重症急性胰腺炎时细胞因子与肠源性细菌和内毒素移位的实验研究

目的 探讨重症急性胰腺炎(SAP)时血浆细胞因子与肠道屏障损害后肠源性细笛和内毒素移位的关系。方法 将SD大鼠(清洁级)72只随机分为假手术组(n=36)和SAP组(n=36)。采用胰管内逆行注射4％牛磺胆酸钠溶液的方法制作SAP模型。观察胰腺和回肠的病理改变，动态测定血浆TNF-a、IL-6、IL-10和DAO活性、LPS水平以及腹腔脏器细菌移位率。结果 制模后血浆TNF-a、IL-6水平明显升高，48h达到高峰，IL-106h后才明显升高；血浆DAO活性早期升高，24h后明显降低；LPS水平早期即有明显升高，48h达到高峰；SAP24h脏器细笛移位率明显升高，72h达到58．3％。结论 SAP早期即有细胞因子水平的升高和肠道屏障的损害，细胞因子通过损害肠遗屏障，引起肠源性细菌和内毒素移位；同时，肠源性细菌和内毒素移位又促进细胞因子的大量释放。加重肠黏膜屏障本身的损害，遣成恶性循环，引起SIPS和MODS的发生，两者关系密切。     

烧伤后肠源性高代谢研究--高代谢及内毒素

目的 :探讨烧伤后高代谢与内毒素的关系。　方法 :观察了 4 0例严重烧伤病人 ,烧伤总面积达 (45±11.3) % ,其中深度烧伤为 (2 9.7± 10 .4 ) %。观察指标为静息能量消耗 (REE)、血浆内毒素、丙二醛 (MDA)、超氧化物歧化酶 (SOD)、肿瘤坏死因子 (TNF)、白细胞介素 8(IL 8)、高血糖素、皮质醇、血清二胺氧化酶 (DAO)及尿乳果糖 /甘露醇比值 (L/M)、尿儿茶酚胺。　结果 :①烧伤后 1～ 14天观察期间 ,REE与血浆内毒素、TNF、IL 8、高血糖素呈显著相关 (r分别为 0 .5 985、0 .92 36、0 .8381、0 .85 17,P分别为 0 .0 14 3、0 .0 0 11、0 .0 0 94、0 .0 0 73) ;血清DAO与血浆SOD呈显著负相关 (r=- 0 .7871,P =0 .0 2 0 4 ) ,尿L/M与血浆SOD、MDA亦呈显著相关 (r =- 0 .9114、0 .94 4 5 ,P=0 .0 0 16、0 .0 0 0 4 )。②复苏期后 (伤后 4～ 14天 ) ,REE与SOD呈显著负相关 (r=- 0 .7180 ,P <0 .0 5 )。　结论 :烧伤后高代谢与内毒素、TNF、IL 8、高血糖素有关 ,伤后肠道损伤与早期缺血 再灌注损伤有关 ,血内毒素增高可能与肠道损伤所致的肠道内毒素移位有关。     

肝病与肠源性内毒素血症防治

肠源性内毒素血症在患肝病时增加 ,内毒素血症引起细胞因子反应 ,尤其是肿瘤坏死因子α(ＴＮＦ α) ,后者又反过来使肝病加重。本文对内毒素导致肝损伤机理进行了初步探讨 ,在各种肝病类型中 ,慢性重型肝炎的肠源性内毒素血症发生率高达 84 %。此外 ,患乙型肝炎的孕妇有 5 7%可以检出肠源性内毒素血症 ,对妊娠可造成不良影响 ,甚至可引起流产或早产。益生菌制剂和肠道选择性去污染 ,有助于防止肝病患者发生肠源性内毒素血症。近年来 ,肠源性内毒素血症 (ｉｎｔｅｓｔｉｎａｌｏｒｉｇｉｎａｔ ｅｄｅｎｄｏｔｏｘｅｍｉａ ,ＩＥＴＭ )与肝病…     

肝硬化与肠源性内毒素血症关系的研究进展

<正>肝硬化是一种或多种原因引起的,以肝组织弥漫性纤维化、假小叶和再生结节为组织学特征的进行性慢性肝病,是我国常见疾病和主要死亡病因之一。引起肝硬化的病因很多,我国以病毒性肝炎所致的肝硬化为主,而国外以酒精性肝硬化多见。当机体发生肝硬化时,由于肠道细菌过度生长、肠道黏膜通透性增高、内毒素灭活功能减退等原因导致肠道的细菌及其相关产物(如内毒素)突破肠道屏障,从肠道转移到肠系膜淋巴结及其他肠外器官,从而     

