富含谷氨酰胺二肽的新型氨基酸对全肠外营养短肠综合征大？…

目的 观察富含谷氨酰胺二肽的新型氨基酸对Ｗｉｓｔａｒ大鼠短肠模型血清蛋白和肝功能的影响及探讨其减轻脂肪乳剂引起肝损害的作用机制。方法 ３０只Ｗｉｓｔａｒ雄性在鼠随机分为富含谷氨酰胺二肽新型氨基酸组（２０ＡＡ组）、标准组（１７ＡＡ组）、无氮组,观察不同组动物之间血清总蛋白、白蛋白、前白蛋白（ｐｒｅ－ａｌｂｕｍｉｎ,ＰＡ）、纤维结合蛋白（ｆｉｂｒｏｎｅｃｔｉｎ,ＦＮ）以及丙氨酸转氮酶和胆红素的变化。结     

谷氨酰胺对短肠综合征大鼠残留小肠代偿作用的影响

目的观察谷氨酰胺对短肠综合征大鼠残留小肠代偿作用的影响.方法23只雄性SD大鼠切除80%小肠,随机分三组饮食组(n=8)术后自由进食;全胃肠外营养(TPN)组(n=8)输TPN标准液;谷氨酰胺(Gln)组(n=7)输TPN+Gln;正常大鼠8只,作为正常对照组.术后第7天,称体重,取回盲部淋巴结和门静脉血作细菌培养,取残留空肠和回肠进行组织学检查(包括光镜和电镜).结果饮食组和Gln组术后体重有明显差异饮食组、TPN组和Gln组回盲部淋巴结和门静脉血细菌培养阳性率无明显差别,但TPN组细菌培养阳性率高于Gln组;饮食组空肠粘膜绒毛高度(VH)和粘膜厚度(MT)、回肠粘膜VH均明显大于正常组;正常组空肠粘膜VH、MT明显大于TPN组,正常组回肠粘膜隐窝深度(CD)、MT明显大于TPN组;Gln组空肠和回肠粘膜VH、CD和MT明显大于TPN组.结论80%小肠切除后,残留小肠发生代偿性改变,食物刺激是残留小肠代偿的重要因素;但这种代偿不完全,补充TPN可维持机体生理平衡,TPN引起残留小肠粘膜萎缩;Gln可阻止TPN引起残留小肠粘膜萎缩,促进残留小肠代偿.     

含谷氨酰胺二肽全肠外营养对急性放射性小肠炎的营养作用

作者将３４只Ｓｐｒａｇｕｅ－Ｄａｗｌｅｙ大鼠随机分四组，Ａ组不含丙氨酰－谷氨酰胺二肽（Ａｌａ－Ｇｌｎ），而给予相庆量的甘，丝，丙及肺氨酸的常规全肠外营养（ＰＴＮ－Ｃｏｎｖ）；Ｂ组含Ａｌａ－Ｇｌｎ的全肠外营养（ＴＰＮ－Ｇｌｎ）；两组间的热，氮及液体量相同。Ｃ组为消化道营养组。Ｄ组为正常组。实验组合予８戈瑞（ＧＹ）剂量全腹照射，然后分别给予ＴＰＮ及肠道营养７知。观察在急性谢性小肠炎时，Ａｌａ－Ｇｌｎ作     

谷氨酸胺对短肠综合征大鼠残留小肠代偿作用的影响

目的;观察谷氨酰胺对短肠综合征大鼠残留小肠代偿作用的影响。方法：２３只雄性ＳＤ大鼠切除８０％小肠,随机分三组;饮食组（ｎ＝８）术后自由进食：全胃肠外营养（ＴＰＮ）组（ｎ＝８）输ＴＰＮ标准液;谷氨酸胺（Ｇｌｎ）组（ｎ＝７）输ＴＰＮ＋Ｇｌｎ;正常大鼠８只,作为正常对照组。术后第７天,称体重,取回盲部淋巴结和门静脉血作细菌培养,取残留空肠和回肠进行组织学检查。     

谷氨酰胺和生长激素对短肠综合征患者肠道代偿作用

目的探讨谷氨酰胺和生长激素对短肠综合征(SBS)患者的肠道代偿作用。方法26例短肠综合征患者残余小肠长度为0～100(中位数42.5)cm,手术后接受肠外营养(PN)支持3-52个月,联合应用生长激素(GH)(0.10±0.06)mg·kg-1·d-1和谷氨酰胺(GLN)(0.30±0.17)g·kg-1·d-1进行肠道促代偿治疗。结果26例接受GH加GLN治疗的SBS患者,其中9例(34.6%)治疗后近期内完全摆脱PN;8例(30.8%)经治疗后明显减少了PN用量,从每周需要PN(6.0±1.0)d下降至(4.2±1.0)d,每周PN需要量从(13.6±5.2)L降至(8.2±3.3)L;9例(34.6%)在治疗后仍依赖PN维持。结论经过合适的营养支持和肠道促代偿治疗,大多数短肠综合征患者残留肠道能充分代偿,完全摆脱PN或减少PN用量,长期健康生存。     

