Alleviation of CCl4-induced cirrhosis in rats by tetramethylpyrazine is associated with downregulation of leptin and TGF-beta1 pathway.

This study was conducted to investigate the effect of tetramethylpyrazine (TMP) on CCl(4)-induced fibrosis in rats and the possible roles of leptin, TGF-beta1, Smad3, and Smad7 in this process. Liver fibrosis in rats was induced by the subcutaneous injection of 60% CCl(4) (0.3 mL /100 g body weight, biweekly ) for 12 weeks. Rats in TMP prevention and treatment groups were given TMP (10 mg /100 g body weight, daily) by gavage from days 1 and 31 after the start of CCl(4) injection, respectively. The mRNA expression of leptin, OB-Rb, TGF-beta1, and TGF-beta RII in the liver were detected by RT-PCR, whereas Smad3 and Smad7 protein were determined by Western blot. The results showed that hepatic cirrhosis was obviously alleviated in both TMP prevention and treatment groups. The mRNA expression of leptin, OB-Rb, TGF-beta1 and -beta RII, and Smad3 protein were higher in the cirrhotic models. In TMP prevention and treatment groups, these markers of expression were higher, compared with that of the normal control, but were lower when compared with that of the cirrhotic model group. Smad7 protein expression was lower in the cirrhotic model group than in the normal control. Smad7 expression in TMP prevention and treatment groups was higher, compared with that in the cirrhotic model group. Liver collagen in the TMP prevention group was the lowest among all CCl(4) injection groups. In conclusion, TMP can prevent and alleviate the development of liver fibrosis in rats. The possible mechanism could involve the downregulation of leptin, Ob-Rb, TGF-beta1, TGF-beta RII, and Samd3, and upregulation of Smad7.