肠黏膜屏障功能障碍在重症急性胰腺炎中的研究进展

重症急性胰腺炎(SAP)病情险恶、并发症多,且病死率高。过去几十年来,SAP发病率显著增加,SAP可导致肠道黏膜屏障损伤,从而引起细菌或内毒素易位,继而出现胰腺组织继发感染,导致全身炎症反应综合征(SIRS)及多器官功能障碍综合征,进而影响SAP患者的预后。在SAP发病过程中肠黏膜屏障损伤具有重要作用。因此,对肠道黏膜屏障功能障碍在SAP发病机制研究中尤为重要。现将重症急性胰腺炎肠黏膜屏障功能障碍的研究进展进行综述。     

不同营养方式对肠道缺血再灌注大鼠肠屏障功能的影响

目的探讨不同营养物质及支持途径对肠道缺血再灌注大鼠肠屏障功能和细菌易位的影响。方法60只雄性SD大鼠建立肠道缺血再灌注模型,随机分成普通肠外营养组(PN),富含谷氨酰胺的肠外营养组(G-PN),普通肠内营养组(EN)及免疫增强型肠内营养组(IEN)。从术后第1天起连续营养支持7d,各组等氮、等热卡。观察肠道形态学、肠道黏膜通透性、肠道细菌易位情况和血浆内毒素水平及肠道免疫功能检测。结果PN组肠黏膜明显萎缩,其绒毛高度、黏膜厚度、隐窝深度及绒毛表面积均显著低于其他各组(P<0.05);其肠黏膜通透性及内毒素值显著高于其他各组(P<0.05),细菌易位率(100%)明显高于其他各组(G-PN组60.0%,EN组33.3%,IEN组20.0%)。PN组CD4 T淋巴细胞和IgA 浆细胞分布显著低于其他各组(P<0.01)。结论EN在维护肠黏膜屏障功能、防止细菌及内毒素易位方面优于PN。免疫增强型EN在维护肠黏膜屏障、改善肠道免疫功能、防止细菌易位方面作用优于普通EN。     

肠屏障功能常用血清学检测现状及进展

肠屏障功能障碍（intestinal barrier dysfunction）是各种原因引起的肠黏膜损伤、萎缩,肠通透性增加,肠菌群失调,从而导致细菌和（或）内毒素易位,并可诱发和（或）加重全身炎症反应和多器官功能障碍。肠屏障功能障碍对危重疾病的发生、发展、转归有重要影响。肠屏障功能障碍在危重病患者中较常见,但目前尚缺乏较为客观的临床诊断标准与统一的治疗方案。肠道屏障功能的血清学检测是诊断肠道屏障功能障碍的重要依据,本文就近年来国内外常用的血清学检测的研究现状与进展进行综述。     

针灸治疗膝骨关节炎的作用机制研究

针灸治疗膝骨性关节炎虽可抑制炎症反应和延缓关节软骨退变，但其作用机制仍在探究中。现以肠道微生物介导的肠-关节轴为切入点，从经络脏腑理论分析，针灸可通过以下途径发挥治疗膝骨性关节炎的作用：调理气机升降；调节胃肠道动力，促进机体调节；调控肠道菌群平衡，使其恢复稳态；稳固肠黏膜机械屏障，维持肠道通透性。本文基于肠-关节轴理论，阐明针灸-肠道菌群-炎症反应之间具体作用机制，针灸可通过多通路、多靶点、双向性治疗膝骨关节炎，以期为针灸治疗膝骨性关节炎提供理论依据，为后期临床推广应用。     

肠道屏障功能临床评估方法

1 概述 研究已证实肠道是体内最大的"细菌库",当在创伤、手术、严重感染等条件下,肠道的微生物、内毒素通过肠黏膜侵入肠外组织,肠道菌群易位,导致全身炎症反应综合征(SIRS)甚至多脏器功能不全综合征(MODS).     

不良饮食习惯影响瘢痕疙瘩形成的研究进展

长期的不良饮食习惯可造成肠道菌群改变,使得内毒素/脂多糖大量生成,导致肠道黏膜通透性增加,激活大量炎症因子进入门静脉。此外,高碳水化合物饮食可增加肝脏代谢负担,促进线粒体氧化磷酸化,导致氧化应激,在ATP合成过程中产生新的脂肪,从而导致脂肪异位堆积,激活核因子κB信号通路,释放肿瘤坏死因子α、白细胞介素1β（IL-1β...     

