精氨酸增强全肠外营养对急性胰腺炎大鼠肠粘膜屏障的影响

目的：探讨精氨酸增强精氨酸增强ＴＰＮ对急性胰腺炎（ＡＰ）大鼠肠粘膜屏障的影响。方法：雄性ＳＤ大鼠６４只，随机分成：①对照组（ｎ＝１６）；②ＡＰ组（ｎ＝１６）；③ＡＰ＋ＴＰＮ组（ＴＰＮｓ组ｎ＝１６）；④ＡＰ＋ＴＰＮ＋精氨酸组（ＴＰＮａ组ｎ＝１６）。分别于建立急性胰腺炎模型后第１及第５天剖杀每组８只大鼠取材，检测肠粘膜一氧化氮（ＮＯ）、丙二醛、蛋白质含量、肠系膜淋巴结及门静脉血细菌移位率。结果：与对照组比较，术后１天及５天时，ＡＰ组肠粘膜丙二醛焦点量及肠系膜淋巴结细菌移位率显著升高；５天时蛋白质含量显著降低，而门静脉血细菌移位率明显升高。与ＴＰＮｓ组比较，ＴＰＮａ组１天时肠粘膜ＮＯ含量即明显升高；肠系膜淋巴结细胞移位率显著降低；５天时肠粘膜ＮＯ与蛋白质含量均显著升高；丙二醛含量显著降低。结论：急性胰腺炎可引起肠粘膜     

生态免疫肠内营养对重症胰腺炎大鼠肠屏障功能和胰腺炎症的影响

目的评估生态免疫肠内营养对重症胰腺炎（SAP）大鼠肠屏障功能和胰腺的影响。方法64只SPF大鼠随机分为对照组、SAP组、SAP普通肠内营养组（EEN组）和SAP生态免疫肠内营养组（EIN组）,分别于造模后第4天和第7天检测各组大鼠的多脏器细菌易位情况、血浆内毒素水平、肠黏膜通透性,并进行胰腺病理评分和回肠末端病理检查等。结果SAP组、EEN组和EIN组大鼠的总细菌易位率明显高于对照组（P〈0．05）,EEN组和EIN组明显低于SAP组（P〈0．05）,EIN组明显低于EEN组（P〈0．05）。SAP组、EEN组和EIN组大鼠的血浆内毒素水平和肠系膜上静脉血FD．40浓度均明显高于对照组（P〈0．01）,EEN组和EIN组均明显低于SAP组（P〈0．01）,EIN组的血内毒素水平亦低于EEN组（P〈0．05）。SAP组、EEN组和EIN组大鼠病理各单项及总评分均明显高于对照组（P〈0．01）;EEN和EIN组则明显低于SAP组（P〈0．01）;EIN组的各单项评分与EEN组差异无统计学意义（P〉0．05）,但总评分明显低于EEN组（P〈0．05）。EIN组大鼠肠黏膜较其他组明显增厚,绒毛茂盛。结论早期肠内营养对SAP大鼠肠屏障和胰腺具有保护作用,其中生态免疫肠内营养较普通肠内营养效果更佳。     

谷氨酰胺对大鼠放射性肠粘膜损伤的保护作用

目的 观察谷氨酰胺对放射性肠粘膜损伤的保护作用。方法 将30只大鼠随机分为正常对照组(A组)、照射对照组(B组)和谷氨酰胺保护组(C组)。大鼠全腹照射1 000 cGy。C组自照射前1 d开始灌服谷氨酰胺。4d后处死大鼠,检查肠道细菌移位情况、血中内毒素水平及小肠粘膜病理形态学改变。结果 A组无细菌移位,B组细菌移位最为明显,C组细菌移位远不及B组明显;A组内毒素含量极低,B组内毒素含量明显升高,C组内毒素含量明显低于B组;A组肠粘膜正常,B组肠粘膜绒毛水肿,炎性细胞浸润,部分上皮细胞脱落,C组绒毛轻度水肿,未见明显细胞脱落。结论 全腹照射能明显损伤小肠粘膜,引起细菌移位和内毒素血症,谷氨酰胺能明显减轻射线对小肠粘膜的损伤。     

