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肝硬化肝失疏泄的表现特点及其与微观指标的相关性研究
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摘要
“肝主疏泄”是中医肝的重要生理功能。根据中医理论,分析肝硬化的发生与发展,存在着中医肝主疏泄功能的异常。本研究拟从文献回顾与前瞻性临床调查两个方面,通过回顾性总结与前瞻性观察肝硬化病人的宏观表现与微观指标的变化及其相关性,分析本病肝失疏泄的常见宏观表现与微观指标(相关实验室及影像学指标)之间的联系,为进一步从病理表现探讨肝主疏泄生理功能的现代科学内涵提供一定依据。
     第一部分文献研究
     目的
     通过现代文献研究,分析肝硬化的中医辨治特点、常见中医证候及其与肝功能指标的相关性,梳理、归纳肝硬化肝失疏泄的表现特点及其与微观指标的关系。
     方法
     1.通过文献检索,选取具有明确肝炎肝硬化(包括乙型肝炎肝硬化和丙型肝炎肝硬化)的西医诊断、中医辨证分型、中医症状与中医治疗内容,并包含具有明确处方用药记录的有效典型病例报道,总结肝炎肝硬化的常见症、证及治疗方药。
     2.通过文献检索,选取具有明确肝硬化(包括不分型的肝硬化、肝炎肝硬化)西医诊断与中医辨证,肝硬化中医辨证分型下有肝功能指标具体数据的临床研究的文献报道,梳理、归纳肝硬化不同中医证候下肝功能指标的变化趋势。
     结果
     1.常见症状:①代偿期为脉弦、胁痛、乏力、苔腻、腹胀、苔薄、脉细、苔黄、苔白、面色晦暗、脾大、舌色红、纳呆、便溏、舌色暗等;②失代偿期为腹部膨隆、尿少、脉弦、腹水、下肢浮肿、腹胀、脉细、乏力、苔白、苔腻、腹露青筋、便溏、消瘦、神疲、蜘蛛痣等。两期均有肝失疏泄后导致的肝经循行部位异常表现如胁痛等,协助脾胃运化功能失常表现如腹胀、纳呆、便溏等。
     2.常见证候:①代偿期为肝郁脾虚、气滞血瘀、湿热蕴结、肝肾阴虚、肝郁血瘀、肝郁气滞、肝胆湿热、气阴两虚、血瘀、肝络瘀阻、脾虚、气虚血瘀;②失代偿期为水湿内停、气滞血瘀、肝郁脾虚、湿热蕴结、脾肾阳虚、肝肾阴虚、脾虚湿困、肝脾血瘀、水停、血瘀水停。两期证候均包含有肝失疏泄导致的肝气郁结,气机不调表现的证候类型如肝郁脾虚等,以代偿期更为明显。
     3.常见证候要素:①代偿期:病位类证候要素为肝、脾、肾,病性类证候要素为血瘀、气滞、气虚、湿热、阴虚;②失代偿期:病位类证候要素为脾、肝、肾,病性类证候要素为血瘀、水停、气滞、湿阻、气虚。两期证候要素均包含气滞、血瘀,是肝失疏泄、气机郁结、气血运行失常、血行障碍的表现。
     4.常用治疗药物:①代偿期:党参、太子参、西洋参、当归、白芍、栀子、知母、黄芩、黄连、黄柏、土鳖虫、桃仁、红花、郁金、延胡索、川芎、姜黄、五灵脂、半夏、杏仁、陈皮、枳壳、香附、川楝子;②失代偿期:白术、黄芪、人参、山药、车前子、车前草、茵陈、虎杖、茯苓、泽泻、猪苓、泽兰、益母草、葶苈子、桑白皮、大腹皮、防已、桂枝、三七、白茅根、厚朴、砂仁、苍术、牵牛子、甘遂、商陆、附子、干姜、肉桂、槟榔。两期均为常用药物的为鳖甲、丹参、莪术、穿山甲、柴胡、牡蛎、大黄、鸡内金。两期用药以疏肝解郁、行气止痛、理气活血的基本治则,为肝主疏泄理论指导临床用药的体现。
     5.配伍核心药物:①代偿期:白术、茯苓、丹参、党参、白芍、当归、鳖甲、郁金、桃仁、柴胡;②失代偿期:白术、茯苓、大腹皮、黄芪、丹参、泽泻、猪苓、当归、鳖甲、党参。两期核心药物体现疏肝、健脾、理气、化瘀的治则,进一步体现了肝主疏泄理论在肝硬化临床治疗中的应用。
     6.常见证候与肝功能指标的相关性:肝硬化肝气郁结、肝郁脾虚等证候的蛋白合成功能相对较好,但丙氨酸氨基转移酶、天门冬氨酸氨基转移酶、碱性磷酸酶、γ-谷氨酰转肽酶、总胆汁酸有一定程度的升高。
     结论
     1.肝炎肝硬化两期症状有联系也有不同,都存在肝失疏泄,气机阻滞的相关表现及相关证候证候类型,并以代偿期更为明显,而失代偿期在气滞基础上进一步发展,出现血瘀、水停等表现。
     2.肝硬化患者常有肝失疏泄的证候表现,这些证候与肝脏代谢功能、肝脏细胞受损程度之间存在一定的联系。
     第二部分临床研究
     目的
     通过全国多中心、大样本的横断面流行病学凋查,收集肝炎肝硬化患者的宏观表现(四诊信息等)及微观指标(相关实验室及影像学指标),比较代偿期与失代偿期的宏观表现与微观指标的差异,并运用因子分析和相关分析方法,分析肝炎肝硬化肝失疏泄的常见表现及其与微观指标的相关性,为基于本病进一步探讨肝主疏泄的科学内涵提供一定依据。
