机构地区:[1]上海中医药大学附属曙光医院,上海中医药大学肝病研究所 [2]上海中医药大学肝肾疾病病证教育部重点实验室 [3]上海高校中医内科学E研究院
出 处:《中西医结合学报》2012年第12期1405-1412,共8页Journal of Chinese Integrative Medicine
基 金:国家自然科学基金资助项目(No.90409020;No.30701070;No.81273729);上海市科学技术委员会启明星计划资助项目(No.08QA14062);上海市重点攻关项目(No.11DZ1971702);王宝恩肝纤维化基金资助项目(No.20100048);上海中医药大学杏林学者项目;上海市教育委员会E-研究院建设计划项目(No.E03008);上海高校创新团队建设项目
摘 要:目的:通过观察经典退黄三方茵陈蒿汤、茵陈五苓散和栀子柏皮汤对二甲基亚硝胺(dimeth-ylnitrosamine,DMN)诱导的大鼠肝纤维化模型的效应,探讨该模型的病机。方法:48只大鼠按体质量分层随机分为正常对照组、模型组、茵陈蒿汤组、茵陈五苓散组和栀子柏皮汤组,采用DMN腹腔注射4周的方法诱导大鼠肝纤维化模型。从造模第3周开始,各药物组在继续造模的同时予以相应的药物干预,正常对照组和模型组给以等量生理盐水。4周末结束实验,杀鼠取材,观察各组大鼠一般情况、肝组织病理学、羟脯氨酸(hydroxyproline,Hyp)含量及肝功能变化。结果:与正常对照组相比,模型组大鼠出现显著的肝损伤和肝纤维化,肝组织Hyp含量显著升高(P<0.01),肝功能显著异常(P<0.01)。与模型组比较,茵陈蒿汤可显著改善肝功能(P<0.05或P<0.01),显著改善肝组织病理改变,降低肝组织Hyp含量及肝脏胶原增生程度(P<0.01);茵陈五苓散可显著降低血清总胆红素含量(P<0.01),对肝组织病理影响不明显;而栀子柏皮汤显著改变肝脏病理,并对肝组织Hyp含量有降低作用。结论:茵陈蒿汤对DMN诱导的大鼠肝纤维化的治疗效果优于茵陈五苓散和栀子柏皮汤;DMN诱导的大鼠肝纤维化模型在其形成期的病机以"湿(瘀)热内蕴"为主,且湿(瘀)热并重,与茵陈蒿汤方证高度相关。OBJECTIVE: To investigate the effects of three classical anti-jaundice formulas Yinchenhao Decoction (YCHD), Yinchen Wuling San (YCWLS) and Zhizi Baipi Decoction (ZZBPD) on liver fibrosis induced by dime- thylnitrosamine (DMN) in rats and explore the formula-syndrome relationship. METHODS: Forty-eight rats were weighted, and divided into five groups: normal control, DMN, YCHD, YCWLS and ZZBPD groups using stratified random method. Liver fibrosis in rats was induced by intraperitoneal injection of DMN for 4 weeks at the dosage of 10 mg/kg body weight, once per day for 3 consecutive days in each week. Each group was gavaged with distilled water (control or model group), YCHD, YCWLS and ZZBPD respectively in the last 2-week modeling period. At the end of the 4:th week, rats were sacrificed and their blood sample and liver tissue were taken for detecting pathology and analyzing of hydroxyproline (Hyp) and liver function. RESULTS: Compared with the normal control group, DMN model group showed liver damage and liver fibrosis, with remarkably increased Hyp content (P〈0.01) and abnormal liver function (P〈0.01). Liver fibrosis induced by DMN in rats was improved by administration of YCHD. Compared with DMN model group, content of Hyp was decreased remarkably (P〈0.01) and liver function and hepatic histology were improved significantly after 2 weeks of YCHD treatment (P〈0.05 or P〈0.01), while these effects were not shown in the YCWLS and ZZBPD groups. Comparison of various parameters between groups showed that content of serum total bilirubin was decreased significantly in the YCWLS group (P〈0.01), and content of hepatic Hyp was decreased in the ZZBPD group. CONCLUSION: Efficacy of YCHD in inhibition of liver fibrosis induced by DMN in rats is far better than YCWLS and ZZBPD. The pathogenesis of the liver fibrosis induced by DMN is mainly damp-heat. In addition, both damp and heat pathogenic factors play very important role in this model. The syndrome is h
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