肠内营养中应用谷氨酰胺对重症急性胰腺炎大鼠继发感染的影响

目的探讨早期肠内营养中应用谷氨酰胺（Gln）对重症急性胰腺炎（SAP）大鼠继发感染的影响。方法雄性SD大鼠95只，随机分成模型1天组、对照组、SAP＋肠外营养（PN）组、SAP＋肠内营养（EN）组、SAP＋EN＋Gln组，除模型1天组外，各组又分为4天喂养组和7天喂养组。分别在第4、7天检测各组各项指标，主要包括细菌移位、血浆内毒素、二胺氧化酶、肠转运功能。结果肠系膜淋巴结和肝培养出的细菌多为革兰氏阴性杆菌，以大肠杆菌为主，SAP＋EN、SAP＋EN＋Gln组显著低于SAP＋PN组（P〈0．01），SAP＋EN＋Gln组低于SAP＋EN组（P〈0．05）。各SAP组血浆内毒素水平显著高于对照组，以SAP＋PN组最高，SAP＋EN、SAP＋EN＋Gln组显著低于SAP＋PN组（P〈0．01），SAP＋EN组高于SAP＋EN＋Gln组（P〈0．05）。SAP＋PN7天组明显高于4天组（P〈0．05）。各SAP组发病4天后血浆DAO活性明显下降（P〈0．01）；7天后SAP＋EN＋Gln组回升和对照组无差异，其余各SAP组继续下降，以SAP＋PN组为甚（P〈0．01）。各SAP组的肠转运系数显著降低（P〈0．05，P〈0．01）；SAP＋EN、SAP＋EN＋Gln组显著高于SAP＋PN组（P〈0.05，P〈0．01）；SAP＋EN＋Gln和SAP＋EN组之间差异无显著性。结论肠内营养中应用谷氨酰胺能更有效地降低SAP大鼠肠道细菌移位，从而减少胰腺继发感染的发生。     

谷氨酰胺对急性重症胰腺炎大鼠胰腺继发感染的影响

目的 探讨谷氨酰胺能否减少急性重症胰腺炎（SAP）大鼠胰腺继发感染的发生，方法 SD大鼠48只，随机分成6组（n=8)。A组：假手术 肠外营养支持（PN）1d;B组：SAP PN1d；C组：SAP 谷氨酰胺（Gln)1d；D组：假手术 PN7d；E组；SAP PN7d；F组：SAP Gln7d。观察各组细菌移位情况及胰腺继发感染情况。结果 各脏器培养出的细菌多为肠道常驻菌，F组大鼠肠系膜淋巴结（MLN）及胰腺的细菌培养阳性率明显低于E组。结论 谷氨酰胺能减少急性重症胰腺炎大鼠肠道细菌移位。从而减少胰腺继发感染的发生。     

要素膳中添加肠道营养成分保护应激大鼠的肠粘膜屏障

利用应激大鼠模型，在要素膳（ED）中添加不同营养成分，观察对肠粘膜屏障的保护作用。分别在5组大鼠中，用标准ED或添加寡糖、鱼油、磨芋或果胶的ED行肠内营养3天后，造成烫伤应激模型，观察门静脉血（PVB）细菌培养、肠系膜淋巴结（MLN）细菌培养、血浆微量内毒素（LPS）、肠粘膜DNA含量以及肠粘膜形态学等指标变化。结果显示：添加鱼油、磨芋或果胶的ED能降低PVB和MLN的细菌移位率，降低LPS水平（P＜0、05），防止肠粘膜DNA的丢失（P＜005），改善肠粘膜的形态学损害，而添加寡糖的效果不明显，这种添加物的保护作用对创伤和围手术期的临床营养支持有一定参考价值。     

