Effects And Mechanisms Of Shaoqiduogan On Immunological Liver Injury And Hepatic Fibrosis

Objective To investigate the effects of SQDG on Bacillus Calmette Guerin (BCG) plus lipopolysaccharide(LPS)-induced immunological liver injury in mice as well as its possible mechanisms, to study the therapeutic effects and mechanisms of SQDG on immunological hepatic fibrosis induced by human albumin in rats . At the same time the pharmacodynamics of SQDG was compared with total glucosides of paeony (TGP) or astragalosid.es (ASTs) of effective dose.Methods The model of immunological liver injury in mice and immunological hepatic fibrosis induced by human albumin were prepared. The levels of alanine aminotransferase(ALT), aspartate aminotransferase(AST) , nitric oxide(NO) in serum, malondiadehyde(MDA) content, superoxide dismutase(SOD) and glutathione peroxidase(GSH-Px) activities in liver homogenate were assayed by spectrophotometry; tumour necrosis factor- α (TNF- α ) activity was determined by ridioimmunoassay; serum hyaluronic acid ( HA) and procollagen III (PC III) were determined by ridioimmunoassay. Liver collagen level was determined by measuring hydroxyproline(Hyp) content in fresh liver samples. The level of interleukin-1 (IL-1)was assayed by MTT dye reduction. Hepatic tissue sections were stained with hematoxylin and eosin and examined under a light microscope.Results (1) SQDG (60,120,240mg?kg"') was able to significantly decrease liver index, spleen index, and decrease serum transaminase (ALT, AST) levels of immunological liver injury's mice induced by BCG plus LPS, attenuate the area and extent of necrosis and reduce the infiltration of inflammatory cells. Furthermore, SQDG also decreased MDA content and improved the reduced SOD and GSH-Px levels in liver homogenate. Meanwhile, SQDG significantly lowered increased NO level in serum and inhibited the production of TNF-a and IL-1 by peritoneal macrophages. SQDG at the concentrations of 20~80mg ? L"1 were able to inhibit the levels of TNF- a and IL-1 directly produced by KC that induced with LPS. (2) Histological results showed that SQDGC 85 n 170mg ?kg"1) improved the human albumin-induced alterations in the liver structure, alleviated lobular necrosis and significantly lowered collagen content. The anti-fibrotic effects of SQDG also confirmed by decreased serum content of HA and PC III in SQDG-treated group. Moreover, the treatment with SQDG effectively reduced the hydroxyproline content in liver homogenate. However, the levels of ALT and AST increased in fibrotic rats but had no significance compared with normal control, whereas the ratio of A/G decreased also had no significance. SQDG had no effect on level of ALT ,AST and the ratio of A/G. Furthermore, SQDG treatment significantly blocked the increase in MDA, associated with a partially elevation in liver total antioxidant capacity including SOD and GSH-Px. (3) Comparing with TGP and ASTs. SQDG significantly further changed the serum transaminase levels, MDA production while had no difference effects on other indices.Conclusion SQDG possesses protective action on immunological liver injury in mice, which was related to direct with free radical scavenging, increasing the content of SOD and GSH-Px, immunoloregulation and so on. Meanwhile, SQDG have beneficial effects on hepatic fibrosis in rats by inhibition of collagen synthesis, decreasing oxidative...