Molecular Mechanism Research Of Sulfotanshinone Sodium Injection On Hepatic Fibrosis

BackgroundHepatic fibrosis is a pathological changes. It is sustained by the liver damage, theexcessive accumulation of extracellular matrix and the imbalance degradation.Viruses, ethanol, autoimmune disease and others can cause hepatic fibrosis, graduallyturned into liver cirrhosis and liver cancer. It is very important for prevention andtreatment of liver cirrhosis by blocking the occurrence and development of liverfibrosis. Tanshinone ⅡAis a kind of diterpene quinone compounds isolated fromDanshen.It passes through sulfonation become Tanshinon ⅡAsilate which has manypharmacological effects. This research focuses on investigate the protective effects ofSodium Tanshinon ⅡAsilate on CCl4-induced hepatic fibrosis in rats.Methods48SD rats were randomly divided into control group (N group), model group (Mgroup), high-dose group (H group), low-dose group (L group). Apart from the Ngroup, the rats in other three groups administered50%CCl4(1mL·kg-1) for inductionof hepatic fibrosis. The rats in the H group (15mL·kg-1) were intraperitoneal injectedadditionally with Sulfotanshinone Sodium Injection once every day. The rats in the Lgroup (5mL·kg-1) were intraperitoneal injected additionally with SulfotanshinoneSodium Injection once every day. After6weeks, macroscopic features of the liver andweight ratio of liver to body were measured. Liver fibrosis of the rats was evaluatedby HE and Masson’s trichrome staining. Activities of serum TBIL, ALT and ASTwere checked with automated biochemistry analyzer. Serum levels of hyaluronic acid(HA), Laminin (LN), type Ⅳ collagen (CⅣ) and type Ⅲ procollagen peptide (PC-Ⅲ) were detected by radioimmunoassay (RIA). The expression of NF-кB and IкBα wasdetected by western blot.Results1. Compared with N group, the body weight at the end of6weeks was significantlydecreased in M group, L group and H group（P＜0.05）. H group significantlyincreased the body weight compared with M group and L group (P＜0.05).2. Compared with N group, the liver weight was significantly increased in M group,L group and H group（P＜0.05）. H group significantly decreased the liver weightcompared with M group (P＜0.05).3. Compared with N group, the liver index was significantly increased in M group,L group and H group（P＜0.05）. H group significantly decreased the liver indexcompared with M group (P＜0.05).4. Compared with N group, the serum concentrations of TBIL was significantlyincreased in M group, L group and H group（P＜0.05）. H group significantlydecreased the serum concentrations of TBIL compared with M group and L group(P＜0.05).5. Compared with N group, the serum concentrations of ALT was significantlyincreased in M group, L group and H group（P＜0.05）. H group significantlydecreased the serum concentrations of ALT compared with M group and L group(P＜0.05).6. Compared with N group, the serum concentrations of AST was significantlyincreased in M group, L group and H group（P＜0.05）. H group significantlydecreased the serum concentrations of AST compared with M group and L group(P＜0.05).7. Compared with N group, the serum concentrations of HA was significantlyincreased in M group, L group and H group（P＜0.05）. H group significantlydecreased the serum concentrations of HA compared with M group and L group(P＜0.05).8. Compared with N group, the serum concentrations of LN was significantly increased in M group, L group and H group（P＜0.05）. H group significantlydecreased the serum concentrations of LN compared with M group and L group(P＜0.05).9. Compared with N group, the serum concentrations of CⅣ was significantlyincreased in M group, L group and H group（P＜0.05）. H group significantlydecreased the serum concentrations of CⅣ compared with M group (P＜0.05).10. Compared with N group, the serum concentrations of PC-Ⅲ was significantlyincreased in M group, L group and H group（P＜0.05）. H group significantlydecreased the serum concentrations of PC-Ⅲ compared with M group and Lgroup (P＜0.05).11. The liver fibrosis were classified according to Plan for pevention and treatment ofviral hepatitis. The results showed that structure in N group is normal, comparedwith M group, the fibrosis degree of H group have significantly improved (P <0.05).12. Western blotting demonstrated that L and H groups decreased the level of nuclearNF-кB compared with M group (P＜0.05). Compared with M group, L and Hgroups dose-dependently increased the level of cytosolic NF-кB and IкBα (P＜0.05).ConclusionsThe experimental results showed that Sulfotanshinone Sodium Injection canprevent the progression of liver angiogenesis and alleviate on CCl4-induced hepaticfibrosis possibly by regulating the expression of NF-кB and IкBα.