多器官功能不全综合征时肠道细菌易位及通里攻下法影响的 …

肠道是全身感染的起源,细菌易位在ＭＯＤＳ的发生发展中具有重要作用。本实验以放射性同位素＾３５Ｓ档记致病Ｅ．ｃｏｌｉｓ作示踪剂,研究不同剂量酵母多糖腹腔注射所致ＭＯＤＳ时肠道细菌易位的途径和程度。并观察通里攻下中药和抗性素对细菌易位的影响。     

急性出血坏死性胰腺炎早期细菌易位规律及生长抑素的头孢噻甲羧肟对其影响

目的：探讨急性出血坏死性胰腺炎（ＡＨＮＰ）早期细菌易位规律及生长抑素（ｓｔｉｌａｍｉｎ）与头孢噻甲羧肟（Ｃｅｆｔａｚｉｄｉｍｅ）对其的影响。方法：应用去氧胆酸钠逆行胰管注射致大鼠ＡＨＮＰ模型。一、将ＳＤ大鼠随机分为模型组和对照组,１２及２４小时后采样。二、将ＳＤ大鼠模型随机分为：生理盐水治疗组,Ｓｔｉｌａｍｉｎ治疗组,Ｃｅｆｔａｚｉｄｉｍｅ治疗组,对照组同上。各组经腹腔用药,２４小时后采样,观察各组胰肝细菌学指标、小肠粘膜改变、肠组织ＭＤＡ含量及胰腺光镜病理学评分。结果：一、模型组胰肝细菌检出率及菌落计数明显高于假手术组（Ｐ＜００５）,检出菌以大肠杆菌和肠球菌为主,肠粘膜病变主要在回肠。二、肝胰菌落计数（ＣＦＵ／ｇ）：生长抑素组和抗生素组明显低于盐水组,（Ｐ＜００５）。抗生素组检出的细菌以肠球菌为主。生长抑素组肠粘膜病变较其它组明显减轻,且肠组织ＭＤＡ含量明显减少（Ｐ＜００１）,除出血外（Ｐ＜００５）胰腺病理评分较其它组未见显著差异。结论：ＡＨＮＰ早期应用抗生素和生长抑素能减轻细菌的肠道透壁易位,但不能阻止耐药菌易位。生长抑素腹腔用药能保护肠粘膜屏障。其机理与减轻氧自由基对肠道损伤有关     

多器官功能不全综合征时肠道细菌微生态学改变的实验研究

为研究多器官功能不全综合征（ＭＯＤＳ）时肠道细菌微生态的变化以及Ｇ＾－杆菌消长与肠道和血液中内毒素水平的关系,本实验选用ＳＤ大鼠,应用无菌Ｚｙｍｏｓａｎ腹腔注射制备大鼠ＭＯＤＳ模型,并对ＭＯＤＳ大鼠肠道菌群进行定量分析,对门静脉和外周静脉血中的内毒以及肠道游离内毒素含量进行定量测定。结果发现,ＭＯＤＳ状态下肠道细菌微生态发生明显变化,表现为肠杆菌和肠球菌等肠道内需氧菌的数量明显增多,双歧杆菌和乳酸     

氮离子注入对耐辐射异常球菌SOD活性的影响及其对Mn—SOD的诱导

研究了氮离子注入对耐辐射异常球菌（Ｄｅｉｎｏｃｏｃｃｕｓｒａｄｉｏｄｕｒａｎｓ）细胞内超氧化物歧化酶（ＳＯＤ）活性的影响及其对ＭｎＳＯＤ的诱导。结果表明,当２０ｋｅＶ氮离子的注入剂量低于８×１０１４ｉｏｎｓ／ｃｍ２时,Ｄ．ｒａｄｉｏｄｕｒａｎｓ中ＳＯＤ活性变化不大,当剂量在８×１０１４～６０×１０１４ｉｏｎｓ／ｃｍ２范围内时,ＳＯＤ的活性随着注入剂量的增大逐渐提高,但大于６０×１０１４ｉｏｎｓ／ｃｍ２时,则逐渐下降;加入对不同金属辅基的ＳＯＤ同工酶活性抑制剂Ｈ２Ｏ２和氯仿乙醇的研究表明,中高剂量下氮离子注入诱导的是Ｄ．ｒａｄｉｏｄｕｒａｎｓ中ＭｎＳＯＤ活性的提高,在正常生理条件及小于８×１０１４ｉｏｎｓ／ｃｍ２的剂量下,Ｄ．ｒａｄｉｏｄｕｒａｎｓ中ＳＯＤ总活性主要由ＦｅＳＯＤ构成     

