蒿鳖养阴软坚方抗小鼠血吸虫病肝纤维化及其机制的研究  

Therapeutic effect and its mechanism of Haobie Yangyin Ruanjian Prescription on mice with liver fibrosis caused by schistosomiasis

作　　者：寇咏梅[1] 刘洁莹[2] 方步武[2] 

机构地区：[1]天津市第二医院,天津300141 [2]天津医科大学药理教研室,天津300070

出　　处：《现代药物与临床》2013年第3期288-293,共6页Drugs & Clinic

基　　金：天津市应用基础研究计划重点项目(06YFJZJC02900)

摘　　要：目的明确蒿鳖养阴软坚方对血吸虫病肝纤维化的治疗作用,探讨肝星状细胞凋亡与抗血吸虫病肝纤维化的关系。方法血吸虫尾蚴25条/只经腹壁皮肤感染小鼠,12周之后建立小鼠血吸虫病肝纤维化模型。将全部感染小鼠随机分为蒿鳖养阴软坚方(8.20、2.59、0.82g/kg)治疗组、阳性药物(复方鳖甲软肝片组0.54g/kg、秋水仙碱组0.1g/kg)组、模型对照组(短模组、长模组)和正常对照组。蒿鳖养阴软坚方组ig蒿鳖养阴软坚方干粉状提取物混悬液;阳性药物对照组ig相应的阳性药物;模型组ig生理盐水,1次/d,共12周。光镜观察肝细胞病理变化;盐酸水解法测定肝细胞羟脯氨酸含量;免疫组化法测定α-SMA表达和ISOL技术测定细胞凋亡情况。结果蒿鳖养阴软坚方高、中剂量组胶原蛋白含量均明显降低(P<0.05)。模型组HSC细胞α-SMA大量表达;而蒿鳖养阴软坚方组肝星状细胞(HSC)细胞α-SMA表达较模型组明显减少(P<0.01)。蒿鳖养阴软坚方中剂量组比模型组肝星状细胞数量有显著差异(P<0.05),与正常组肝星状细胞凋亡差异无显著性(P>0.05)。结论蒿鳖养阴软坚方对小鼠血吸虫病肝纤维化有治疗作用。抑制HSC的活化,并诱导其发生凋亡,是蒿鳖养阴软坚方抗血吸虫病肝纤维化的机制之一。Objective To explore the therapeutic effect of Haobie Yangyin Ruanjian Prescription on liver fibrosis of schistosomiasis in mice and investigate its mechanism of inducing the apoptosis of hepatic stellate cells（HSC）.Methods Every mouse was infected by 25 schistosoma cercarias through skin of abdominal wall,and liver fibrosis was induced after 12 weeks.The infected mice were randomly divided into eight groups：high-,mid-,low-dose（8.20,2.59,and 0.82 g/kg）Haobie Yangyin Ruanjian Prescription groups,positive control group（Componud Biejia Ruangan Tablet 0.54 g/kg group and colchicine 0.1 g/kg group）,model control group（3 months after infection group,6 months after infection group）,and normal control group.Haobie Yangyin Ruanjian Prescription groups and the positive control groups were orally given Haobie Yangyin Ruanjian Prescription and positive control drug powder extractive suspension once daily,respectively.Ig administration of physiological saline to mice in model group once daily lasted for 12 weeks.Hepatic tissue was obtained at the end of the experiment to observe the pathological change under microscope,to determine the content of hydroxyproline（Hyp）,and to set out α-SMA expression and cell apoptosis using immunohistochemical method.Results Compared with the model group,collagen content of high-and mid-dose Haobie Yangyin Ruanjian Prescription groups was significantly lower（P＆lt;0.05）.α-SMA of HSC expressed a lot in the model group,which demonstrated schistosomiasis induced the activation of HSC.α-SMA expression of HSC in the treatment groups was evidently reduced（P＆lt;0.01）,reminding HSC activation was inhibited.The quantity of HSC in mid-dose HYRP group was significantly different to that in the model group（P＆lt;0.05）,but had no remarkable difference compared with the normal control group（P＆gt;0.05）.Conclusion Haobie Yangyin Ruanjian Prescription has the therapeutic effect on the liver fibrosis of schistosomiasis in mice.It could significantly alleviate the de

关 键 词：蒿鳖养阴软坚方 血吸虫病肝纤维化 羟脯氨酸 Α-平滑肌肌动蛋白 肝星状细胞凋亡 

分 类 号：R285.5[医药卫生—中药学]