Effect of Salidroside on gene expression of CBP and Smad in CCl4-induced liver fibrosis in rats

Abstract

AIM: To study the effect of Salidroside on gene expres- sion of CREB binding protein (CBP), Smad 3 and Smad 7 in rat hepatic fibrosis induced by CCl4. METHODS: Healthy male SD rats were randomly divided into three groups: normal group (n = 10), Salidroside thera- peutic group (n = 40)and fibrosis model group (n = 40). Liver fibrosis was induced by CCl4 subcutaneous injection (300 mL/L, 3 mL/kg, twice per wk for 8 wks). Rats in thera- peutic group received Salidroside (5mg/kg)celiac injection twice a week. The deposition of collagen was examined using Masson staining. The gene expression of Smad 3, Smad 7 and CBP were detected by in situ hybridization and immunohistochemistry. RESULTS: The reduction of collagen deposition and rear- rangement of the parenchyma were observed in the livers of rats in the therapeutic group, in comparison with those in model group (semi-quantitative histological scores: 2.1±0.3 vs 3.6±0.8, P = 0.041;average area of collagen: 138±66 µm 2 vs 691±189 µm 2 , P = 0.046). The positive rate of Smad 3 mRNA expression was significantly lower in therapeutic group than that in model group (0.18±0.03 vs 0.62±0.23, P = 0.026), while the positive rate of Smad 7 protein expression was markedly higher (4.27±0.43% vs 2.86±0.86%, P = 0.035). The OD value of CBP mRNA expression was significantly decreased in therapeutic group, as compared with that in model group (0.092±0.032 vs 0.235±0.025, P = 0.00012). CONCLUSION: Salidroside can effectively reduce CCl4- induced liver fibrosis in rats. The mechanism may be re- lated to its inhibition of Smad 3 and CBP expression, and its promotion of Smad 7 expression.