大承气汤对MODS时肠道细菌微生态学影响的实验研究

目的探讨多器官功能不全综合征(MODS)大鼠肠道细菌微生态的变化及其与肠源性内毒素血症和细菌易位的关系,并观察大承气汤的影响。方法32只SD大鼠随机分成4组,对照组、模型组、大承气组和氨苄青霉素组。腹腔注射无菌酵母多糖A制备大鼠MODS模型。各组动物于造模后48 h无菌操作抽取外周静脉血和门静脉血进行内毒素含量测定;取肠系膜淋巴结进行细菌定量培养,取回肠和盲肠内容物进行肠腔内游离内毒素测定;取盲肠内容物进行肠道细菌微生态学分析。结果模型组外周血和门静脉血内毒素水平以及肠腔内游离内毒素含量均明显高于对照组(P<0.05);与对照组相比,模型组肠道菌群出现明显变化。肠球菌、肠杆菌数量明显增加,而双歧杆菌和乳酸杆菌数量出现显著下降,类杆菌数量亦出现明显下降(P<0.05)。模型组厌氧菌总数明显下降而需氧菌总数明显增加,同时厌氧菌总数/需氧菌总数的比值和B/E比值呈相应下降,发生倒置(P<0.05);正常对照组未发现肠道细菌向肠系膜淋巴结的易位,而模型组细菌易位阳性率是83.33%(P<0.05)。与模型组相比,大承气汤组上述各指标均出现明显变化(P<0.05);抗生素组作用不明显(P>0.05)。结论MODS时大鼠肠道细菌微生态出现明显变化,发生肠源性内毒素血症和细菌易位。大承气汤可以调整肠道菌群,恢复肠道微生态平衡,增加机体定植抗力,防治细菌易位和内毒素血症。     

兔迷走复合区内微量注射TRH对奥迪氏括约肌肌电的影响及传出途径分析

目的和方法：本工作旨在研究免迷走复合区（ＤＶＣ）内ＴＲＨ对奥迪氏括约肌（ＳＯ）肌电的调节作用及外周途径。结果：（１）ＤＶＣ内注射ＴＲＨ（０．８ｎｍｏｌ,１μｌ）后,慢波电位（ＳＷ）频率不变,但锋电位频率（ＦＳＰＳＯ）及幅度（ＡＳＰＳＯ）、锋电位发生率（ＩＳＰ）明显增加．（２）ＤＶＣ内分别注射不同剂量ＴＲＨ（０．１３,０．２５,０．５０,０．８０,１．３０ｎｍｏｌ,１μｌ）后,各剂量ＴＲＨ均能引起ＦＳＰＳＯ增加。随注射剂量的增加,ＳＯ反应强度和持续时间均增加,呈现明显的剂量反应关系。（３）ＤＶＣ内注射ＴＲＨ兴奋ＦＳＰＳＯ的效应可被静脉注射阿托品（０．２ｍｇ／ｋｇ）或迷走神经切断完全阻断,但不能被静脉注射酚妥拉明（１．５ｍｇ／ｋｇ）、心得安（１．５ｍｇ／ｋｇ）或脊髓切断术所阻断。结论：ＤＶＣ内ＴＲＨ可能对ＳＯ肌电有重要的调节作用,这种作用是通过迷走神经及外周Ｍ受体介导。     