复合乳酸菌对重症急性胰腺炎大鼠细胞因子平衡的影响

目的构建大鼠重症急性胰腺炎(SAP)模型,探讨复合乳酸菌对SAP大鼠细胞因子和肠道免疫屏障的影响。方法96只Sprague-Dawley大鼠,体重(200±10)g,随机分为12组(n=8),包括假手术早期肠内营养治疗(Sham-EEN)4天、7天组、早期肠内营养治疗(EEN)4天、7天组、早期肠内营养加复合乳酸菌治疗(EEN Lac)4天、7天组;假手术肠外营养治疗(Sham-PN)4天、7天组、肠外营养治疗(PN)4天、7天组、肠外营养加复合乳酸菌治疗(PN Lac)4天、7天组。采用胰腺被膜下均匀注射3.8%牛磺胆酸钠1ml的方法建立大鼠SAP模型。分别于第4和7天取材,检测血清肿瘤坏死因子-α(TNF-α)和白介素-10(IL-10)的水平,评价IL-10/TNF-α的平衡状态;并检测小肠黏液SIgA含量。结果(1)血清TNF-α水平各SAP模型组均显著高于假手术组(P<0.05);PN组显著高于EEN组和EEN Lac组(P<0.05);EEN组显著高于EEN Lac组(P<0.05);PN组显著高于PN Lac组(P<0.05);各SAP模型4天组显著高于7天组(P<0.05)。(2)血清IL-10水平各SAP模型组均显著高于假手术组(P<0.05);PN组显著低于EEN组和EEN Lac组(P<0.05);PN4天组低于PN Lac组(P<0.05);各SAP模型4天组显著高于7天组(P<0.05)。(3)血清IL-10/TNF-α比值PN组显著低于EEN组、EEN Lac组(P<0.05);EEN组低于EEN Lac组(P<0.05);各SAP4天组低于7天组(P<0.01)。(4)小肠黏液SIgA含量SAP模型组除了EEN Lac7天组外,其他各组均显著低于假手术组(P<0.01);各SAP模型4天组显著低于7天组(P<0.05);EEN Lac组显著高于EEN组(P<0.05),EEN Lac和EEN组显著高于PN组(P<0.05),EEN Lac组显著高于PN Lac组(P<0.05)。结论复合乳酸菌可改善SAP大鼠促炎和抗炎细胞因子的平衡状态和肠道的免疫功能;EEN在改善SAP大鼠机体炎症状态和肠道免疫功能方面优于PN。     

谷氨酰胺对短肠综合征大鼠肝脏及结肠形态的作用

目的：观察谷氨酰胺对短肠综合征大鼠肝脏和结肠形态的影响。方法：23只雄性大鼠切除80％小肠,随机分3组：饮食组8只术后自由进食,全胃肠外营养（TPN）组8只输入TPN标准液,谷氨酰胺（Gln)组7只,输TPN＋Gln,正常大鼠8只,作为对照组。术后第7天,取门静脉血测定肝功能,肝脏和结肠进行组织学检查,结果：饮食组、正常组和Gln组血ALb明显高于TPN组,Gln组血TP明显高于TPN组,光镜下Gln组（2／7）和TPN组（3／8）肝脏标本呈脂肪变性改变,两无显差别,饮食组结肠粘膜厚度明显大于正常组,Gln组结肠粘膜厚度明显大于TPN组。结论：Gln促使结肠粘膜增生,有利于维持血TP和ALb水平,但未能减轻肝脂肪变性。     

