【作者】 黄恩；

【导师】 熊文生；

【作者基本信息】 广州中医药大学 ， 中医内科学（专业学位）， 2013， 硕士

【摘要】 研究背景：肝内胆汁淤积症是由多种原因所导致的肝细胞胆汁分泌或排泄障碍,引起肝内胆汁淤积和血液中胆汁成分增加,但患者胆道并无明显阻塞,可引起不同程度的肝细胞损伤,诱发肝脏的炎症及纤维化。肝内胆汁淤积属于祖国医学中“黄疸”的范畴,临床上常用茵陈蒿汤来治疗,且疗效明显。研究目的：通过动物实验与临床观察,并从病理学和细胞学角度探讨茵陈蒿汤(加味)治疗肝内胆汁淤症的作用机制、临床疗效与安全性。研究方法：实验部分：利用给大鼠灌喂葡萄糖及油脂造成湿热体质,并在人工气候箱中加重湿热体质的形成,建立肝内胆汁淤积湿热证大鼠模型,使用茵陈蒿汤干预治疗,观察相关指标及病理组织的变化,从病理学和分子生物学探讨茵陈蒿汤治疗肝内胆汁淤症的作用机制。1.造模：在长夏季节中将SD大鼠放置于人工气候箱中,并喂食葡萄糖及猪脂,使其形成湿热体质；再采用α-异硫氰酸萘酯(ANIT)造成大鼠肝内胆汁淤积。2.分组：三月龄SD大鼠25只,随机分为3组,第一组对照组7只,第二组造模组和第三组茵陈蒿汤组均为9只。茵陈蒿汤组在造模后第10天使用茵陈蒿汤灌胃,共用药14天。对照组及造模组均使用0.9%生理盐水灌胃。3.检测：利用全自动生化分析仪检测大鼠的TB、DB、ALT、AST、ALP项目。每组大鼠的肝脏组织行病理切片HE染色及免疫组化检查,观察肝脏组织的变化情况。临床部分：根据诊断标准和排除标准在广州中医药大学第一临床医学院脾胃病科病房和门诊中选取50例肝内胆汁淤积症住院患者,采用随机方法将患者分为实验组、对照组,每组25例(每组脱落2例)。治疗组予口服加味茵陈蒿汤,对照组予静脉滴注西药腺苷蛋氨酸粉针剂。观察患者一般情况及临床症状。研究结果：1.茵陈蒿汤能有效地降低造模组大鼠TB、DB、ALT、AST、ALP生化学指标,病理指标显示能较好地降低胆汁淤积所造成的肝脏损害。2.免疫组化观察中,胆汁淤积的大鼠肝脏NTCP表达下降,MRP3的表达则上调,使用了茵陈蒿汤的大鼠肝脏则能分别逆向调整NTCP和MRP3的表达方向。3.临床观察显示加味茵陈蒿汤与西药腺苷蛋氨酸在降低胆红素及肝酶、改善临床疗效方面效果相似,对降低胆红素及改善肝脏酶学方面均有显著疗效,但茵陈蒿汤(加味)对于降低中医证候积分,改善患者临床症状方面优势对照组。结论：菌陈蒿汤是中医治疗黄疸病的代表方剂,能降低试验大鼠和肝内胆汁淤积症住院患者的胆红素、部分肝酶指标及改善患者临床症状,疗效。更多还原

【Abstract】 ObjectiveIntrahepatic cholestasis caused by a variety of reasons hepatocytes or bile excretion disorder, caused by intrahepatic cholestasis and bile composition in the blood increased, but not significantly in patients with biliary obstruction. Intrahepatic cholestasis can cause different degrees of liver cell injury induced liver inflammation and fibrosis. Intrahepatic cholestasis is "jaundice" category in the Chinese medicine, the liver and gallbladder damp-heat syndrome are particularly prevalent, the clinically used yinchenhao decoctionon to treatment, and the effects are obvious.Research purposeWithe animal experiments and clinical observations, and from the pathological and molecular biological study yinchenhao dcoction (modified) treatment of intrahepatic cholestasis of mechanism of action, clinical efficacy and safety.MethodsUsing rats fed with glucose and grease caused by body heat and increase the formation of body heat in the artificial climate chamber, the establishment of damp-heat syndrome rat model of intrahepatic cholestasis, use yinchenhao decoction for comparison, observe the relevant indicators and histopathologicalchanges in molecular gallbladder jaundice provide a theoretical basis. At the same time the clinical use YCHT with western medicine adenosylmethionine comparative observation, to further clarify the yinchenhao decoction efficacy and safety of treatment of intrahepatic cholestasis.Animal experimentModeling:in the long summer festival, SD rats were will be placed in the artificial climate chamber and fed glucose and pig fat, to form the body heat; using rat liver caused by alpha-isothiocyanate naphthyl acetate (ANIT)cholestasis.Grouping:March age25SD rats were randomly divided into three groups, the first group of seven control group, the second group of model group and the third group yinchenhao decoction group are nine.The10th day after,the yinchenhao decoction group and the modeling group will be gavage medication in the14th day. The control group and model group were0.9%saline.Text:automatic biochemical analyzer rats were detected TB, DB, ALT, AST, ALP, GGT and other projects. Liver tissues of rats in each group HE staining and immunohistochemical examination to observe the changes of the liver tissue.Clinical observationSelected50cases of hospitalized patients, according to the diagnostic criteria and exclusion criteriain the Guangzhou University of Traditional Chinese Medicine, First Clinical Medical College stomach Diseases randomized and Outpatient department patients were divided into two groups, the treatment group to oral prescription Yinchenhao decoction, control group received oral medicine adenosinemethionine. Observe the general condition of patients and clinical symptoms.Results1. Yinchenhao decoction can effectively reduce the model group, serum total bilirubin, direct bilirubin, liver enzymes and biochemical indicators in pathological indicators show can reduce liver damage caused by cholestasis.2. In mmunohistochemistry, the decline in cholestatic rat liver NTCP expression, MRP3of expression is raised, use the rat liver YCHT respectively reverse adjustment NTCP and MRP3expression.3. Clinical observation the yinchenhao decoction and western medicine adenosylmethionine in reducing bilirubin and liver enzymes to improve the clinical efficacy similar effect to reduce bilirubin and improve the liver enzymes aspects have a significant effect, but yinchenhao decoction improve the patient to reduce the TCM syndrome score more advantage.ConclusionYinchenhao decoction (modified) on behalf of the prescription of traditional Chinese medicine treatment of jaundice, waiting for reduce bilirubin to improve the enzymology and help patient to prevent cholestasis further development of disease with better clinical efficacy.更多还原