氮离子注入对耐辐射异常球菌SOD活性的影响及其对Mn-SOD的诱导

研究了氮离子注入对耐辐射异常球菌（Ｄｅｉｎｏｃｏｃｃｕｓｒａｄｉｏｄｕｒａｎｓ）细胞内超氧化物歧化酶（ＳＯＤ）活性的影响及其对ＭｎＳＯＤ的诱导。结果表明,当２０ｋｅＶ氮离子的注入剂量低于８×１０１４ｉｏｎｓ／ｃｍ２时,Ｄ．Ｒａｄｉｏｄｕｒａｎｓ中ＳＯＤ活性变化不大,当剂量在８×１０１４～６０×１０１４ｉｏｎｓ／ｃｍ２范围内时,ＳＯＤ的活性随着注入剂量的增大逐渐提高,但大于６０×１０１４ｉｏｎｓ／ｃｍ２时,则逐渐下降;加入对不同金属辅基的ＳＯＤ同工酶活性抑制剂Ｈ２Ｏ２和氯仿乙醇的研究表明,中高剂量下氮离子注入诱导的是Ｄ．Ｒａｄｉｏｄｕｒａｎｓ中ＭｎＳＯＤ活性的提高,在正常生理条件及小于８×１０１４ｉｏｎｓ／ｃｍ２的剂量下,Ｄ．Ｒａｄｉｏｄｕｒａｎｓ中ＳＯＤ总活性主要由ＦｅＳＯＤ构成     

四君子汤保护骨损伤后小鼠肠道细菌易位及促进骨修复的研究

目的 观察四君子汤对骨损伤后小鼠免疫功能和细菌易位的影响,探讨中药在提高免疫力及预防感染方面的作用.方法 通过制备小鼠股骨骨损伤模型,骨损伤后在腹腔注射抗生素的同时辅以四君子汤,观察四君子汤对小鼠吞噬细胞功能的影响和细菌易位的控制.结果 骨损伤经四君子汤治疗后肝脏细菌易位明显减少(P＜0.01);吞噬细胞功能显著增强(P＜0.01);因有效控制了感染使骨修复过程加速.结论 四君子汤能够保护骨损伤后小鼠肠道细菌易位和促进骨修复.     

强啡肽对脊髓原生型与诱生型一氧化氮合成酶活性,分布和基因表达的影响

蛛网膜下腔注射强啡肽Ａ１－１７引起剂量依赖性后肢和尾部瘫痪及甩尾甩足抑制。脊髓背角（侧）ＮＭＤＡ受体和ＮＯＳ／ＮＯ功能活性下降可能与Ｄｙｎ镇痛作用有关,脊髓腹角（）ＮＭＤＡ受体－Ｃａ＾２＋－ＮＯＳ／ＮＯ通路过度激活及ｃ－ｆｏｓ高表达可能与Ｄｙｎ致脊髓损伤作用有关。     

马齿苋多糖对肠道微生态失调小鼠血内毒素含量及肝脏细菌易位的影响

目的探讨马齿苋多糖对肠道微生态失调小鼠血内毒素含量及肝脏细菌易位的影响。方法应用盐酸林可霉素灌胃建立肠道微生态失调小鼠模型,然后用马齿苋多糖进行治疗,同时设正常对照组、阳性对照组和阴性对照组,于给药7 d后处死小鼠,进行血内毒素含量测定及细菌易位检测。结果盐酸林可霉素灌胃3 d后,小鼠肠道菌群失调、血内毒素含量增加、肝脏有肠杆菌易位。用马齿笕多糖治疗7 d后,血内毒素含量降低、肝脏肠杆菌数量减少。结论马齿笕多糖对肠道微生态失调小鼠血内毒素含量及肝脏细菌易位具有调整作用。     

党参合剂对多器官功能障碍综合征菌群失调及免疫功能的调整

目的研究党参合剂通过调整菌群失调,修复肠屏障功能,控制细菌、内毒素易位,提高机体免疫力,对多器官功能障碍大鼠肠源性感染及内毒素血症(IETM)进行防治。方法采用肠缺血再灌注的方法制造多器官功能障碍综合征(MODS)模型,分别以党参合剂、丽珠肠乐对动物进行灌胃治疗。取肠内容物、肝、脾、肠系膜淋巴结,门静脉血,分别做无菌培养,内毒素及sIgA的测定。结果各治疗组通过扶植肠道有益菌、抑制有害菌的生长繁殖并促进其排泄,保护肠黏膜屏障,明显降低了细菌易位,控制内毒素血症,改善了相关免疫指标。结论党参合剂从调整微生态失调的角度来防治MODS取得较好效果,优于丽珠肠乐。     