     方法
     1.运用课题组统一制定、印制的肝炎肝硬化临床信息采集表,通过严格的质量控制进行全国多中心、大样本的横断面流行病学调查,采集肝炎肝硬化患者的信息。
     2.采用课题统一数据录入管理平台建立数据库,并完成双人、双机独立录入,应用SPSS17.0统计软件包对数据进行统计分析。
     3.对肝炎肝硬化代偿期与失代偿期的症状表现与微观指标进行比较。
     4.选取肝炎肝硬化肝失疏泄相关症状,进行因子分析,并与微观指标进行相关性分析。
     结果
     1.常见症状:①代偿期:乏力、肝掌、急躁易怒、面色晦暗、腰膝酸软、口咽干燥、神疲、胃脘胀满、肌肤干燥、烦躁、目涩、胁胀、抑郁、失眠、太息等;②失代偿期:乏力、面色晦暗、肝掌、神疲、腹胀、胃脘胀满、尿色深黄、口咽干燥、纳呆、肌肤干燥、懒言、腰膝酸软、厌油腻、抑郁、急躁易怒等。两期均有肝失疏泄,肝本经循行部位不适的胁胀、太息、胸闷等表现,肝调畅情志功能失常的急躁易怒、抑郁、烦躁、焦虑等表现以及肝协助脾胃运化功能失常的腹胀、胃脘胀满、纳呆等表现。
     2.代偿期与失代偿期的症状分布比较:有明显统计学差异者为神疲、乏力、懒言、消瘦、发热、浮肿、面红、面色黄黑、面色晦暗、胁胀、胁痛、胃脘胀满、腹胀、腹痛、纳呆等症,其中急躁易怒、胁胀、胁痛、胃脘胀满、腹胀、纳呆等均为肝失疏泄,气机失调的代表症状。其中肝失疏泄表现为肝气郁于本经导致的胁胀、胁痛,肝调畅情志功能失常导致的急躁易怒等症以代偿期为明显,而肝协助脾胃运化功能失常导致的胃脘胀满、腹胀、纳呆等症以失代偿期为明显。
     3.代偿期与失代偿期微观指标的比较:两期微观指标在造血功能、凝血功能、肝功能、脂质代谢、肾功能、电解质平衡、血氨代谢、肝脏体积、脾脏体积、血管内径、血管流速、肝脏硬度以及神经内分泌方面的大部分指标都有明显的差异,应与肝失疏泄的临床表现间存在一定相关性。
     4.肝失疏泄相关表现与微观指标之间的相关性:肝的疏泄功能与机体造血、凝血、肝脏合成与代谢功能、血脂代谢、肾功能、电解质、血氨代谢、肝脏纤维化程度、肝脏及脾脏形态以及神经内分泌功能存在一定的相关性。
     结论
     1.肝炎肝硬化代偿期与失代偿期患者均有肝失疏泄的典型临床表现。代偿期患者以肝本经气机郁结、肝经循行部位不适与情志调节功能异常表现更为明显,而失代偿期患者以脾胃运化功能减弱为主要表现。同时两期所测的大部分微观指标存在明显差异,提示肝失疏泄的不同表现可能具有不同的病理生理学基础。
     2.肝失疏泄在肝炎肝硬化患者的主要表现在气机失调、情志异常与脾胃运化功能失常三个方面,当患者表现为肝失疏泄不同功能失常表现及不同症状,与不同的微观指标之间具有一定的相关性。
Liver controlling dispersion is an important function of liver in the theory of TCM. The function plays an important role in the process of development of cirrhosis.This paper includes literature and clinical study. Through the tansformations of the symptoms and micro index of cirrhosis, find the correlation between them. Then find the symptoms and micro index of liver dysfunction of TCM to explain the theory of liver controlling dispersion.
     Part1Literature Study
     Objective
     To analysisi the characteristics of TCM syndrome differentiation and the correlation between common TCM syndromes of cirrhosis and liver function indicators based on neoteric literature.
     Methods
     1Select effective cases of hepatitis cirrhosis according to the inclusion criteria on the basis of review of literatures published between1991and2010in the databases.
