liver, developing fibrosis and cirrhosis, and remained more or less unchanged (p>0 05), while that of TIMP-1 enhanced progressively (the values after 4 weeks compared with that in 0 week showed statistical difference, p<0.01) and reaches a peak in the stage of cirrhosis (the increasing value approached 4 folds of that in 0 week). None of MMP-1 mRNA expression differed significantly during fibrosis process (p>0.05), however, accompanied by an alteration of TIMP-1mRNA expression on the increase with the time going (those after 4 weeks compared with that in 0 week, p<0.01). MMP-l/TIMP-1 ratio tended towards a decrease in this process, especially after 4 weeks-displaying a profound change (p<0.01). Moreover, there was an increasing tendency in the level of TIMP-1 and a decreasing tendency in the MMP-l/TIMP-1 ratio with the increasing extent of fibrosis when we redivided the rat groups based on the fibroproliferative grade ( ' -' ~ ' + + + ' ).Protection and Treatment Effects of PGSL on Immune Hepatic Fibrosis in RatPGSL is composed of astragalus root(50g), ovate atractylodes(20g), salvia root(25g),...
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