肠毒清颗粒治疗慢性重型乙型肝炎肠源性内毒素血症52例疗效观察

目的:研究临床上应用肠毒清颗粒治疗慢性乙肝肠源性内毒素血症的效果如何.方法:选择2008年7月到2010年7月我院52例慢性重型乙肝肠源性内毒素血症病人,分成对照组和治疗组两组,每组各26例.对照组患者实施西医综合治疗,治疗组患者在西医治疗的基础上加用中医口服肠毒清颗粒治疗,两组患者均以四周时间为一个治疗疗程.对两组患者治疗前、后的临床症状及临床疗效改善情况进行仔细观察.结果:治疗组总有效率明显高于对照组,病死率明显低于对照组.结论:肠毒颗粒能有效改善慢性重型乙肝肠源性内毒素血症病人的临床症状,临床上值得推广应用.     

肠源性内毒素血症在拟阿尔茨海默病模型脑组织凋亡中的作用初探

[目的]通过检测拟阿尔茨海默病(Alzheimer s disease,AD)模型大鼠血浆中内毒素(Lipopolysaccharide,LPS)水平及脑组织细胞凋亡(apoptosis,programmed cell death,PCD)水平,揭示(Intestinal endotoxemia,IETM)在拟AD模型大鼠中对凋亡的影响,从而为进一步揭示IETM.在AD发生发展过程中的作用奠定基础.[方法]选用Wistar大鼠,腹腔注射D-半乳糖和AICl3连续90 d,制备拟AD模型.Morris水迷宫检测大鼠学习记忆水平,流式细胞仪和末端脱氧核糖转移酶介导的生物素化脱氧尿嘧啶缺刻标记技术(TdT-mediated dUTP-biotin nick end labeling,TUNEL)检测脑细胞凋亡,鲎试剂法检测大鼠血浆LPS水平.[结果]拟AD模型组大鼠逃避潜伏期(25±9)s,明显长于空白对照组(12±5)S(P＜0.01);模型大鼠体内LPS、TNF-α、脑细胞凋亡率(PD)及TUNEL染色阳性细胞数均明显高于对照组(P＜0.01).[结论]拟AD模型大鼠体内LPS、TNF-α水平及脑细胞凋亡率明显升高,IETM可能是拟AD大鼠模型脑细胞凋亡的原因之一.     

慢性乙型肝炎患者肠源性内毒素血症中免疫调节细胞因子表达变化的研究

目的：研究慢性乙型肝炎（chronic hepatitis B,CHB）患者肠源性内毒素血症（intestinal endotoxemia, IETM）中与调节性T细胞（regulatory T cells,Treg）、Th17细胞相关免疫调节细胞因子的表达变化。方法：应用ELISA法分别对80例CHB患者和20例健康对照者的血浆IL-10、TGF-β、IL-6、IL-17、IL-23及内毒素水平进行检测。根据测定的内毒素水平,将CHB患者分为内毒素阳性组和内毒素阴性组。结果：CHB患者血浆IL-10、TGF-β、IL-6、IL-17、IL-23水平均明显高于健康对照组（Z值分别为5.265、6.859、6.894、5.028、6.877,均P〈0.01）。内毒素阳性组患者明显高于内毒素阴性组和健康对照组（H值分别为45.833、48.423、48.984、75.184、75.814,均P〈0.01）。结论：CHB患者IETM时血浆中与Treg、Th17细胞相关细胞因子水平进一步增高。     

阿尔茨海默病模型大鼠肠源性内毒素血症发生机制的研究

目的研究D-半乳糖和三氯化铝(AlCl3)联合制备的阿尔茨海默病(Alzheimer′s disease,AD)大鼠模型中肠源性内毒素血症(intestinal endotoxemia,IETM)发生的机制。方法选用雄性Wistar大鼠,腹腔注射D-半乳糖和AlCl3连续90 d制备AD大鼠模型。给药结束后,通过生化检测、免疫组化检测AD模型大鼠血浆内毒素(lipopolysaccharide,LPS)、肿瘤坏死因子-α(TNF-α),白细胞介素-1β(IL-1β)的水平及肝脏枯否细胞(Kupffer cell,KC)功能、肠黏膜屏障功能。结果AD模型组大鼠血浆LPS、TNF-α及IL-1β水平明显高于对照组(P0.05),肝脏KC吞噬及肠粘膜屏障功能均下降。结论在D-半乳糖和AlCl3联合制备AD大鼠模型中由于肝脏KC吞噬及肠粘膜屏障功能的下降使得LPS入血增多,发生IETM。     