     2Select effective clinical reports of cirrhosis according to the inclusion criteria on the basis of review of literatures published between1991and2010in the databases.
     3To summarize the common symptoms, syndromes and the TCM prescriptions and medicine of the hepatitis cirrhosis cases.
     4To investigate the correlation between common TCM syndromes of cirrhosis and liver function indicators.
     Results
     1Common symptoms in the compensated cirrhosis are pulse string, hypochondriac pain, weakness, greasy coating, abdominal distention, thin coating, pulse thready, yellow fur, white fur and etc. In the decompensated cirrhosis are abdominal bulge, oliguria, pulse siring, ascites, edema of lower limbs, abdominal distention, pulse thready, weakness and etc. Hypochondriac pain, abdominal distention, anorexia and loose stool which arc the manifestations of liver dysfunction appear in both periods of hepatitis cirrhosis.
     2Common syndromes in the compensated cirrhosis arc depressed liver and deficient spleen, Qi stagnation and blood stasis, damp-heat, liver and kidney deficiency, liver depression and blood stasis and etc. In the decompensated cirrhosis are water and dampness retention, Qi stagnation and blood stasis, depressed liver and deficient spleen, damp-heat, spleen-kidney-yang deficiency and etc. The syndrome of depressed liver and deficient spleen are appearing in the two periods and obvious in compensated cirrhosis.
     3Common syndrome key factors in the compensated cirrhosis are liver, spleen, kidney, blood stasis, Qi stagnation, Qi deficiency, damp-heat and yin deficiency. In the decompensated cirrhosis are spleen, liver, kidney, blood stasis, water retention, Qi stagnation, damp obstruction and Qi deficiency. The syndrome key facors of Qi stagnation and blood stasis are results from qi-movement disturbance and qi-blood imbalance.
