Curative Effect Of AKF-PD On Rat Liver Fibrosis Induced By CCl₄

Objective To observe the treatment of different doses AKF-PD on CCl4-induced rat liver fibrosis, and to explore the main mechanism of AKF-PD on rat liver fibrosis.Methods 120 Wistar rats were randomly divided into normal group (n=15),model group (n=15),AKF-PD treatment groups (n=15×4), PFD treatment group, IFN-a treatment group.The rats of model group, AKF-PD treatment groups, PFD treatment group and IFN-a treatment group accepted intraperitoneal injection of CC14(CC14 and olive oil 1:1, 2ml/kg/week, twice a week)for 8 weeks.The rats of normal group were given intraperitoneal injection of olive oil(dose, method with the model group).In the 9th week, normal group and model group were given CMC-Na 6ml/Kg administered once a day; four treatment groups of AKF-PD (30mg/kg group,60mg/kg group,120mg/kg group,240mg/kg group) and PFD treatment group were given corresponding doses of AKF-PD, PFD gavage once a day; IFN-a treatment group received subcutaneous injection of IFN-a at 10,0000 units per rat every day. At the end of 11 weekend, all rats were killed with anesthesia, and the liver tissues were given HE,Masson staining, than observe the liver infla-mmation semi-quantitative score, hepatic fibrosis semi-quantitative score of liver tissues, detect liver tissueⅠ,Ⅲcollagen area percentage by measurement of immunohistochemical staining and detect the expression of liver collagenⅠ,collagenⅢ,TGF-β, a-SMA, CTGF, MMP-9 and TIMP-1mRNA with Real time-PCR.Results In the end of the experiment, compared with the normal group, liver inflammation, hepatic fibrosis semi-quantitative score,Ⅰ,Ⅲcollagen protein and mRNA expression was significantly higher (P<0.05). Compared with model group, liver inflammation andⅠ,Ⅲcollagen protein of AKF-PD treatment groups decreased significantly(P<0.05); hepatic fibrosis semi-quantitative score,Ⅰ,Ⅲcollagen mRNA of AKF-PD60mg,120mg,240mg treatment group was significantly de-creased (P<0.05).Compared with model group, the a-SMA expression of AKF-PD(60,120,240mg)treatment groups was significantly decreased(P <0.05);CTGF, TGF-β1 and TIMP-1 mRNA expression of AKF-PD treat-ment groups was significantly decreased (P<0.05),while MMP-9 mRNA expression of witch was no significant difference(P> 0.05).The hepatic fibrosis semi-quantitative score, andⅠ,Ⅲcollagen protein and mRNA of AKF-PD240mg treatment group no higher than PFD240mg treatment group.The hepaticⅠ,Ⅲcollagen protein of AKF-PD240mg treatment group lower than IFN-a treatment group.Conclusion AKF-PD can improve rat liver fibrosis induced by CCl4 with AKF-PD for 3weeks, and its effects are dose dependent, and 240mg/Kg.d is the best therapeutic dose.The effect of AKF-PD240 mg/Kg.d on liver fibrosis is equal to the same dose of PFD and better than IFN-a. The mechanism of AKF-PD on liver fibrosis may be as follows:inhibition of inflammation of the liver, inhibition of hepatic stellate cell activation,down to promote fibrosis factor TGF-β1 and CTGF mRNA expression, than inhibit the synthesis of ECM, inhibiting the expression of TIMP-1,regulate the degradation of ECM.