肠源性内毒素血症与肝病

肠道内有大量细菌生长,如细菌过度繁殖,内毒素产生过量,或肠黏膜屏障受损内毒素吸收入门静脉增多,或肝内Kupffer细胞吞噬功能低下,内毒素的吸收量超过了肝脏的清除能力,内毒素即可“泛滥”（spillover）进人体循环而形成内毒素血症。     

口服乳果糖对肝病肠源性内毒素血症及细胞因子的影响

我们的目的了解乳果糖对肝病肠源性内毒素血症（ｅｎｄｏｔｏｘａｅｍｉａ,ＥＴＭ）治疗作用,并探讨细胞因予变化与ＥＴＭ的关系。一、资料与方法１．研究对象：急性肝炎２８例,慢性肝炎３２例,肝硬化２９例,男５６例,女３３例,平均年龄４３．５岁,诊断根据１９９５年北京第五次全国传染病寄生虫学术会议制订的病毒性肝炎方案标准。各病例纠随机分为两组,在常规护肝的基础上,一组口服乳果糖,另一组不服乳果糖。乳果糖剂量１０～３０ｇ／ｄ,并调节至大便２～３次,疗程为２０ｄ,并分别于入院后次日及２０日常规抽血检测。２．内…     

重型肝炎与肠源性内毒素血症

近年来,肠源性内毒素血症(intestinal endo-toxemia,IETM)与肝脏疾病之间的关系逐渐引起人们的关注。动物研究已经证实在各种实验性肝脏疾病均伴有IETM的发生,而且临床观察也显示在重型肝炎患者出现严重IETM的发生率高达80%～100%[1]。随着研究的深入,IETM在肝病患者的发生、发展、损伤机制及治疗方面都出现了一些新的理论和方法,同时也面临许多问题,本文将就此作一综述。内毒素的来源一般认为重型肝炎时内毒素主要来源于肠道菌群。正常情况下肠道菌群对许多外来物质的吸收起重要作用,但当某些疾病导致肠道菌群失调或移位时,产生的有…     

肠源性内毒素血症与肝病

多种肝炎与肝病大多伴有肠源性内毒素血症(IETM)。肝病患者的临床表现与IETM密切相关,韩德五教授领导的山西医科大学肝病研究所2 0余年来围绕IETM与肝病进行了深入而系统的研究,在大量动物实验与临床研究基础上提出了新的观点和理论:①各种肝炎是通过各自的病因及其发病机制所造成的肝损伤(称之为“原发性肝损伤”)。原发性肝损伤往往伴有IETM ,后者通过过度或持续激活枯否细胞所释放的细胞因子、炎性介质、自由基等又损伤了肝组织,这种肝损伤称之为“继发性肝损伤”。肝炎、肝病患者的临床表现是这两种肝损伤的叠和;②由于IETM过度…     

肝硬化患者内毒素调节蛋白与肠源性内毒素血症关系

肝硬化患者多伴有肠道细菌过度生长、通透性增加及细菌移位,腹水一旦形成常伴有高动力循环状态,进而导致肠源性内毒素血症(IETM),我们检测了肝硬化患者血清内毒素结合蛋白(LBP)水平,探讨其与IETM的关系,现将结果报告如下。     

肝病与内毒素血症

近年来众多资料表明,各型急性病毒性肝炎的内毒素血症发病率为39%～64%,慢性肝病的内毒素血症发病率为50%,肝硬化时则高达79%。肝病时肝功能受损,肝脏失去屏障功能,使肠道G~-菌代谢所释放内毒素不能被清除,进入全身体循环而产生内毒素血症。其发生机制认为与下列因素有关。     

肠源性内毒素血症与肝功能衰竭

肠源性内毒素血症与肝功能衰竭山西医学院肝病研究所韩德五关于肝功能衰竭的概念至今还不甚明确和统一。往往将肝性昏迷与肝功能衰竭相混同，其实肝功能衰竭是包括肝性昏迷在内的一个临床综合征。另外，一般都把肝功能衰竭看作是肝实质细胞严重破坏的结果。肝实质细胞的功...     

肝硬化时肠源性内毒素血症形成机制的研究进展

大量实验证实,多种肝病尤其是慢性肝病不同程度伴随肠源性内毒素血症（intestinal endotoxemia,IETM）,其中肝硬化患者IETM的发生率为79．0％～92．0％,肝功能损害越重,内毒素水平越高。肝硬化时肠道菌群失调,肠黏膜屏障功能减低,肝脏清除内毒素能力下降,内毒素水平升高,IETM发生率增加,IETM形成后进一步加重肝脏损伤,导致肝硬化患者感染、腹水、上消化道出血、肝肾综合征、肝性脑病等并发症的发生,两者之间形成恶性循环。现将目前关于肝硬化时IETM形成机制的研究进展综述如下。     