     4Taking the common occurrence frequency of equal to or greater than20%as the inclusion criteria, the main components of Chinese herb compound for compensated hepatitis cirrhosis were Baizhu(rhizome), Danshen(salvia), Baishao(radix paeoniae alba), Danggui(angelica), Chaihu(radix bupleuri), Yujin(turmeric), Biejia(turtle shell), Dangshen(codonopsis pilosula), Fuling(poria cocos) and Taoren(peach kernel), and for decompensated hepatitis cirrhosis were Baizhu(rhizome), Fuling(poria cocos), Dafupi(areca peel), Danshen(salvia), Zexie(rhizome alismatis), Huangqi(bupleurum), Zhuling(agaric), Biejia(turtle shell), Danggui(angelica) and Dangshen(codonopsis pilosula). The principle of treatment is reliefing liver for smooth basing on the theory of liver controlling dispersion.
     5The hepatic depression syndrome patients had light abnormal liver function. Their liver function indicators of ALT, AST, ALP, GGT and TBA go up somehow. Conclusions
     1There are some syndromes and symptoms caused by liver-qi stagnation in both compensated and decompensated cirrhosis and obvious in compensated cirrhosis.
     2There is some association between liver dysfunction syndromes of cirrhosis and the liver function indicators.
     Part2Clinical Study
     Objective
     Through the investigation of clinical symptoms and micro index of hepatitis cirrhosis, comparative analysis, factor analysis and correlation analysis, discuss the correlation between liver dysfunction's performance characteristics of hepatitis cirrhosis and micro index.
     Methods
     1The national multi-centers and big sample clinical epidenmiology investigation of hepatitis cirrhosis was developed on strice quality control.
     2Established the database of clinical epidemiology investigation of hepatitis cirrhosis.
     3Through methods of comparative analysis, analyze the symptoms and micro index difference between compensated and decompensated cirrhosis.4Through methods of factor analysis and correlation analysis, analyze the correlation between liver dysfunction's performance characteristics of hepatitis cirrhosis and micro index.
     Results
     1Common symptoms in the compensated cirrhosis are weakness, liver palms, anxiety and irritability, gloomy complexion, soreness and weakness of waist and knees, dry mouth and pharynx, fatigue, stomach distention and etc. In the decompensated cirrhosis are weakness, gloomy complexion, liver palms, fatigue, abdominal distention, stomach distention, deep yellow urine, dry mouth and pharynx and etc. Rib-side distention, sighing, choking sensation in chest, depression, anxiety, abdominal distention and anorexia which are the manifestations of liver dysfunction appear in both periods of hepatitis cirrhosis.
     2Some symptoms have significant differences in compensated and decompensated cirrhosis. They are fatigue, weakness, laziness to speak, emaciation, fever, edema, flushing, gloomy complexion, rib-side distention, hypochondriac pain, stomach distention, abdominal distention, abdominal pain, anorexia and etc. The symbol symptoms of stagnation of liver qi and sentiment abnormality are obvious in compensated cirrhosis. The symbol symptoms of incoordination between spleen and stomach are obvious in decompensated cirrhosis.
     3Most of the micro index has significant differences in compensated and decompensated cirrhosis because of the illness growing worse sunch as the the index of hcmatopoicsis, coagulation, liver function, dyslipidcmia, renal function, electrolyte disturbance and etc. which are related to the manifestations of liver dysfunction.
     4The liver dysfunction is related to the index of hematopoiesis, coagulation, liver function, dyslipidemia, renal function, electrolyte disturbance and etc.
     Conclusions
     1The stagnation of liver qi and sentiment abnormality of compensated cirrhosis is more obvious.The incoordination between spleen and stomach of decompensated cirrhosis is more obvious.The different liver dysfunction's performance characteristics of hepatitis cirrhosis has different pathophysiological basis.
     2The liver dysfunction's performance characteristics of hepatitis cirrhosis are mainly stagnation of liver qi, sentiment abnormality and incoordination between spleen and stomach. The three parts respectively have relationship with different micro index.
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