Effect of N-Acetylcysteine Activated Carbon Sustained-release Microcapsules on the Expression of Intracellular Fibroblast Signaling Molecules in Rat Liver Fibrosis

OBJECTIVE To study the effects of N-acetylcysteine activated carbon sustained-release microcapsule (ACNAC) by oral administration on hepatic fibroblast signaling molecule expression in rats with hepatic fibrosis. METHODS ACNAC was prepared by gelatin entrapping with acetylcysteine-loaded activated carbon. The rat model of liver fibrosis was prepared with carbon tetrachloride (CCl₄). The rats were given ACNAC high, middle and low dose of 80 mg·kg^-1·d^-1, 40 mg·kg^-1·d^-1, 20 mg·kg^-1·d^-1 (calculated according to acetylcysteine), NAC and silybin as the positive control drug by gavage administration. Rats were sacrificed after 8 weeks of treatment. The effects of ACNAC on the expression of intracellular signal molecules were evaluated by rat liver function, pathological sections and immunohistochemistry. RESULTS CCl₄-induced rat liver fibrosis model was successfully established. The pathological changes of liver tissue were observed by HE staining and reticular fiber staining. The degree of hepatic fibrosis was grade Ⅲ-Ⅳ, and immunohistochemistry showed that TGF-β₁/Tβ -R1 and Samd2/3 were abundantly expressed. ACNAC, NAC and SM had significant therapeutic effects on serum ALT, AST and Tbil in rats with hepatic fibrosis. The ACNAC high dose group was superior to NAC and SM (P<0.05). The pathological sections of liver tissue with treatment groups showed improvement of hepatic fibrosis. Immunohistochemistry showed that TGF-β1/Tβ-R1 and Samd2/3 expression were decreased in the NCSM group, and the NCSM high dose group (80 mg·kg^-1·d^-1) expression was significantly different (P<0.05). CONCLUSION ACNAC could significantly inhibit the expression of TGF-β₁/Tβ-R₁ and Smad2/3 in rat liver fibrosis. The effect of ACNAC on liver fibrosis was significantly improved, and has a better therapeutic effect than of NAC and the control drug silybin.