【作者】 史亚祥；

【导师】 薛博瑜；

【作者基本信息】 南京中医药大学 ， 中医内科学， 2009， 博士

【摘要】 酒精性脂肪肝(AFL)是指因摄入酒精所引起的肝细胞内脂质蓄积超过肝湿重5%的肝损害性疾病,是临床最常见、最早期的酒精性肝病(ALD)之一。在我国,酒精引起的肝脏疾患已成为仅次于病毒性肝炎的第二大病因,而且随着人民生活水平的日益提高,饮酒人数的逐年增加,酒精性肝病有迅速增加趋势,已成为危害国民健康的又一严重疾病。现代医学治疗除了戒酒、对症治疗外,尚无特效的疗法。针对这种现状,我们在导师指导下,从四个方面较为详细而系统地研究和阐述了酒精性脂肪肝的理论、临床以及实验的问题。第一部分为中医理论探讨。一是提出了酒精性脂肪肝的发生与身体禀赋,脾胃虚弱、饮酒过量、饮食不节等因素有关。其中素体不足、饮食不节等影响本病的发生、转归与预后,而饮酒过量是本病发生的直接原因。二是提出脾虚失运为本病发病的内在基础,痰瘀互结为本病发生的病理关键,认为饮食不节或饮酒过度,脾失健运,肝失疏泄,湿热蕴结脾胃,痰浊内生,气滞血瘀,最终导致气滞、痰湿、瘀血互结,积于胁下,病位在肝脾,与肾有关。其病机可概括为肝失疏泄,肝血瘀滞;脾失健运,湿邪不化,痰浊内生:肾气失化,痰瘀留滞等。三是提出了扶脾活血化浊为治疗大法,本病为本虚标实之证,应标本同治,治标之旨,应化浊祛瘀;治本之要,当扶脾益肾。第二部分为临床研究。目的:观察消脂活血饮联合西利宾胺治疗酒精性脂肪肝(AFL)的临床效果。方法:将89例酒精性脂肪肝患者随机分成三组,其中中西药结合治疗组29例、中药组30例、西药组30例,三组病人在戒酒的基础上,辅以多种维生素口服,中西药结合组给予复方中药消脂活血饮和西利宾胺,中药组服用复方中药消脂活血饮;西药治疗组给予西利宾胺治疗,评价三组的疗效。结果:中西药结合组29例临床治愈12例,有效15例,无效2例,总有效率93.1%。中药组30例中临床治愈6例,有效12例,无效12例,总有效率60.0%。西药组30例中临床治愈6例,有效11例,无效13例,总有效率56.7%。三组有效率比较差异有显著性意义,P＜0.05。结论:消脂活血饮联合西利宾胺治疗酒精性脂肪肝,综合疗效优于单用西药和中药,具有明显改善临床症状和降低血脂的效果。第三部分为实验研究。目的:探讨消脂活血饮联合西利宾胺治疗酒精性脂肪肝的机理。方法:建立酒精性脂肪肝大鼠模型,随机分为正常对照组、实验模型组、中药治疗组、西药治疗组和中西药结合组,分别给药后观察药物对模型大鼠血脂、肝体比、肝脏病理改变、胰岛素抵抗及瘦素的影响。结果:消脂活血饮联合西利宾胺能明显改善脂肪肝模型大鼠的肝脏病理情况,减轻肝脏的脂肪变性,降低血清中ALT、AST、TG和T-CH含量,降低体重,降低瘦素水平及改善胰岛素抵抗指数,且均明显优于单用中药或西药的治疗组。结论:消脂活血饮联合西利宾胺治疗酒精性脂肪肝的机理可能与其降低血脂,减少肝脏脂肪沉积,保护肝细胞,改善肝脏微循环有关。第四部分为研究治疗进展。从中医和西医两个方面,对近年来众多学者和专家从不同角度研究和治疗酒精性脂肪肝进行了综述。现代医学治疗酒精性脂肪肝除了戒酒、对症治疗外,尚无特殊方法。中医药治疗酒精性脂肪肝,不论是分期治疗、辨证治疗或专药专方治疗,均有较好疗效,初步显示了其潜在优势,综合国内外酒精性脂肪肝的研究现状,目前中医中药治疗酒精性脂肪肝临床上缺乏对照大宗病例的前瞻性研究和现代医学检测手段(生化、免疫、B超甚至肝活检等);在实验研究方面亟待开发良好稳定的酒肝模型,观察指标比较单一,甚至重复、雷同等。因此尽快完善临床研究规范,深入开展实验研究,特别是细胞水平的研究,筛选临床重复性好、疗效高的方药,并进行药理药性研究,在此基础上提其有效成份,开展研究临床应用简便、高效的新剂型,是当前迫切需要开展的工作。我们在扶脾活血化浊研究课题中,将89例研究样本按照中医症候分为脾虚湿痰型、湿热内结型、肝郁气滞型、气滞血瘀型、痰瘀互结型、阴虚热结型6型,结合B超检查情况,发现肝郁气滞型酒精性脂肪肝最多见,42例,占研究样本的47.2%,临床以轻度脂肪肝为主,占此型的57.1%;脾虚湿痰型次之,21例,占研究样本的23.6%,临床以中度脂肪肝为主,占此型的81.0%;痰瘀互结型10例,约占总数的11.2%,临床以重度脂肪肝为主,占此型的60%。以上三型占研究样本总数的82.0%。其他中医证型16例,所占比例较少。可见,绝大多数AFL患者辨证有脾虚、气滞、痰浊、瘀血病理因素存在。从临床疗效看,中药组30例临床治愈和有效的19例患者均为肝郁气滞证、脾虚湿痰证、湿热内结证、气滞血瘀证、痰瘀互结证,表明中药“消脂活血饮”具有疏肝健脾,化浊祛瘀的功效,主要适应证为肝郁气滞、脾虚湿痰、痰瘀互结型,尤其对AFL肝郁气滞、脾虚痰瘀兼夹的证患者临床疗效较好,而对其它证型疗效相对不理想,不是AFL的唯一治法。辨证论治是中医学之精髓,临证抓住AFL患者脾虚痰瘀这一基本病机演变规律,施以扶脾活血化浊之法,用中药“消脂活血饮”治疗取得了较好的临床疗效,这也揭示了中医临床辨证施治的重要性。本研究为临床治疗提供了一种新的途径与方法,值得进一步研究和推广。更多还原

【Abstract】 Alcoholic fatty liver (AFL) is the result of alcohol intake caused by lipid accumulation in liver cells more than 5% of liver wet weight of liver. it is the most common clinical For clinical treatment of this study provides a new way and method, is worthy of further research and extension. It is most early alcoholic liver disease (ALD) one. In China, alcohol-induced liver disease has become second cause of hepatitis, and along with increasing people’s living standards, increasing the number of alcohol, alcoholic liver disease are rapidly increasing, it has become another serious public issue. In addition to modern medical treatment of alcoholism, there is no specific therapy without symptomatic treatment, In view of this status, under the guidance of our instructors, we research on alcoholic fatty liver theoretical, clinical and experimental problems. from the four aspects of a more detailed and systematic study.The first part was to explore traditional Chinese medicine theory. Firstly, the alcohol made the occurrence of fatty liver and physical endowments, and also link to weak spleen and stomach, excessive drinking, diet and other factors. The weakness and diet irregularly may affect the occurrence of the disease, and the prognosis, while excessive drinking is the direct cause of