| Objective: The transition of extracellular matrix (ECM) is regulated by Matrix meta1loproteinases (MMPs) and Tissue inhibitor of metalloproteinases (TIMPs). Thereinto, MMP-1 is important in the degradation of collagen I and III which are the main component of ECM, The activation of MMP-1 is mainly restrained by TIMP-1. This restraint can reduce the degradation of collagen I and III and result in the accumulation of collagen I and III overly in the liver during liver fibrosis. The decrease or disappearance of window of sinusoid-lining endothelium cell(SEC) and formation of basic membrane (BM) are the primarily characteristic of hepatic sinusoid capi1latization which is mainly the result of the aggradations of ECM.The primary components of BM are collagen IV and LM. The aim of this study is to investigate the effects of Kangqian Ruangan Granule on matrix transition and hepatic sinusoid capi1latization in experimental rat liver fibrosis, to discuss its function and mechanism of preventing and curing liver fibrosis. Methods: SD male rats weighted 180±20g were divided into 5 groups randomly, group A: normal control group; group B: CCL4 model group; group C: colchicine group; group D: Kangqian Ruangan Granule low dose group; group E: Kangqian Ruangan Granule high dose group. Group A were given 0. 9% NaCl (10ml/kg) by gastric irrigating (i.g); Group B were subcutaneously injected 250ml/L CCL4 solution 2ml/kg, 2 hypo/week; Group C were given colchicines (i.g) 0. 28mg/kg while subcutaneous ly injecting CCL4; Group D were given Kangqian Ruangan Granule (i.g) 2.5g/kg while subcutaneously injecting CCL.,; Group E were given Kangqian Ruangan Granule (i.g) 5g/kg while subcutaneously injecting CCL4. Every group except group B were at the same disposal 6 hypo/week, 13 weeks continuously. After 13 weeks, put rats to death, and took liver tissue. Histopathologica1 changes were examined by optica1 and electron microscopes; Collagen I III IV and LM in the hepatic tissues were detected by immunohistochemica1 techniques ; MMP-1mRNA and TIMP-1mRNA were examined via in situ hybridization.Results: 1. the results of collagen I III IV and LM by immunohistochemica1 techniques quantity analyses:(1)Group A was lower than the other 4 groups significantly. (2)Group C D E all had differently degree decline comparing with group B, the differences were significant (P<0. 05 ~ P<0. 01), group E was the lowest. (3)There was no difference only in the quantity of Collagen I comparing group Dwith group C (P>0. 05), in other indexes, group D and group E all decreased significantly comparing with group C(P<0. 05 ~ 0. 01). 2. the results of the expression of MMP-lmRNA and TIMP-lmRNA via in situ hybridization by image analyses: Between group B and group A, there had no difference in theexpressions of MMP-1mRNA (P>0. 05); group C D were al1 higher than groupB, but had no difference (P>0. 05); the difference between group E and group B is significant (P<0. 05); Group E is higher than group C significantly (P<0. 05). The expression of TIMP-1mRNA in group B C,D E all increased significantly ,had greatly differences from group A(P<0.01); Group C D E all had differently degree decline comparing with group B, the differences were significant(P<0. 05 ~ P<0. 01), group E is the lowest. Group D and group E all decreased significantly comparing with group C (P<0. 05). 3. Histopathological changes The histopathological degree of liver fibrosis : There were significantly differences between groupC, D E and group B, also between group D E and group C ( P<0.05 ~ P< 0. 01 ). Under electron microscopes, the window of SEC disappeared and full BM formed under endodermis. In group C D E, such changes were lighter group D E are the lightest.Conclusion: Kangqian Ruangan Granule can accelerate the expression of MMP-1, inhibit the expression of TIMP-1mRNA , accelerate the degradation of collagens, inhibit the accumulations of collagen IV and LM effectively, improve the histopathological changes in hepatic tissues and attenuate the degrees of the he... |
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