红景天甙对肝纤维化大鼠肝组织CBP、Smad基因表达的影响

Effect of Salidroside on gene expression of CBP and Smad in CCI_4-induced liver fibrosis in rats

目的:研究红景天甙对CCl4诱导的肝纤维化大鼠肝组织CBP、Smad基因表达的影响. 方法:SD大鼠90只分为3组:正常对照组(C组)、模型组(M组)和红景天甙干预组(T组).以CCl4SC诱导肝纤维化,T组在造模同时给予红景天甙溶液ip.HE和Masson染色观察肝脏胶原沉积情况,原位杂交和免疫组化检测肝组织Smad 3,Smad 7和CBP基因表达. 结果:T组肝脏组织学积分减少(2.1±0.3 vs 3.6±0.8, P=0.041),胶原平均面积显著减少(1 38±66 vs 691±189 μm2,P=0.046);肝脏Smad 7蛋白表达阳性率增加[(4.27±0.43)%vs(2.86±0.86)%,P=0.035, P<0.05];Smad 3mRNA表达阳性率减少(0.18±0.03 vs 0.62±0.23,P=0.026),CBP mRNA表达吸光度值亦明显减少(0.092±0.032 vs 0.235±0.025,P=0.00012). 结论:红景天甙能有效抑制Smad 3和CBP基因表达, 促进Smad 7表达,从而干扰肝纤维化的形成.

AIM: To study the effect of Salidroside on gene expression 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 therapeutic 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 therapeutic 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 rearrangement 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±66μm2 vs 691±189μm2, 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 CCI4-induced liver fibrosis in rats. The mechanism may be related to its inhibition of Smad 3 and CBP expression, and its promotion of Smad 7 expression.