胃癌术后早期炎症与肠道黏膜通透性的关系

目的探讨肠道黏膜通透性（D-乳酸含量）与外周血中内毒素含量和WBC计数之间的关系。方法胃癌行手术病人62例,检测术前和术后第1、3、7天的外周血中D-乳酸、内毒素、WBC计数水平并进行比较。结果术后第1天、第3天D-乳酸、内毒素及WBC计数均高于术前及第7天（P〈0．05）;术后第1、3、7天血清D-乳酸水平与内毒素之间均呈正相关。结论胃癌手术后第1天开始肠黏膜通透性增加,炎性反应明显,术后第3天达到高峰。肠道菌群易位与炎症反应有关。     

应用全身炎症模型研究细菌易位的途径,程度和时限

已证明细菌在某些病理情况下可以从肠道向全身器官转移,即细菌易位。但究竟由何途径易位及其发生的时间仍不甚明确。本实验应用不同剂量的酵母多糖致伤以激活补体系统并引起全身炎症,进而观察肠道细菌     

阻断肠道淋巴通道对重症急性胰腺炎大鼠肠道细菌易位的影响

肠道细菌易位是胰腺炎发生感染、促进全身炎症反应综合征(SIRS)和多器官功能障碍综合征(MODS),致重症急性胰腺炎(SAP)病人死亡的重要原因[1].但对SAP时细菌易位途径的认识尚未达成共识.该研究旨在探讨肠道淋巴通道途径在SAP致肠道细菌易位中的作用.     

重症急性胰腺炎胃肠动力障碍的研究进展

重症急性胰腺炎(SAP)胃肠道损伤，在其病理生理过程中起关键性作用，主要为胃肠动力功能障碍(其中麻痹性肠梗阻即胃肠功能衰竭占35％-58％)及胃肠黏膜受损。胃肠功能衰竭是治疗SAP的难点，常常发生在其他脏器衰竭之前。正常的胃肠蠕动可将进入胃的有害菌1h排入结肠，2h排出肠道。胃肠蠕动减弱或消失，肠道内细菌和毒素排泄障碍，肠道内细菌过度生长繁殖，造成菌群失调，引起细菌易位和毒素的吸收。在危重病的病理生理过程中，胃肠功能衰竭积极地参与了SIRS(全身炎症反应综合征)和MODS(多器官功能衰竭)的病理生理过程。     

Hypertonic resuscitation of hemorrhagic shock prevents alveolar macrophage activation by preventing systemic oxidative stress due to gut ischemia/reperfusion

BACKGROUND: The gut is a target organ of shock/resuscitation (S/R); however, it also contributes to distant inflammation through the generation of oxidants. S/R with antioxidants such as N-acetylcysteine (NAC) prevents lipopolysaccharide (LPS)-induced cytokine production and NF-kappaB activation in rat alveolar macrophages. Therefore, we hypothesized that hypertonic saline (HTS) might exerts its protective effect by preventing gut ischemia/reperfusion injury, thus decreasing oxidative stress and distant priming in alveolar macrophages. METHODS: A two-hit rat model of shock resuscitation was used. Plasma levels of 8-iso-prostaglandin, a marker of lipid peroxidation, was quantified by eicosanoid immunoassay with acetylcholinesterase kit. Gut histology with hematoxylin and eosin staining was performed 1 to 6 hours after resuscitation. Alternatively, alveolar macrophages from bronchoalveolar lavage (BAL) at end resuscitation were incubated in vitro with LPS (0.01 mug/mL), and NF-kappaB translocation was observed by immunofluorescent staining with anti-p65 antibody. RESULTS: HTS resuscitation prevented leukosequestration in the alveolar space, and it abrogated the progressive rise in blood 8-iso-prostaglandin production observed with Ringer's lactate (RL) resuscitation. Inhibition of oxidant stress with NAC corresponded with the ability of HTS to prevent S/R-induced edema, villus flattening, and mucosal sloughing in the mid-ileum. LPS-induced NF-kappaB translocation in alveolar macrophages after RL was 42% compared to 20% after HTS. Similar attenuation was observed with NAC resuscitation (16%). CONCLUSIONS: HTS resuscitation prevents systemic oxidative stress by reducing gut ischemia/reperfusion injury and consequently attenuates distant alveolar macrophage priming, thereby reducing LPS-induced NF-kappaB nuclear translocation in alveolar macrophages and organ injury. This represents a novel mechanism whereby HTS exerts its immunomodulatory effects.     