不同营养方式对肠道缺血-再灌注大鼠肠屏障功能影响的实验研究

目的:通过建立大鼠肠道缺血-再灌注模型,以探讨不同营养物质及支持途径对肠屏障功能和细菌移位的影响. 方法:将肠道缺血-再灌注大鼠随机分成四组,每组15只,从术后第一天起行7天不同方式的营养支持.第一组为普通肠外营养(PN)组,第二组给予富含谷氨酰胺的肠外营养(G-PN)组,第三组为普通肠内营养(EN)组,第四组为免疫增强型肠内营养(IEN)组,各组营养液的热量及含氮量均相同.营养支持7天后取材,行细菌及内毒素移位、肠道形态学和肠壁淋巴细胞分布检测,用循环D-乳酸法测定肠道通透性. 结果:PN组大鼠小肠绒毛高度、粘膜厚度、隐窝深度及绒毛表面积,均显著低于其他各组(P<0.05),EN组肠粘膜形态学明显好于G-PN组(P<0.01).PN组D-乳酸水平显著高于其他各组(P<0.05).PN组血浆内毒素水平明显高于其他各组(P<0.05),EN组内毒素水平明显低于G-PN组(P<0.05),EN和IEN组无显著差异(P＝0.161).PN组细菌移位率明显高于其他各组(P<0.05),EN组与IEN组无显著差异(P＝0.682).PN组肠壁CD4 T淋巴细胞、IgA 浆细胞分布显著低于其他各组(P<0.01).IEN组CD4 T淋巴细胞、IgA 浆细胞分布显著高于其他各组(P<0.05). 结论:肠内营养在维护肠屏障功能、防止细菌移位方面优于肠外营养.谷氨酰胺对改善肠屏障功能有显著作用,但无法取代肠内营养对肠屏障功能的维护作用.免疫增强型肠内营养对改善肠道免疫功能有显著作用,但对细菌移位的防治效果并不明显.     

大豆蛋白抗辐射对肠屏障的损害

目的 确定大豆蛋白是否有保护肠屏障的作用。方法 复制SD大鼠急性放射性肠炎动物模型，给予含大豆蛋白饲料，检测脏体比、细菌移位率、血清内毒素（LPS）、光镜和扫描电镜观察肠粘膜细胞增生，测血清氨基酸、尿乳果糖／甘露醇（L／M）比值、肠内容物细菌S－IgA包被率。结果 用大豆蛋白后细菌移位率明显降低，血LPS不升高，回肠绒毛高度、肠全层厚度和粘膜厚度均高于实验对照组，肠粘膜细胞增生好于实验对照组，血清谷氨酰胺支链氨基酸含量均高于实验对照组，L／M比值、肠内容物细菌S－IgA包被率均低于实验对照组。结论 大豆蛋白有保护肠屏障的作用，可以抵抗辐射对肠屏障的损害。     

Effect of early intrajejunal nutrition on pancreatic pathological features and gut barrier function in dogs with acute pancreatitis

BACKGROUND: In patients with major trauma and burns, total enteral nutrition (TEN) significantly decreases the acute phase response and incidence of septic complications when compared with total parenteral nutrition (TPN). Traditionally, it was believed that early intrajejunal nutrition (EIN) in severe acute pancreatitis (SAP) may exacerbate the clinical pathological features, lead to recurrence of symptoms and delay complications.OBJECTIVE: To compare the effect of EIN vs TPN on the pancreatic pathological features and gut barrier function in dogs with acute pancreatitis (AP). METHODS: Fifteen dogs (surviving over 7 days, the death rate being 32%, 7/22) were divided into parenteral nutrition (PN) group (n=7) and EIN group (n=8). SAP model was induced by injecting 1 ml/kg of combined solution of 2.5% sodium taurocholate and 8000-10000 BAEE units trypsin/ml into the pancreas via the pancreatic duct. Nutrients were delivered to the EIN group by catheter via a jejunostomy feeding 24 h postoperatively. The two groups were isocaloric and isonitrogenous. Systemic blood samples were obtained before and 1, 4, 7 d following AP, and cultured by aerobic as well as anaerobic bacterial growth. Systemic plasma and portal vein endotoxin levels were quantified by the chromogenic limulus amebocyte lysate (LAL) technique. Portal vein blood and specimens of tissue from mesenteriolum and mesocolon lymph nodes, lung, pulmonary portal lymph nodes and pancreas were adopted before the experiment was finished. Aliquots of the homogenata were cultured as blood mentioned above. Serum glucose, calcium, amylase and lysosomal enzymes were determined. All dogs were injected with 50 microCi (125)I-BSA 4 h at the 7th day before being sacrificed. The (125)I-BSA indexes of the pancreas/muscle and pancreas/blood were measured, and pancreatitic pathological scores (PPSs) of the different partial pancreas were observed. The content of mucosa protein, DNA and the villi, the thickness of mucosa and the whole bowel wall of the ileum and transverse colon were measured. RESULTS: The study showed that serum glucose in the PN group was higher than in the EIN group after SAP 3 d; the levels of systemic plasma endotoxin and the magnitude of bacterial translocation to the portal and systemic blood and distant organ reduced significantly in the EIN group P<0.01. There were no differences between the two groups in the data of serum calcium, amylase and lysosomal enzymes, P>0.05; the (125)I-BSA index of pancreas/muscle and pancreas/blood, and PPS of the head, body, tail and total pancreas did not reach significant difference between the two groups, P>0.05. The contents of protein and DNA, the height of villi, the thickness of mucosa and the whole bowel wall of the ileum and transverse colon in the EIN group were higher than that in the PN group,P <0.01.CONCLUSION: Our results suggested that EIN was safe and effective to be adopted by intrajejunal delivery of nutrients in SAP dogs, did not make SAP clinical pathological features deteriorate, and decreased the occurrence rate of endotoxin and gut bacterial translocation.     