肠源性内毒素血症在代谢综合征相关的动脉粥样硬化所致的心肌损伤研究

目的探讨肠源性内毒素血症在代谢综合征相关的动脉粥样硬化所致的心脏损伤的发生机制。方法 SD大鼠64只随机分为对照组和模型组,各32只;每组再随机分为3月、6月、9月、12月4个时段进行实验观察,每时段8只。对照组喂饲基础饲料,模型组喂饲高糖高脂饲料。应用放免法及酶联免疫吸附实验测定外周血内毒素及相关的炎症介质肿瘤坏死因子α(TNF-α)、C反应蛋白(CRP)、巨噬细胞趋化蛋白-1(MCP-1)的表达以及甘油三酯、总胆固醇、游离脂肪酸、高密度脂蛋白胆固醇、低密度脂蛋白胆固醇、空腹血糖、空腹胰岛素的表达;并观察主动脉及心脏病理形态学变化;免疫组织化学染色CD68及Tunnel观察巨噬细胞在心肌的浸润及心肌凋亡情况;苏丹IV特殊染色观察脂质在心肌细胞内和心肌肌束间的异位沉积情况。结果模型组大鼠从第3月即发生了内毒素血症和胰岛素抵抗;同时出现了中心性肥胖、脂代谢紊乱、高血糖症及高胰岛素血症等代谢综合征,病理形态学显示模型组随鼠龄增加,主动脉发生脂质异位沉积及典型的动脉粥样斑块的形成;心肌细胞内及心肌肌束间于第6个月出现显著的脂质沉积,在第9～12月加重至严重程度,心肌细胞凋亡于6月组明显发生,第9～12月组发生较广泛凋亡。结论高糖高脂膳食可诱导肠源性内毒素血症和胰岛素抵抗的发生,可能在代谢综合征及其相关的疾病如动脉粥样硬化及其相关的心肌损伤中起重要作用。     

裸燕麦β-葡聚糖调节血脂及改善肠源性内毒素血症作用的实验研究

目的探究裸燕麦β-葡聚糖调节血脂过程中对肠道菌群的影响。方法用高脂饲料喂养金黄地鼠建立血脂异常模型,造模后将血脂异常鼠随机分为2组并分别以普通饲料、裸燕麦β-葡聚糖干预饲料饲养建立模型组(M)、干预组(OM),另设正常组(N)、预防组(OMN),以上各组动物每组12只,实验期90d。在干预初期、中期及末期检测各组血脂4项,同时进行粪便肠杆菌和双歧杆菌平板培养,末期测血清脂多糖(LPS)和炎症因子肿瘤坏死因子(TNF-α)、白介素-6(IL-6)。结果干预初期,OMN组的血清总胆固醇(TC)、总甘油三酯(TG)与低密度脂蛋白胆固醇(LDL-C)水平比N组低(P0.05),OM组与M组血脂水平一致,干预末期,OM组血清TC、TG、LDL-C水平分别达到3.64mmol/L、2.52mmol/L、0.69mmol/L,相比造模时均显著下降(P0.01),其中TC与LDL-C水平显著低于M组(P0.01),此外,OM组肠杆菌与双歧杆菌比值在干预45d后即显著下降(P0.01),并在90d时显著低于M组(P0.01),同时,干预结束时OM组血清LPS水平为13.67μg/L,显著低于M组(P0.01),OM组血清炎症因子IL-6为44.80ng/L、TNF-α为376.95ng/L,显著低于M组(P0.01)。结论对血脂异常的个体,裸燕麦β-葡聚糖在有效调节血脂的同时可改善肠道肠杆菌与双歧杆菌比例并纠正菌群紊乱带来的肠源性内毒素血症,降低机体炎症水平。     

谷氨酰胺对猪急性重症胰腺炎后肠源性细菌/内毒素易位的影响

目的：观察静脉内滴注谷酰胺（Ｇｌｎ）对急性重症胰腺炎（ＡＳＰ）后肠源性细菌／内毒素易位的保护作用。方法：选健康长白种猪２１头，体重１６－２２ｋｇ，雌雄不限，随机分为四组，１组：假手术对照组（ｎ＝５）；Ⅱ组：ＡＳＰ对照组ｎ＝５）；Ⅲ组：ＡＳＰ＋甘氨酸（Ｇｌｙ）组（ｎ＝５）；Ⅳ组：ＡＳＰ＋Ｇｌｎ组（ｎ＝６）。在麻醉状态下，进腹向胰管内注入５％牛磺胆酸钠混合液１ｍｌ／ｋｇ（内含８０００－１００００ＢＡＥ     