益生菌在急性胰腺炎治疗中应用的研究进展

急性胰腺炎（AP）是因胰腺中胰酶异常的激活而对胰腺自身以及周围器官产生消化而引起的，以胰腺局部炎症反应为主要特征，严重者可导致器官障碍的急腹症。在AP的进展过程中，微循环障碍会导致肠道的缺血缺氧进一步导致上皮的损伤，从而限制肠道菌群的平衡，影响基础的免疫系统。肠道屏障需要一个连续的细胞层以及基质连接。在AP发病过程中，这种肠道屏障的完整性破坏，引起肠道内菌群移位至其他器官以及有益菌的减少，对患者导致进一步伤害，从而导致全身炎症反应综合征（SIRS）、多器官功能障碍综合征（MODS）甚至死亡。近年来，国内外学者对于通过改善肠道内环境而减轻AP的发展日益关注，在AP患者治疗过程中，补充益生菌可以保护修复AP患者的肠道黏膜屏障，同时减少患者发生菌群异位机会，改善肠道内微生态，对AP的治疗提供了新的思路。     

Studies of the route, magnitude, and time course of bacterial translocation in a model of systemic inflammation

Bacteria have been documented to translocate from the gut to systemic organs, yet the exact route by which they translocate remains unclear. To determine the route of bacterial translocation, different dosages of zymosan were used to activate complement and cause systemic inflammation. At a zymosan dose of 0.1 mg/g, bacteria translocated only to the mesenteric lymph node complex, whereas at a dose of 0.5 mg/g the bacteria translocated systematically. In rats receiving 0.5-mg/g doses of zymosan, the bacteria appeared to reach systemic organs via the portal blood rather than via the mesenteric lymph, as bacteria were present in 87% of portal blood samples but only 25% of lymph samples. The number of bacteria exiting the portal vein was 11,500 times greater than the number exiting via the lymph. Thus, both the route and extent of bacterial translocation varies based on the magnitude of the inflammatory insult, with the portal blood being the major route of bacterial translocation to systemic organs.     

Pancreatitis and nutrition. Significance of the gastrointestinal tract and nutrition for septic complications

Septic complications are an important factor for the morbidity and mortality of acute pancreatitis. The gut has been identified as a source of infection early in the course of the disease allowing intestinal bacteria to translocate into pancreatic necrosis and other organs. Bacterial translocation is promoted by an impaired intestinal mucosal barrier which can be attributed to the reduced oxygen and substrate supply of the intestine during the early systemic response to the pancreatic injury. A rat model of severe acute pancreatitis has been used to confirm the hypothesis that an impaired mucosal barrier can be stabilized by supplying certain nutritients, vitamins and trace elements. Following a discussion of the many aspects of bacterial translocation and gut derived sepsis, the role of the gut and nutrition for the development of septic complications in acute pancreatitis is summarized as follows: Early in the course of acute pancreatitis the gut is a target organ of the primary systemic inflammatory response (SIRS) to pancreatic injury. SIRS-induced gut barrier dysfunction promoting bacterial translocation makes the gut the motor for secondary (septic) complications. As a septic focus the gut becomes a target for therapeutic measures aimed at stabilizing the impaired gut barrier. Nutritive factors demonstrated to improve impaired gut barrier function include early enteral feeding and specific factors like glutamine which are essential for enterocytes and colonocytes in stress. Experimental data are presented to underline the significance of these nutritive factors and subsequent randomized multicenter trials performed to verify the positive experimental results are introduced. The effect of other nutritive factors (e.g. omega-3-fatty acids) has not yet been systemically investigated. Thus, experimental and clinical studies need to be performed for evaluating their effect on bacterial translocation and the disease course in acute pancreatitis.     

Glutamine stabilizes intestinal permeability and reduces pancreatic infection in acute experimental pancreatitis

Intestinal barrier failure and subsequent translocation of bacteria from the gut play a decisive role in the development of systemic infections in severe acute pancreatitis. Glutamine (GLN) has been shown to stabilize gut barrier function and to reduce bacterial translocation in various experimental settings. The aim of this study was to evaluate whether GLN reduces gut permeability and bacterial infection in a model of acute necrotizing pancreatitis. Acute necrotizing pancreatitis was induced in 50 rats under sterile conditions by intraductal infusion of glycodeoxycholic acid and intravenous infusion of cerulein. Six hours after the induction of pancreatitis, animals were randomly assigned to one of two groups: standard total parental nutrition (TPN) or TPN combined with GLN (0.5 g/kg⁻¹/day⁻¹). After 96 hours, the animals were killed. The pancreas was prepared for bacteriologic examination, and the ascending colon was mounted in a Ussing chamber for determination of transmucosal resistance and mannitol flux as indicators of intestinal permeability. Transmucosal resistance was 31% higher in the animals treated with GLN-supplemented TPN compared to the animals given standard TPN. Mannitol flux through the epithelium was decreased by 40%. The prevalence of pancreatic infections was 33% in animals given GLN-enriched TPN as compared to 86% in animals receiving standard TPN (P < 0.05). Adding GLN to standard TPN not only reduces the permeability of the colon but decreases pancreatic infections in acute necrotizing pancreatitis in the rat. This confirms previous reports that GLN decreases bacterial translocation by stabilizing the intestinal mucosal barrier. The present findings provide the first evidence suggesting that stabilizing the intestinal barrier can reduce the prevalence of pancreatic infection in acute pancreatitis and that GLN may be useful in preventing septic complications in clinical pancreatitis.     