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。     

大鼠肠缺血-再灌注后营养对肠黏膜屏障功能的影响

目的:研究不同营养物质及营养支持途径对大鼠肠道缺血-再灌注时肠黏膜屏障功能的影响. 方法:将大鼠随机分为缺血-再灌注组、对照组及缺血-再灌注后各营养支持组.实验结束行肠黏膜屏障功能指标的检测. 结果:缺血-再灌注后肠黏膜发生明显损伤,普通肠外营养(PN)组D-乳酸、血浆内毒素水平、细菌移位率均显著高于其他各组(P<0.05);普通肠内营养(EN)组血浆内毒素水平明显低于谷氨酰胺肠外营养(G-PN)组(P<0.05),EN和免疫肠内营养(IEN)组细菌移位率无显著差异(P>0.05). 结论:①肠内营养在维护肠黏膜屏障功能方面优于肠外营养.②谷氨酰胺对改善肠黏膜屏障功能有显著作用,但无法取代肠内营养的作用.③免疫增强型营养与普通肠内营养相比,对细菌移位的防治效果并不大.     

Effects of Enteral Immunonutrition on the Maintenance of Gut Barrier Function and Immune Function in Pigs With Severe Acute Pancreatitis

Background: This study evaluated the effects of enteral immunonutrition (EIN) supplemented with glutamine, arginine, and probiotics on gut barrier function and immune function in pigs with severe acute pancreatitis (SAP). Methods: The model was induced by retrograde injection of 5% sodium taurocholate and trypsin via the pancreatic duct. After induction of SAP, 18 pigs were randomly divided into 3 groups, in which either parenteral nutrition (PN), control enteral nutrition (CEN), or EIN was applied for 8 days. Serum and pancreatic fluid amylase concentration was determined. Intestinal permeability (lactulose to mannitol ratio) was measured by high‐performance liquid chromatography, and plasma endotoxin was quantified by the chromogenic limulus amebocyte lysate technique. Samples of venous blood and organs were cultured using standard techniques. Pancreatitis severity and villi of ileum were scored according to histopathologic grading. Plasma T‐lymphocyte subsets were measured by flow cytometry, and immunoglobulins (Igs) were determined via enzyme‐linked immunosorbent assay. Results: There were no significant differences in serum and pancreatic fluid amylases concentrations or in pancreatitis severity between any 2 of the 3 groups. Compared with PN and CEN, EIN significantly decreased intestinal permeability, plasma endotoxin concentration, and the incidence and magnitudes of bacterial translocation, but increased ileal mucosal thickness, villous height, crypt depth, and percentage of normal intestinal villi. Significant differences were found in CD3⁺, CD4⁺ lymphocyte subsets, the ratio of CD4⁺: CD8⁺ lymphocyte subsets, and serum IgA and IgG, but not IgM, between any 2 of the 3 groups. Conclusions: EIN maintained gut barrier function and immune function in pigs with SAP.     