this disease. Secondly, spleen deficiency and loss of transportation is the intrinsic disease-oriented basis, phlegm and blood stasis among pathological changes became the key to this disease, loss of health delivery spleen, liver qi catharsis deficiency, heat of spleen and stomach, endogenous phlegm, qi-stagnancy and blood stasis, which eventually led to stagnation of qi, phlegm, blood stasis, plot in flank, disease in the liver and spleen, and kidney-related. Its pathogenesis can be summarized as loss of liver qi catharsis, blood stasis; spleen dysfunction, Shenqi deficiency. Third, a help for the treatment of spleen Huazhuo Huoxue Dafa, the disease is asthenia in origin and not asthenia in superficiality, it surely should tonify spleen, activate blood circle and resolve the phlegm.The second part of clinical research. Objective: To observe the effects of SilibinMeglumine Tablets with Xiaozhi Huoxue treating alcoholic fatty liver (AFL). Methods: 89 cases of alcoholic fatty liver patients were randomly divided into three groups, which combines group 1, Western and Chinese medicine treatment group 29 cases, group 2, 30 cases of Chinese medicine group, group 3, 30 cases of western medicine group, three groups of patients were received treatment combined with a variety of oral vitamin. Group1 with Western medicine and Huoxue Xiaozhi liquor, group2 was given Huoxue Xiaozhi alone; group3 SilibinMeglumine Tablets. And evaluate the efficacy of three groups. Results: The combination of Chinese and Western medicines clinically cured 29 cases of group 12 cases, 15 cases of effective and ineffective in 2 cases, total effective rate of 93.1%. Chinese medicine in 30 cases of group six cases of clinically cured, 12 cases of valid and invalid in 12 cases, total effective rate of 60.0%. Western medicine group of 30 cases of clinical cure in 6 cases, 11 cases of valid and invalid in 13 cases, total effective rate of 56.7%. Efficient compared three groups there was a significant difference significance, P <0.05. Conclusion: group1 was comprehensively effective than western medicine and Chinese medicine alone, with significant improvement in clinical symptoms and reduce the effects of blood lipids.The third part is about experimental study. Objective: To investigate the mechanism of Xiaozhi Huoxue liquor combined with SilibinMeglumine treating alcoholic fatty liver. Methods: rats with alcoholic fatty liver were randomly divided into normal control group, the experimental model group, treatment group of Chinese medicine, Western medicine in the treatment group and western medicine combined group, respectively, observed rat serum lipids, liver body weight ratio liver pathological changes, insulin resistance and leptin. Results: SilibinMeglumine combined with Xiaozhi Huoxue liquor can improve liver pathological circumstances in fatty liver rat model, reducing liver steatosis, lowering serum ALT, AST, TG and T-CH content, lowering weight, lowering leptin levels and improving insulin resistance index, we found that there was significantly superior to traditional Chinese medicine or Western medicine alone in the treatment group. Conclusion: Xiaozhi Huoxue liquor combined with SilibinMeglumine may be related to lipid lowering to reduce liver fat deposition, protecting liver cells and improve the microcirculation of the liver. The fourth part is about the progress of the treatment. From two aspects, Chinese medicine and Western medicine, in recent years many