中西医治疗肝病肠源性内毒素血症的研究进展

近年来,肠源性内毒素血症与肝病的关系日益受到重视。资料表明各型肝病内毒素血症的发生率分别为:重型肝炎58％～100％,肝硬化79％～92％,慢性肝炎50％～58％,急性肝炎16％～43％。虽对各型肝病患者肠源性内毒素血症发生率报道不一,但肝病存在程度不等的肠源性内毒血症已得到公认,其可加重肝损害及促发各种并发症并与肝病互为因果。为此,广大中西医学者在探讨内毒素所致肝损伤机理以及寻找治疗肝病肠源性内毒素血症的中西医药方面进行     

肠源性内毒素血症与肝功能衰竭

肠源性内毒素血症(intestinal endotoxemia, IETM)与肝功能衰竭的关系日益受到重视,资料显示,病毒性肝炎患者的35％～65％伴有IETM的发生,重症肝炎患者IETM的出现率为70％～100％,肝硬化则达79％,由此可见,肝损伤时容易形成IETM,而IETM形成后,进入肝脏的内毒素又可引起肝细胞的一系列损伤反应,使肝损伤不断加重,最后走向肝功能衰竭。     

肝病患者内毒素血症的临床意义

目的探讨四种肝病内毒素血症（ｅｎｄｏｔｏｘｅｍｉａ,ＥＴＭ）的发生率及其临床意义方法１９９７－０２／１９９８－０６山西医科大学第一医院传染病科住院的急、慢性肝炎、肝炎肝硬变及重症肝炎患者３２０例采用基质显色法鲨试验定量检测血浆内毒素（ｅｎｄｏｔｏｘｉｎ,ＥＴ）水平,应用放射免疫分析法测定血浆肿瘤坏死因子（ｔｕｍｏｒｎｅｃｒｏｓｉｓｆａｃｔｏｒＴＮＦ）水平,采用琼脂单向免疫扩散法测定血浆纤维连接蛋白（ｆｉｂｒｏｎｅｃｔｉｎ,Ｆｎ）含量,采用速率法在全自动生化分析仪．上测定血浆丙氨酸转氨酶（ａｌａｎｉｎｅ　ａｍｉｎｏｔｒａｎｓｆｅｒａｓｅＡＬＴ）活性．结果肝病患者血浆ＥＴ,ＡＬＨ,ＴＮＦ含量明显高于健康对照组（Ｐ＜０．０１）,而在肝炎肝硬变、重症肝炎组Ｆｎ含量均明显低于对照组重症肝炎、肝炎肝硬变、慢性肝炎、急性肝炎患者肠源性内毒素血症（Ｉｎｔｅｓｔｉｎａｌｅｎｄｏｔｏｘｅｍｉａ,ＩＥＴＭ）发生率分别为９３．３％,８４．３％,７９．０％与７５．０％．结论肝病患者长期持续存在的ＩＥＴＭ可加剧肝细胞损伤,在急性肝炎重症化与慢性化中均具有其重要作用     

Intestinal endotoxemia as a pathogenetic mechanism in liver failure

Liver injury induced by various pathogenic factors(such as hepatitis virus,ethanol,drugs and hepatotoxicants,etc.)through their respective special pathogenesis is referred to as“primary liver injury”(LPS)and the activation of kupffer cells by LPS while intestinal endotoxemia(IETM)occurted during the occurrence and development of hepatitis is named the“secondary liver injury”(SLI).The latter which has lost their own specificities of primary pathogenic factors is ascribed to IETM.The“secondary liver injury”is of important action and impact on development and prognosis of hepatitis.More severe IETM commonly results in excessive inflammatory responses,with serious hepatic necrosis,further severe hepatitis and even induces acute liver failure.The milder IETM successively precipitates a cascade,including repeated and persistent hepatocytic impairment accompanied by infiltration of inflammatory cells,hepatic fibrosis,cirrhosis and hepatocarcinoma.Generally,the milder IETM ends with chronic hepatic failure.If PLI caused by various pathogenic factors through their independent specific mechanismis regarded as“the first hit”on liver,then SLI mediated by different chemical mediators from KC,activated by IETMin the course of hepatitis is “the second hit”on liver.Thus,fusing and overlapping of the primary and scorndary liver injunies determine and influeuce the complexity of the illness and outcome of the patient with hepatitis.For this reason,the viewpoint of “SLI”induced by the “second hit”on liver inflicted by IETM suggests that medical professionals should attach great importance to both“PLI”and“SLI”caused by IETM.That is,try to adjust the function of KS,and eliminate endotoxemia ofthe patient.     