谷氨酰胺对短肠综合征大鼠结肠黏膜细胞凋亡的影响

目的 探讨谷氨酰胺联合肠内营养对动物模型结肠黏膜凋亡的影响。方法 将大鼠随机分为3组，即正常组，模型组、谷氨酰胺组2l天两个时间点进行观察。结果 谷氨酰胺组BCl-2的平均灰度值及表达阳性的面积明显大于其他组，Bax基因蛋白平均灰度值及表达阳性的面积明显小于其他组（P〈0．05）。结论 谷氨酰胺能抑制结肠黏膜细胞的凋亡，促进结肠的代偿。     

谷氨酰胺对短肠综合征大鼠模型结肠黏膜作用的初步研究

目的 探讨谷氨酰胺联合肠内营养对动物模型结肠黏膜的影响。方法 将大鼠随机分为5组，即模型肠内营养组、谷氨酰胺大剂量＋肠内营养组，谷氨酰胺中剂量＋肠内营养组，谷氨酰胺小剂量＋肠内营养组。分为7天，14天2个时间点进行观察。结果 Gln各组肠壁肌层增厚明显，皱襞明显增高，肠腺数量增多，其中大、中剂量组的皱襞不仅高且密集，皱襞高度、肠腺密度均明显大于模型组（P〈0．01）。结论 谷氨酰胺＋肠内营养比单用营养的模型组更可以促进大鼠结肠的代偿，大、中剂量组优于小剂量组。     

谷氨酰胺在肠外营养中的应用

谷氨酰胺具有许多重要的生理功能，动物实验证明ＧＬＮ能预防肠外营养所致的肝，肠，胰损害，在人体中应用谷氨酰胺安全可行，并具有改善机体代谢的功能，二肽ＧＬＮ比ＧＬＮ单体具有更大的溶解度且更稳定，在肠外营养中的应用具有广阔的前景。     

含谷氨酰胺二肽全肠外营养对急性放射性小肠炎的营养作用

作者将３４只Ｓｐｒａｇｕｅ－Ｄａｗｌｅｙ大鼠随机分四组，Ａ组不含丙氨酰－谷氨酰胺二肽（Ａｌａ－Ｇｌｎ），而给予相应量的甘、丝、丙及脯氨酸的常规全肠外营养（ＴＰＮ－Ｃｏｎｖ）；Ｂ组含Ａｌａ－Ｇｌｎ的全肠外营养（ＴＰＮ－Ｇｌｎ）；两组间的热、氮及液体量相同。Ｃ组为消化道营养组。Ｄ组为正常组。实验组给予８戈瑞（ＧＹ）剂量全腹照射，然后分别给予ＴＰＮ及肠道营养７天。观察在急性放射性小肠炎时，Ａｌａ－Ｇｌｎ作为Ｇｌｎ源对小肠的代谢、结构及功能的影响，及经消化道营养的作用。实验结果表明，Ｂ组动脉血Ｇｌｎ浓度显著高于其它各组（Ｐ＜０．０５），说明Ａｌａ－Ｇｌｎ二肽输入后迅速分解为游离谷氨酰胺，利于组织使用。其小肠蛋白质和ＤＮＡ含量优于Ａ组。形态学结果显示组Ｂ小肠壁全层厚度、粘膜厚度及绒毛高度显著高于Ａ和Ｃ组（Ｐ＜０．０００１），且小肠腺窝细胞平均分裂数高于Ａ和Ｃ组（Ｐ＜０．０５），肠道内细菌移位率亦低于Ａ和Ｃ组（Ｐ＜０．０５）。粘液血便及体重降低以Ａ、Ｃ组为重。Ｃ组的摄食量不足，氮和热量摄取低于Ａ、Ｂ组，其体重下降超过Ｂ组。Ｃ组８只实验大鼠死亡２只，其中１只为末段回肠穿孔。Ａ、Ｂ组中无１例发生死亡及并发症。     

谷氨酰胺肠外营养对大鼠移植小肠营养作用的研究

作者研究了加谷氨酰胺的肠外营养对大鼠移植小肠萎缩及功能低下的预防作用。对Ｗｉｓｔａｒ鼠行近段空肠移植,然后给予肠外营养１０天。实验组给予加３％丙氨酰－谷氨酰胺的营养液,而对照组给予含等氮量非必需氨基酸的营养液。结果显示：实验组移植小肠的绒毛高度、粘膜厚度、腺窝深度和绒毛表面积均明显大于对照组;实验组移植小肠粘膜上皮细胞的超微结构基本保持完好,而对照组则出现线粒体肿胀,嵴断裂和微绒毛萎缩。实验组移植小肠对１５Ｎ－甘氨酸的吸收率明显高于对照组。结果提示：加谷氨酰胺的肠外营养能促进大鼠移植小肠粘膜增生,维持粘膜细胞超微结构的完整,并能改善其对氨基酸的吸收能力。     

