Effects of ligustrazine on transforming growth factor beta-β_1/Smads signal pathway of liver fibrosis in rats

Objective To investigate the therapeutic effects of ligustrazine on experimental hepatic fibrosis in rats,and to appraise the effects on TGF-β_1/Smads signal pathway.Methods Hepatic fibrosis was induced by subcutaneous injection of carbon tetrachloride in 70 male SD rats(twice a week,3 mL/kg)within 8 weeks and another 10 rats were routinely fed as normal group(N group).16 rats were sacrificed to ensure the presence of hepatic fibrosis(M group),then the rest rats with hepatic fibrosis were randomly derided into two groups receiving intraperitoneal injection of ligustrazine(80 mg·kg~(-1)·d~(-1),T group)and the same dosage of normal saline(R group)for 8 weeks.The staging of hepatic fibrosis was assessed through HE staining and observed under light microscope(semi-quantitative scaling system,SSS).The area density of collagen in liver speciments was assessed through Masson staining;and the expression of TGF-β_1,Smad3 and Smad7 in hepatic tissue were assessed by fluorescence quantitative polymerase chain reaction(PCR).Results①The staging of hepatic fibrosis in T group was obviously reduced when compared with R group(7.8±2.5vs 10.2±2.8;P0.05);the area density of collagen in liver tissues was obviously lower in T group(11.68±2.26vs 18.84±2.74,P0.01).②The expression of TGF-β_1 and Smad3 were markly elevated in M group than those in N group(1.54±0.08 vs 0.78±0.15,1.62±0.03vs 0.88±0.17,respectively;P0.01),the expression of Smad7 in M group was reduced (0.88±0.11vs 1.31±0.02,P0.01).③Compared to M group,the expression of TGFβ1 and Smad3 in T group was markly decreased(1.02±0.09vs 1.54±0.08,1.07±0.01vs 1.62±0.03,respectively;P0.01), whereas the Smad7 was increased(1.15±0.01vs 0.88±0.11;P0.01).Conclusion Ligustrazine has obvious therapeutic effect on hepatic fibrosis in rats.The mechanism may be correlated with reduced expression of TGFβ1 and improvement of the disequilibrium of Smads3 and Smads7.(Shanghai Med J,2007,30:530-533)