Effects of lactulose and lactitol on coliform bacteria and bacterial translocation in the caecum during 72-h starvation in rats

Lactulose and lactitol, non-absorbable disaccharides, prevent bacterial translocation (BT) arising from the gut. In contrast, lack of food into the gut leads to coliform bacterial overgrowth and even if it does not cause BT, can induce the risk from other stimuli for BT. In this study, we tested whether lactulose and lactitol affected populations of coliform bacteria in the caecum during starvation in Sprague-Dawley rats. Three groups of rats were starved for 72 h and given oral 2 ml undiluted lactulose (670 mg/ml), 2 ml undiluted lactitol (666 mg/ml) or 2 ml physiological saline, respectively, once a day. The caecum and mesenteric lymph nodes (MLNs) were removed for microbiological and histopathological analyses. The highest degree of coliform bacterial overgrowth, BT to MLNs and histopathological damage were observed in lactulose-treated rats, followed by the group treated with lactitol. As a result of this study, both drugs, especially lactulose augmented the proliferation and translocation tendency of coliform bacteria in the caecum during 72-h starvation in rats.     

Mesenteric lymph system constitutes the second route in gut–liver axis and transports metabolism-modulating gut microbial metabolites

The gut–liver axis denotes the intricate connection and interaction between gut microbiome and liver, in which compositional and functional shifts in gut microbiome affect host metabolism. Hepatic portal vein of the blood circulation system has been thought to be the major route for metabolite transportation in the gut–liver axis, but the existence and importance of other routes remain elusive. Here, we perform metabolome comparison in blood circulation and mesenteric lymph systems and identify significantly shifted metabolites in serum and mesentery. Using cellular assays, we find that the majority of decreased metabolites in lymph system under high-fat diet are effective in alleviating metabolic disorders, indicating a high potential of lymph system in regulating liver metabolism. Among those, a representative metabolite, L-carnitine, reduces diet-induced obesity in mice. Metabolic tracing analysis identifies that L-carnitine is independently transported by the mesenteric lymph system, serving as an example that lymph circulation comprises a second route in the gut–liver axis to modulate liver metabolism. Our study provides new insights into metabolite transportation via mesenteric lymph system in the gut–liver axis, offers an extended scope for the investigations in host-gut microbiota metabolic interactions and potentially new targets in the treatment of metabolic disorders.     

Gut lymph and lymphatics: a source of factors leading to organ injury and dysfunction

Major trauma, shock, sepsis, and other conditions can lead to the acute respiratory distress syndrome (ARDS), which may progress to the highly lethal multiple organ dysfunction syndrome (MODS). Although a number of therapeutic strategies have been initiated, their success has been limited largely due to an incomplete understanding of the biology of MODS. However, recent studies indicate that the intestinal lymphatics serve as the primary route for nonbacterial, tissue injurious gut-derived factors, which can induce acute ARDS and MODS. The gut lymph hypothesis of ARDS and MODS thus helps clarify several important issues. First, because the lung is the first organ exposed to mesenteric lymph and not the liver (i.e., mesenteric lymph enters the subclavian vein via the thoracic duct, which, in turn, empties directly into the heart and lungs), it would explain the clinical observation that the lung is generally the first organ to fail. Second, this hypothesis provides new pathophysiologic information, thereby providing a basis for novel therapies. Finally, by studying the composition of lymph, MODS-inducing factors can be isolated and identified.     

肠道菌群及内毒素在多器官功能不全综合征时的变化

目的　探讨肠道菌群及内毒素在多器官功能不全综合征( MODS)时的变化。方法　取SD大鼠,腹腔注射无菌酵母多糖A制备MODS模型,检测大鼠肠道菌群、外周血和门静脉血中的内毒素以及肠道游离内毒素含量,并进行定量分析。结果　模型组大鼠肠道专性厌氧菌的数量明显减少,革兰阴性杆菌和双歧杆菌的比例倒置,内毒素含量明显增加,与对照组比差异有显著性( P<0 .0 5 )。结论　MODS时肠道细菌微生态发生明显改变,肠道内毒素池与肠道革兰阴性杆菌的变化密切相关     

