肉苁蓉苯乙醇苷类成分对BSA诱导的肝纤维化大鼠转化生长因子β1表达的影响

The effects of cistanche phenylethanoid glycosides on TGF-β1 expression of rats with hepatic fibrosis induced by BSA

目的:观察肉苁蓉苯乙醇苷类成分(CPhGs)对牛血清白蛋白(BSA)诱导的免疫性肝纤维化大鼠肝组织转化生长因子β1(TGF-β1)表达的影响,探讨其治疗肝纤维化的效果及机制。方法:将75只SD大鼠随机分为6组,即正常对照组,肝纤维化模型组,阳性对照组(复方鳖甲软肝片600 mg/kg),以及CPhGs高(500 mg/kg)、中(250 mg/kg)、低(125 mg/kg)剂量组。CPhGs高、中、低剂量组每组各13只,其余每组各12只。采用皮下及尾静脉注射BSA诱导建立大鼠肝纤维化模型,造模同时灌服相应剂量的受试药物,正常对照组和模型组灌胃给予蒸馏水,其余各组均按设定剂量灌胃给药;给药结束后收集大鼠血清、肝组织,采用全自动生化仪检测大鼠肝功能酶指标,包括血清白蛋白(ALB)、血清总胆红素(TB)、血清直接胆红素(DB)水平;放射免疫法检测血清肝纤维化标志包括血清透明质酸(HA)、层黏连蛋白(LN)、Ⅲ型前胶原(PCⅢ)、Ⅳ型胶原(Ⅳ-C)含量;ELISA测定血清TGF-β1水平;Masson染色观察肝脏病理组织学变化;免疫组化法测定肝组织中TGF-β1的表达。结果:与模型组相比,CPhGs各剂量组肝纤维化大鼠血清中ALB含量增加,中、高剂量组TB、DB含量降低,各剂量组大鼠肝纤维化指标含量均明显降低(P<0.05或P<0.01),血清TGF-β1含量降低(P<0.01),Masson染色结果显示CPhGs各剂量组肝纤维化程度减轻,均显著低于模型组(P<0.01),各剂量组肝组织中TGF-β1蛋白的表达也明显受到抑制(P<0.05或P<0.01)。结论:CPhGs对BSA诱导的免疫性肝纤维化大鼠具有较好的保护作用,对TGF-β1表达的抑制作用可能是其作用机制之一。

OBJECTIVE：To observe the effects of cistanche phenylethanoid glycosides（CPhGs） on TGF-β1expression of rats with hepatic fibrosis induced by bovine serum albumin（BSA）.METHODS：Seventy-five SD rats were randomly divided into six groups：Normal（distilled water-treated）,model（BSA-treated）,positive drug（BSA-treated＋compound Biejia Ruangan tablets（BJRG,600 mg/kg）,and BSA-treated＋CPhGs（125,250,500 mg/kg） groups.BSAtreated＋CPhGs（125,250,500 mg/kg） groups consisted of 13 rats in each group,and other various group had 12 rats in each group.Using intravenously injected BSA-induced rat liver fibrosis model,rats were fed with different therapeutic drugs for 12 weeks.After the experiment serum and liver tissues of rats were collected.Measurements of serum enzymes,liver fibrosis markers,serum TGF-β1 concentration,Masson staining to show the histopathological changes and the expression of TGF-β1 were recorded.RESULTS：Compared with model group,except for ALB and the low dose group TB and DB,various dose CPhGs groups（125,250,and 500 mg/kg） could significantly lower liver enzymes in serum（P〈0.05）,liver fibrosis markers（P〈0.05）,and TGF-β1 content（P〈0.01）.Moreover,Masson staining showed BSA-treated＋CPhGs（125,250,500 mg/kg） groups could alleviate the degree of liver fibrosis,which was significantly lower than the model group（P〈0.01）.The expression of TGF-β1 protein in liver tissue of different dose groups were also inhibited significantly（P〈0.05 or P〈0.01）.CONCLUSION：CPhGs demonstrated protective effects on hepatic fibrosis induced by BSA in rats,and one of mechanisms maybe the inhibited expression of TGF-β1 in hepatic fibrosis tissue.