Relationship between fasting urinary nitrogen loss and obligatory nitrogen loss in rats

The relationship between obligatory nitrogen loss (ONL) and fasting urinary nitrogen loss (FUNL) was investigated in a longitudinal study in rats aged 30–430 days. Although both measurements increased with body size, when scaled allometrically they showed a decline. The rates of decline were parallel, such that at all ages the relationship between the two was FUNL=1.5 ONL. At any age inter-individual variability in this ratio was relatively small, the coefficient of variation being <7%. We propose that FUNL may be used as a proxy for the measurement of ONL and hence protein requirements. The reported relationship may also provide a theoretical basis for the well known but enigmatic relationship between BMR and ONL.     

氯胺酮对内毒素致急性肺损伤细胞因子表达的影响

目的观察氯胺酮对内毒素致大鼠肺组织细胞因子表达的影响,探讨氯胺酮抑制炎性反应的机制。方法成年大鼠20只随机分为四组(每组5只),对照组(C组)、内毒素组(L组)、内毒素+氯胺酮20μg/kg·min(L+K20组)、内毒素+氯胺酮40μg/kg·min(L+K40组)。在注射内毒素4h后处死动物开胸取标本,用分光光度法测定诱生型一氧化氮合成酶(iNOS)、丙二醛(MDA)、NO-2/NO-3浓度。结果L组肺组织的因子的表达明显增高,氯胺酮预处理组肺组织iNOS、MDA、NO-2/NO-3浓度较L组明显下降,且随着氯胺酮剂量的增加而抑制效应增加。结论氯胺酮能明显抑制内毒素诱导大鼠肺细胞因子的表达,对内毒素致肺损伤有保护作用。     

Age-related effects of fasting on ketone body production during lipolysis in rats

Objective

The age-related effects of fasting on lipolysis, the production of ketone bodies, and plasma insulin levels were studied in male 3-, 8-, and 32-week-old Sprague–Dawley rats.

Methods

The rats were divided into fasting and control groups. The 3-, 8- and 32-week-old rats tolerated fasting for 2, 5, and 12 days, respectively.

Results

Fasting markedly reduced the weights of perirenal and periepididymal white adipose tissues in rats in the three age groups. The mean rates of reduction in both these adipose tissue weights during fasting periods were higher in the order of 3 > 8 > 32-week-old rats. Fasting transiently increased plasma free fatty acid (FFA), total ketone body, β-hydroxybutyrate, and acetoacetate concentrations in the rats in the three age groups. However, plasma FFA, total ketone body, β-hydroxybutyrate, and acetoacetate concentrations in the 3-week-old rats reached maximal peak within 2 days after the onset of fasting, although these concentrations in the 8- and 32-week-old rats took more than 2 days to reach the maximal peak. By contrast, the augmentation of plasma FFA, total ketone body, β-hydroxybutyrate, and acetoacetate concentrations in the rats in the three age groups had declined at the end of each experimental period. Thus, the capacity for fat mobilization was associated with tolerance to fasting. Plasma insulin concentrations in the rats in the three age groups were dramatically reduced during fasting periods, although basal levels of insulin were higher in the order of 32 > 8 > 3 week-old rats.

Conclusion

These results suggest that differences in fat metabolism patterns among rats in the three age groups during prolonged fasting were partly reflected the metabolic turnover rates, plasma insulin levels, and amounts of fat storage.     

内毒素耐受对D-GalN/LPS致大鼠肝损伤保护

目的 研究内毒素耐受(endotoxin tolerance,ET)对大鼠接受D-胺基半乳糖(D-GalN)/脂多糖(LPS)刺激后肝组织超微结构改变及血清细胞因子变化的影响.方法 雄性SD大鼠先以0.1mg/kg LPS腹腔注射,每日1次,连续5次,于第5次注射24h后再腹腔注射D-GalN 800 mg/kg和LPS 8μg/只,注射D-GalN/LPS 24 h后留取大鼠血及肝脏标本.苏木素-伊红染色及透射电镜下观察肝组织病理及超微结构变化;采用鲎试剂基质显色法测定血清内毒素水平.ELISA法检测肿瘤坏死因子(TNF-α)、白细胞介素-6(IL-6)水平.结果 ET组大鼠血清丙氨酸氨基转移酶(ALT)、天门冬氨酸氨基转移酶(AST)、总胆红素(TBiL)水平均明显低于急性肝衰竭(ALF)组(P＜0.01),且ET组大鼠肝组织病理改变及超微结构变化明显轻于ALF组;同时,ET组大鼠血清内毒素、TNF-α、IL-6水平亦明显低于ALF组(P＜0.01).结论 内毒素耐受时,大剂量的D-GaIN和LPS腹腔注射可减轻肝组织损害,内毒素、TNF-α、IL-6释放减少.提示内毒素耐受可能有助于防治急性肝功能衰竭.     