Endotoxin but not malnutrition promotes bacterial translocation of the gut flora in burned mice

Previously we have shown that under certain conditions, bacteria can pass through the intact epithelial mucosa to the mesenteric lymph nodes (MLN), liver, spleen, and bloodstream to cause infection, a process termed bacterial translocation. To extend these studies, we determined the influence of protein malnutrition and endotoxemia on bacterial translocation in burned (25% TBSA) and unburned mice. The results of these experiments documented that protein malnutrition did not promote bacterial translocation from the gut in either burned or unburned animals, although it did disrupt the normal indigenous gut flora. In contrast, a nonlethal dose of endotoxin (IP) promoted bacterial translocation to the mesenteric lymph nodes in burned and unburned mice, but only in burned mice did the bacteria translocate from the gut to other systemic organs (p less than 0.01). Furthermore, the mortality rate of mice receiving only endotoxin or burn was less than 10%, while the combination of endotoxin plus a thermal injury increased the mortality rate to 100% (p less than 0.01). These studies support the concept that bacteria may translocate from the gut to other organs and be a potential source of lethal infections after thermal injury.     

Effect of surgical manipulation of the rat intestine on enterocyte populations

BACKGROUND: The intestine is susceptible to operations at remote locations, and the barrier function is altered during intestinal manipulation, leading to bacterial or endotoxin translocation into the systemic circulation. One of the mainstays for the maintenance of the integrity of the barrier function is epithelial cell proliferation and migration. The present study looked at the effect of gut manipulation after laparotomy on different cell populations of the intestinal epithelium. METHODS: Surgical manipulation of the gut was performed by opening the abdominal wall and handling the intestine, as is done during laparotomy. Villus and crypt cells were isolated at different time periods after gut manipulation, and mitochondria were prepared from isolated enterocytes. The effects of surgical manipulation on enterocytes and isolated mitochondria were studied. RESULTS: Mechanical manipulation of the gut resulted in alterations in the intestinal epithelium, as shown by decreased cell viability and yield in the crypt cells. The alterations were associated with actin reorganization, as well as with altered cell proliferation and adenosine deaminase activity. At the mitochondrial level, altered mitochondrial function, such as decreased respiratory control ratio, increased 3-[4,5-dimethylthiazol-2-yl]-2,5 diphenyl tetrazolium bromide reduction, and induction of permeability transition in the crypt cells, was observed. These alterations were maximal 1 hour after surgical manipulation and partially recovered to normal by 24 hours. CONCLUSIONS: Mechanical manipulation of the gut that occurs during any abdominal operation induces alterations in the intestine, both at the cellular and the subcellular levels. The crypt cells bear the brunt of the damage, and the reversibility of the damage is possibly brought about by increased proliferation and movement of the cells.     

The crosstalk of gut microbiota and chronic kidney disease: role of inflammation,proteinuria, hypertension,and diabetes mellitus

Chronic kidney disease (CKD) has been shown to result in profound changes in the composition and functions of the gut microbial flora which by disrupting intestinal epithelial barrier and generating toxic by-products contributes to systemic inflammation and the associated complications. On the other hand, emerging evidence points to the role of the gut microbiota in the development and progression of CKD by provoking inflammation, proteinuria, hypertension, and diabetes. These observations demonstrate the causal interconnection between the gut microbial dysbiosis and CKD. The gut microbiota closely interacts with the inflammatory, renal, cardiovascular, and endocrine systems via metabolic, humoral, and neural signaling pathways, events which can lead to chronic systemic inflammation, proteinuria, hypertension, diabetes, and kidney disease. Given the established role of the gut microbiota in the development and progression of CKD and its complications, favorable modification of the composition and function of the gut microbiome represents an appealing therapeutic target for prevention and treatment of CKD. This review provides an overview of the role of the gut microbial dysbiosis in the pathogenesis of the common causes of CKD including hypertension, diabetes, and proteinuria as well as progression of CKD.     

Endotoxin promotes the translocation of bacteria from the gut

Experiments were performed in mice to determine whether endotoxin could cause bacteria normally colonizing the gut to spread systemically, a process termed bacterial translocation. Endotoxin given intraperitoneally promoted bacterial translocation in a dose-dependent fashion from the gut to the mesenteric lymph node (MLN). The incidence of bacterial translocation to the MLN was similar whether the endotoxin was administered intramuscularly or intraperitoneally, although the number of bacteria colonizing the MLN was greater with intraperitoneal endotoxin. The incidence and magnitude of endotoxin-induced bacterial translocation were similar between CD-1 and C3H/HeJ (endotoxin-resistant) mice, indicating that bacterial translocation is not prevented by genetic resistance to endotoxin. Thus, it appears that the gut may serve as a reservoir for bacteria causing systemic infections during endotoxemia.