scholars and experts from different point of view and treatment of alcoholic fatty liver are reviewed. Modern medical treatment of alcoholic fatty liver in addition to alcohol, symptomatic treatment is concerned. Chinese medicine in treatment of alcoholic fatty liver, regardless of the treatment is implemented uptodate, differentiation or post-treatment drug treatment professionals have better efficacy, the initial indications of its potential advantages, comprehensive domestic and foreign alcoholic fatty liver study of the status, the current Chinese medicine alcoholic fatty liver treatment of clinical cases is lack of the bulk of the forward-looking research and methods of modern medical science (biochemistry, immunology, B-and even liver biopsy, etc.); in experimental studies it is need to develop a stable good wine liver model, compared observed single, or even repeat the same and so on. Therefore improving the clinical research norms as soon as possible, in-depth research carried out experiments, in particular the cellular level of research, clinical screening of good reproducibility, high efficacy of herbs and herbal pharmacology studies, on the basis of their active ingredients mentioned, simple clinical application of research and efficient new forms, is an urgent need for work.In our project of Huazhuo Huoxue tonifying spleen research, 89 cases in accordance with traditional Chinese medicine is divided into deficiency syndrome of phlegm and damp, heat and humid, stagnation of liver Qi, stagnation of Qi and blood stasis,phlegm and blood stasis, Yin deficiency. combined with B-ultrasound, we found that stagnation of liver Qi stagnation is the most prevalent, which 42 cases of alcoholic fatty liver, accounting for 47.2 percent. mild fatty liver, accounting for 57.1% of this type; syndrome of spleen deficiency and phlegm damp followed by 21 cases, accounting for 23.6 percent of the sample, moderate fatty liver, accounting for 81.0% of this type; syndrome of phlegm and blood stasis 10 cases, accounting for 11.2 percent of the total number, clinical to severe fatty liver, accounting for 60% of this type. All the cases accounted for more than 82.0 percent of the total number of samples. Other 16 cases, the less proportion. This shows that the vast majority of patients with AFL have a spleen deficiency Syndrome, Qi stagnation, phlegm, blood stasis disease factors. From the clinical efficacy, 19 cases in group 1 with effective fell into syndrome of liver depression qi stagnation, spleen phlegm and damp, hot and humid, liver qi stagnation and blood stasis, phlegm and blood stasis that traditional Chinese medicine "Xiaozhi Huoxue liquor" with loosening liver qi and tonifying spleen, Huazhuo Quyu effectiveness, the main indication for liver depression qi stagnation, spleen damp and phlegm, phlegm and blood stasis of AFL in particular, stagnation of liver Qi stagnation, blood stasis and spleen deficiency clinical efficacy in patients were good, and the effect of other type was not ideal. Treatment is of the essence of Chinese medicine, seizing the AFL in patients with clinical deficiency blood stasis of the basic pathogenesis of the evolution of the law, help to expose the Huazhuo Huoxue tonifying spleen, using traditional Chinese medicine to obtain a better clinical efficacy. This also prompted the importance of diagnosis.For clinical treatment, this study provides a new way and method, is worthy of further research and extension.更多还原