空腹血糖受损的中老年人血糖变化及转归的影响因素分析

[目的] 了解空腹血糖受损（IFG）的中老年人空腹血糖变化及转归情况,并分析其影响因素。[方法] 采用多阶段随机抽样方法,在上海市闸北区随机抽取2个街道,再按随机抽样方法确定居委会和楼组。选择年龄 ≥ 40岁、空腹血糖（FPG）6.1~6.9 mmol/L的常住人口进入本次研究,共203人。对该部分人群于2011-2012年间2次清晨空腹采静脉血样,检测FPG、总胆固醇（TC）、三酰甘油（TG）、高密度脂蛋白（HDL-C）、低密度脂蛋白（LDL）等生化指标,测量身高、体重、腰围、臀围,并于2012年通过问卷调查了解其生活方式及对糖尿病的认知水平。[结果] 对IFG人群连续观测2年,FPG总体水平有所上升,差异有统计学意义。FPG₁、FPG₂分别有37.44%、30.05%的居民升高到7.0 mmol/L以上,同时有38.42%、33.50%的居民FPG下降到6.1 mmol/L以下。被确诊为糖尿病者占9.85%。多因素分析发现BMI为IFG人群FPG升高的危险因素。[结论] 40岁以上IFG人群FPG水平2年内随时间总体有所升高。BMI是IFG人群FPG水平的影响因素。     

子宫内膜中细菌内毒素与体外受精-胚胎移植

近年来子宫内膜内毒素与体外受精-胚胎移植的关系逐渐引起学术界的重视,有不少学者开始着力于这方面的研究,该文针对迄今为止仍不明确的如子宫内膜内毒素是否降低体外受精-胚胎移植妊娠率、及其影响体外受精-胚胎移植的可能机制、目前仍存在的和今后有待解决的问题等加以综述.     

Modulating effects of the feeding route on stress response and endotoxin translocation in severely stressed patients receiving thoracic esophagectomy

Experimental studies have demonstrated that the route of nutritional supply impacts the systemic metabolic responses after surgical injury. Intestinal mucosal atrophy, as induced by total parenteral nutrition (TPN) or prolonged bowel rest, has been reported to enhance bowel endotoxin translocation. The operative procedure for thoracic esophageal cancer, including thoracotomy, laparotomy, and three-field lymph-node dissection, is a particularly stressful surgery that requires long-term aggressive nutritional support and often results in the postoperative hypermetabolic state, leading to perturbation of postoperative immune function. Interleukin-6 (IL-6) plays an important role in host inflammatory responses, whereas IL-10 is linked to suppression of cellular immunity. The aim of this study was to investigate how the antecedent nutritional routes influence systemic IL-6 and IL-10 responses and endotoxin translocation after an operation for thoracic esophageal cancer. Twenty-nine patients who underwent esophagectomy with three-field lymphadenectomy were investigated. They were assigned to groups receiving either TPN (n = 18) or enteral nutrition (EN; n = 11) providing 35 kcal x kg(-1) x d(-1) of energy and approximately 1.2-1.5 g x kg(-1) x d(-1) of amino acids. These nutritional supports were conducted from 1 wk before the operation to 14 d after the operation. Serum IL-6, IL-10, and endotoxin concentration were measured before and during the operation and at 2 h and 1, 3, and 7 d after the operation. IL-6 in sera was significantly higher after the operation in both groups. In the EN group, however, significantly less IL-6 production was observed on the third and seventh postoperative days when compared with those patients in the TPN group. Similarly, serum IL-10 concentration in the TPN group showed a significantly higher level than that in the EN group. Serum IL-6 showed a significant positive correlation with IL-10 at 2 h and at 7 d after the operation, suggesting that the reduced inflammatory responses were related to the inhibition of the development of postoperative immunosuppression. Endotoxin concentration in sera was significantly lower in the EN group after the operation than in the TPN group. Perioperative EN provides better regulation of inflammatory cytokine responses and may contribute less to immunosuppression after major surgery than parenteral nutrition. The attenuated production of endotoxin induced by EN may play an important role in these phenomena.