Therapeutic effects and molecular mechanisms of anti-fibrosis herbs and selenium on rats with hepatic fibrosis.

Abstract

To study the therapeutic effects of anti-fibrosis herbs and selenium on hepatic fibrosis induced by carbon tetrachloride (CCl(4)) in rats and the underlining molecular mechanisms. Fifty-three Wistar rats were randomly divided into: normal control group, model control group, colchicine group, anti-fibrosis herbs group (AF group) and anti-fibrosis herbs plus selenium group (AS group). The last four groups were administered with CCl(4) at the beginning of experiment to induce hepatic fibrosis. Then colchicine, anti-fibrosis herbs and selenium were used to treat them. The normal control group and the model control group were given normal saline at the same time. At the end of the 6(th) week, rats in each group were sacrificed. Blood and tissue specimens were taken. Serum indicators (ALT, AST, HA, LN) were determined and histopathological changes were graded. Lymphocyte CD(4) and CD(8) were examined by flow cytometry. Expression of TGF-beta(1) and NF-kappaB was detected by immunohistochemistry and expression of TGF-beta(1) mRNA was detected by semi-quantified RT-PCR. Histological grading showed much a smaller degree of hepatic fibrogenesis in AS group and AF group than that in colchicine group and model control group. The serum content of ALT, AST, HA and LN in AF group and AS group were significantly lower than that in colchicine group (ALT: 65.8+/-26.5, 67.3+/-18.4 and 96.2+/-20.9 in AF, AS and colchicine groups respectively; AST: 150.8+/-34.0, 154.6+/-27.3 and 215.8+/-24.6 respectively; HA: 228+/-83, 216+/-58 and 416+/-135 respectively; LN: 85.9+/-15.0, 80.6+/-18.6 and 106.3+/-14.2 respectively) (P<0.05). The level of CD(4) and CD(4)/CD(8) ratio in AF group and AS group was significantly higher that those in cochicine group (CD(4): 50.8+/-3.8, 52.6+/-3.4 and 40.2+/-2.1 in AF, AS and colchicine groups respectively; CD(4)/CD(8) ratio: 1.45, 1.46 and 1.26, respectively (P<0.05). The expression level of NF-kappaB and TGF-beta(1) in the liver tissues of AF and AS treatment groups was markedly decreased compared with that in cochicine group, and TGF-beta(1) mRNA was also markedly decreased (1.07+/-0.31 and 0.98+/-0.14 vs 2.34+/-0.43, P<0.05). Anti-fibrosis herbs and selenium have beneficial effects on hepatic fibrosis in rats by enhancing immunity and inhibiting NF-kappaB and TGF-beta(1) expressions.