Experimental Studies Of FFHQKL On Anti-hepatic Fibrosis In Rats

Excessive aggradation of extracellular matrix(ECM) in the liver is the pathologic characteristic of hepatic fibrosis.The development of liver fibrosis is a dynamical process which is mainly due to the activation of the hepatic stellate cells(HSC), including not only excessive synthesis of ECM, but also its deficient degradation.So,it is important for reversing hepatic fibrosis to inhibit the activation of HSC,decrease the production of ECM and accelerate the degradation of ECM. ECM degradation was mainly regulated by matrix metalloproteinases (MMPs) and its inhibitors (Tissue inhibitor of metalloproteinases, TIMPs).MMPs degrade ECM and reverse fibrosis,TIMPs restrain MMPs' enzyme activity and accelerate the development of fibrosis.Many studies proved that liver fibrosis can be reversed. In the recent years, the experimental and clinical studies on anti-hepatic fibrosis of Chinese traditional medicine have achieved remarkable development. Fufanghuangqikeli(FFHQKL) is consisted of ten kinds of Chinese herbal compound which could effectively inhibit the copy of virus B and improve the function of liver. But, by now, it was not reported in china and abroad if FFHQKL could reverse hepatic fibrosis. In order to evaluate the curative effect and explore the possible mechanism of FFHQKL on anti-hepatic fibrosis, one hundred and eight male SD rats were randomly divided into five groups: FFHQKL high dosage therapeutic group, FFHQKL low dosage therapeutic group, fufangbiejiaruanganpian(FFBJRGP) therapeutic group,model group and normal control group.The rats, except normal contral group, was given intraperitoneal injection of porcine serum twice a week to establish the model of experimental immuno-damaged hepatic fibrosis. After successfully established the liver fibrosis model, FFHQKL was given in high and low dosage to treat the rats with liver fibrosis.By using HE staining and special staining, the dynamical changes ofhepatic histology of rats were observed to determine the curative effect of FFHQKL. By using immunohistochemical method, the dynamic changes in expression of MMP-13, MMP-2, TIMP-l,TIMP-2 and a-SMA were determined in liver tissues from the experimental rats.We found that typical liver fibrosis of rats was developed after ten weeks of intraperitoneal injection of porcine serum. The degree of liver fibrosis was continuously increased in the model group rats. The degree of liver fibrosis was increased in the FH,FL and R group rats one month after the treatment,and evidently decreased in those group rats 2,3 months after the treatment. With the increased degree of liver fibrosis, the expression ofa-SMA,TIMP-l and TIMP-2 in the model group rats was continuously increased and the expression of MMP-13 and MMP-2 was decreased continuously. In comparison with model group, the expression ofa-SMA,TIMP-l and TIMP-2 was significantly decreased and the expression of MMP-13 and MMP-2 was significantly increased 2, 3 months after the treatment in the FH,FL and R group rats, but no significant difference among FH,FL and R group. The study proved that FFHQKL could inhibit the activation of HSC, increase the expression of MMP-13,MMP-2, down-regulate the expression of TIMP-land TIMP-2, accelerate the degradation of ECM and reverse liver fibrosis,...