Gut-derived endotoxin translocation is the main aggravating mechanism of acute severe pancreatitis

Severe acute pancreatitis (SAP) is a serious systemic disease. It exacerbates when complicated with multiple organ dysfunction syndrome or failure (MODS or MOF). However, the aggravating mechanism of SAP is still unknown up to now. Study showed that maintaining integrity of intestinal mucosal barrier function by given effective antibiotics, selective digestive decontamination (SDD) and enteral nutrition therapy to the patients with SAP could significantly reduce infection of pancreatic necrotic tissue and improve the patient's outcome. Combining the findings of gut-derived bacteria in animals' pancreas, liver, spleen, mesenteric lymph nodes with increasing concentration of inflammatory cytokines and endotoxin in plasma with SAP, we hypothesize that gut-derived endotoxin translocation is the main aggravating mechanism of SAP. The hypothesis holds potential as a target for therapeutic intervention.     

Intestinal Translocation of Clinical Isolates of Vancomycin-Resistant Enterococcus faecalis and ESBL-Producing Escherichia coli in a Rat Model of Bacterial Colonization and Liver Ischemia/Reperfusion Injury

The objectives of this study were to develop a rat model of gastrointestinal colonization with vancomycin-resistant Enterococcus faecalis (VRE) and extended-spectrum beta-lactamase (ESBL)-producing E. coli and to evaluate intestinal translocation to blood and tissues after total and partial hepatic ischemia. Methods - We developed a model of rat colonization with VRE and ESBL-E coli. Then we studied four groups of colonized rats: Group I (with hepatic pedicle occlusion causing complete liver ischemia and intestinal stasis); Group II (with partial liver ischemia without intestinal stasis); Group III (surgical manipulation without hepatic ischemia or intestinal stasis); Group IV (anesthetized without surgical manipulation). After sacrifice, portal and systemic blood, large intestine, small intestine, spleen, liver, lungs, and cervical and mesenteric lymph nodes were cultured. Endotoxin concentrations in portal and systemic blood were determined. Results – The best inocula were: VRE: 2.4×10¹⁰ cfu and ESBL-E. coli: 1.12×10¹⁰ cfu. The best results occurred 24 hours after inoculation and antibiotic doses of 750 µg/mL of water for vancomycin and 2.1 mg/mL for ceftriaxone. There was a significantly higher proportion of positive cultures for ESBL-E. coli in the lungs in Groups I, II and III when compared with Group IV (67%; 60%; 75% and 13%, respectively; p:0.04). VRE growth was more frequent in mesenteric lymph nodes for Groups I (67%) and III (38%) than for Groups II (13%) and IV (none) (p:0.002). LPS was significantly higher in systemic blood of Group I (9.761±13.804 EU/mL−p:0.01). No differences for endotoxin occurred in portal blood. Conclusion –We developed a model of rats colonized with resistant bacteria useful to study intestinal translocation. Translocation occurred in surgical procedures with and without hepatic ischemia-reperfusion and probably occurred via the bloodstream. Translocation was probably lymphatic in the ischemia-reperfusion groups. Systemic blood endotoxin levels were higher in the group with complete hepatic ischemia.     

Effect of tryptophan administration on circulating melatonin levels in chicks and rats: evidence for stimulation of melatonin synthesis and release in the gastrointestinal tract.

The administration of L-tryptophan (Trp, 150-300 mg/kg) to rats and chicks causes a rapid and dose-dependent elevation of circulating melatonin. The elevation of serum melatonin was greater after oral compared to the intraperitoneal route of administration of the same dose of Trp (150 mg/kg). The Trp-induced increase of circulating melatonin was unaffected by prior pinealectomy but was almost abolished by a partial ligature of the portal vein. The Trp-induced increase of melatonin in the portal blood preceded that in the systemic circulation. The gut contains considerable amounts of melatonin and the Trp-induced elevation of melatonin was greater in the duodenum compared to the pineal or the blood. The enterochromaffin cells of the gastrointestinal tract appear to be the major source of the Trp-induced increment of circulating melatonin. The possibility is discussed that the sedating, sleep inducing effects of Trp are mediated by the Trp-induced elevation of circulating melatonin.