酒精性肝病患者肠道微生态变化研究进展

目的 酒精性肝病(ALD)是全球肝脏疾病相关死亡的重要原因之一,已经成为全球范围内的卫生健康负担。越来越多的证据证明饮酒、肠道微生物失调和肝脏疾病之间存在密切的联系,肠道屏障破坏导致细菌及其产物的移位是关键的致病因素。近年来,通过对饮酒、肠道微生态与ALD进展之间相互作用的研究越来越多,寻找新的生物标志物和治疗靶点也成为预防和治疗ALD的热点。     

Gut-derived endotoxemia: one of the factors leading to production ofcytokines in liver diseases

AIM To understand the relationship between levels of endotoxin and cytokines in serum and to clarify thecause of cytokines change in liver diseases.METHODS Serum endotoxin level was determined by quantitative limulus amebocyte lysate chromogenicassay in 89 cases of acute and chronic liver diseases. Cytokines (TNF-a, IL-2, IL-6, IL-8, G-CSF) wereassayed by ELISA. Patients were divided into two groups based on oral administration of lactulose or not.Mean concentration of endotoxin and cytokines was compared before and 20 days after lactulose treatment.RESULTS The highest serum level of endotoxin was found in patients with cirrhosis (69.3±23.6pg/mL)and the lowest in patients with chronic hepatitis (28.4±7.9pg/mL), the moderate in patients with acutehepatitis (44.6±14.3pg/mL) (P<0.01). Serum levels of TNF-a, IL-2, IL-6, IL-8, G-CSF were higher inpatients with acute hepatitis than those with chronic hepatitis (P<0.05). No difference was noted betweenchronic hepatitis and cirrhosis (P >0.05). In all cases, serum levels of endotoxin were positively correlatedwith the concentration of TNF-a (r=0.555, P<0.05), IL-6 (r=0.531, P<0.01), IL-8 (r=0.440,P<0.05) and G-CSF (r =0.440, P<0.05), but not with IL-2 (r =0.10l, P<0.05). The decrease of serumlevels of endotoxin was greater in patients taking lactulose than controls (25.6±14.4pg/mL, n = 49 cases vs.10.9±9.Spg/mL, n = 40 cases, P < 0.01), the recovery from endotoxemia was higher in group withlactulose treatment than in controls (94.7%, n = 19 vs 36.4%, n = 22, P < 0.01 ). The decrease ofendotoxin resulted in decreases of TNF-a, IL-6, IL-8, G-CSF, ALT, AST and TB.CONCLUSION Endotoxemia is common in liver diseases, which could induce production and release ofcytokine from monocytes and macrophages and has harmful effects on hepatocytes. Treatment with lactulosecould decrease serum levels of endotoxin and cytokines, suggesting that lactulose could protect liver cells frominjury by reducing the absorption of endotoxin in intestine.     

Intestinal virome: An important research direction for alcoholic and nonalcoholic liver diseases

In recent years, the interaction between the gut microflora and liver diseases has attracted much attention. The intestinal microflora is composed of bacteria, archaea, fungi and viruses. There are few studies on the intestinal virome, and whether it has a causal relationship with bacterial changes in the gut is still unclear. However, it is undeniable that the intestinal virome is also a very important portion of the blueprint for the development of liver diseases and the diagnosis and therapeutic modalities in the future.     

Intestinal microflora and metabolic diseases

Recent advances in molecular sequencing technology have allowed researchers to answer major questions regarding the relationship between a vast genomic diversity—such as found in the intestinal microflora—and host physiology. Over the past few years, it has been established that, in obesity, type 1 diabetes and Crohn's disease—to cite but a few—the intestinal microflora play a pathophysiological role and can induce, transfer or prevent the outcome of such conditions. A few of the molecular vectors responsible for this regulatory role have been determined. Some are related to control of the immune, vascular, endocrine and nervous systems located in the intestines. However, more important is the fact that the intestinal microflora-to-host relationship is bidirectional, with evidence of an impact of the host genome on the intestinal microbiome. This means that the ecology shared by the host and gut microflora should now be considered a new player that can be manipulated, using pharmacological and nutritional approaches, to control physiological functions and pathological outcomes. What now remains is to demonstrate the molecular connection between the intestinal microflora and metabolic diseases. We propose here that the proinflammatory lipopolysaccharides play a causal role in the onset of metabolic disorders.     

Intestinal physiology and parasitic diseases

This paper reviews the major steps in alimentation, digestion, and absorption, which must be intact as a basis for normal nutrition, and discusses evidence relating parasitic infection in humans to effects on intestinal physiology. Parasites, with their ability to induce systemic toxicity and fever, to release active and toxic substances into the intestinal lumen, to compete for certain nutrients, to cause both functional and structural changes in the intestinal mucosa, and to stimulate hypermotility, which lessens the time available for digestion and absorption, can influence the alimentary process a almost every one of its steps. However, parasitic infection is likely to exert its most important impact at the very first step of the alimentary process, by adversely affecting the intake of food through any of a variety of mechanisms.