肠内营养在维护门静脉高压症术后患者肠道黏膜屏障功能中的作用

目的了解肠内营养在维护门静脉高压症术后患者肠道黏膜屏障功能中的作用和地位。方法40例门静脉高压症手术患者随机进入肠内(EN)或肠外营养(PN)组,术后分别接受肠内外营养,观察两种营养方式对患者内脏蛋白合成能力、肝功能及其储备、胃肠功能、内毒素水平、肠道细菌移位和乳果糖/甘露醇比值等方面的影响。结果两种营养方式均能改善患者的营养状况。EN术后并发症少,在刺激肠道蠕动,减轻内毒素水平,防止肠道菌群移位,维护肠黏膜屏障方面优于PN,且差异显著(P<0.05)。结论EN是维护此部分患者肠道黏膜免疫屏障功能稳定的有效方式。     

Effects of protein malnutrition and endotoxin on the intestinal mucosal barrier to the translocation of indigenous flora in mice

Since protein malnourished or endotoxemic patients are at increased risk of developing nosocomial infections with enteric organisms, we investigated the effects of these risk factors alone and in combination on the intestinal mucosal barrier to bacteria. Protein malnutrition resulted in severe ileal atrophy that was directly related to the length of time the mice were protein malnourished. Although protein malnutrition did not promote bacterial translocation from the gut to systemic organs, the protein-malnourished mice were more susceptible to endotoxin-induced bacterial translocation than normally nourished mice (p less than 0.01). Since the gross epithelial damage documented after endotoxin administration in normally nourished mice was diminished after protein malnutrition, there was no correlation between the gross appearance of the epithelial mucosal barrier and the extent of endotoxin-induced bacterial translocation. These results suggest that the synergistic effect of endotoxin plus protein malnutrition on bacterial translocation is not primarily related to failure of the gut mucosal barrier. Nonetheless, it appears that protein-malnourished mice are less able to clear translocating bacteria than normally nourished mice.     

肠外与肠内营养对胰腺外分泌和急性重症胰腺炎的影响

肠外营养(PN)不能改变胰腺炎自然病程,能降低并发症和病死率,但导管感染和肠源性并发症增加。近年来,肠内营养（EN）应用受到重视,但在急性重症胰腺炎（SAP）中的应用仍有争议。从EN对胰腺外分泌和SAP自然病程的影响分析,提出经空肠喂养不会刺激胰腺分泌,也不会加重SAP的病情。在临床实际应用中,应结合SAP的分期和临床状况,采用PN和EN联合应用来达到营养支持的目的。     

Endotoxin and cytokine released during parenteral nutrition

BACKGROUND: Apart from its benefits, parenteral nutrition (PN)-related complications have been reported. Studies have shown that PN could alter cytochrome P450 (CYP) activity. One of the possible mechanisms is through cytokine and nitrite release, which is triggered by endotoxin. The purpose of this study is to investigate the potential release of endotoxin, cytokines, and nitrite during PN. METHODS: Rats were randomly assigned into either (a) the PN group, which received continuous PN infusion only; or (b) the control group, which received normal chow with saline infusion. The infusions were administered continuously for 7 days, and then blood was collected and microsomes were prepared from the excised livers. RESULTS: Endotoxin levels in the PN group were significantly higher in portal vein but not in inferior vena cava when compared with those of the controls. TNF-alpha and IL-6 levels were significantly higher in the PN group (p < .05). However, IL-1 beta levels were not significantly different in the 2 groups (p > .05). The nitrite levels, the end product of nitric oxide formation, were found to be almost 2 times higher after PN (p < .05). CONCLUSIONS: It is confirmed that a 7-day infusion treatment of PN in rat may be linked to bacterial translocation, which leads to increased levels of endotoxin. This increase could trigger cytokine release, which could down regulate CYP activities.