全小肠切除患者家庭肠外营养16年的代谢研究

目的：探讨家庭肠外营养（HPN）患者的代谢变化及并发症。方法：总结1例全小肠及右半结肠切除并接受家庭肠外营养支持16年的临床资料，分析其不同阶段的代谢状态。结果：患者在接受肠外营养5年后妊娠，产下1健康女婴，在16年中，肝功能各项指标基本正常，每根静脉导管的平均留置时间为240d，最长1根导管使用26个月，而且导管感染率仅为0．2次／年，但先后曾出现贫血，低锌血症及高铁等代谢异常，其脂质过氧化及DNA损害，尿中8－OH Gua值（66．8fmol/ug DNA）等明显高于正常值，结论：长期HPN患者可出现一系列代谢，感染等并发症，应积极防治导管的堵塞与感染，并根据患者情况合理调整其营养配方。     

Influence of glutamine-supplemented parenteral nutrition on intestinal amino acid metabolism in rats after small bowel resection

Glutamine (Gln)-supplemented total parenteral nutrition (TPN) has been shown to improve mucosal adaptation after massive small bowel resection (SBR); however, its influences on intestinal amino acid metabolism remain unknown. In this study, intestinal amino acid flux, circulating plasma aminogram, mucosal glutaminase activity and protein, and DNA content were measured 7 days after massive SBR in rats receiving either standard (Std) or Gln-supplemented TPN. Sham-operated rats and rats fed chow after enterectomy served as controls. The uptake of Gln and the release of citrulline (Cit) by the remaining intestine was significantly decreased, with reduced mucosal glutaminase activity after SBR in the Chow and Std-TPN groups. Glutamine supplementation resulted in significantly increased gut Gln uptake compared with Std-TPN (P<0.01). Mucosal glutaminase activity, mucosal protein, and DNA content was also increased by Gln; however, the gut release of Cit remained unchanged (P>0.05). The subsequent decrease in circulating arginine (Arg) in the Gln-TPN group compared with the Std-TPN group (P<0.05) was attributed to an insufficient exogenous supply. These findings show that Gln-supplemented TPN improves mucosal growth and gut Gln uptake after SBR. However, the intestinal production of Cit, which remained low in both TPN groups, may lead to an insufficiency of endogenous Arg synthesis. Thus, both Gln and Arg may be essential amino acids after SBR.     

Relationship between serum citrulline levels and progression to parenteral nutrition independence in children with short bowel syndrome

Objective

Although bowel length is an important prognostic variable used in the management of children with short bowel syndrome (SBS), reliable measurements can be difficult to obtain. Plasma citrulline (CIT) levels have been proposed as surrogate markers for bowel length and function. We sought to evaluate the relationship between CIT and parenteral nutrition (PN) independence in children with SBS.

Study Design

A retrospective chart review performed for all patients seen in a multidisciplinary pediatric intestinal rehabilitation clinic with a recorded CIT between January 2005 and December 2007 (n = 27).

Results

Median age at time of CIT determination was 2.4 years. Diagnoses included necrotizing enterocolitis (26%), intestinal atresias (19%), and gastroschisis (22%). Citrulline levels correlated well with bowel length (R = 0.73; P < .0001) and was a strong predictor of PN independence (P Wilcoxon = 0.002; area under the receiver operating characteristic curve = 0.88; 95% confidence interval, 0.75-1.00). The optimal CIT cutoff point distinguishing patients who reached PN independence was 15 μmol/L (sensitivity = 89%; specificity = 78%).

Conclusion

Plasma CIT levels are strong predictors of PN independence in children with SBS and correlate well with a patient's recorded bowel length. A cutoff CIT level of 15 μmol/L may serve as a prognostic measure in counseling patients regarding the likelihood of future PN independence.     

The role of enteral nutrition in the reversal of parenteral nutrition-associated liver dysfunction in infants

Background

Liver dysfunction in children dependent on parenteral nutrition (PN) is well established, and the extent of hyperbilirubinemia has been shown to correlate with morbidity and mortality. The aim of this study was to assess whether increasing provisions of enteral nutrition can improve PN-associated hyperbilirubinemia over time.

Methods

A retrospective review was conducted on infants in our institution's Short Bowel Syndrome Clinic from 1999 to 2004. Inclusion criteria included PN duration more than 1 month, serum direct bilirubin more than 3 mg/dL while on PN, and tolerance of full enteral nutrition with eventual discontinuation of PN. Paired t tests were used for statistical analyses.

Results

Twelve infants were identified with a PN duration of 5 ± 1 months. Five patients underwent liver biopsy while on PN, and histological evidence of cholestasis was found on all specimens. Peak total and direct bilirubin levels were 10.5 ± 1.9 and 7.0 ± 1.6 mg/dL, respectively, and occurred at time of PN discontinuation. Only 2 patients had improvement in serum bilirubin levels before initiation of full enteral nutrition. After initiation of full enteral nutrition and discontinuation of PN, all patients achieved permanent normalization of bilirubin levels by 4 months (P < .05) after a 1-month plateau phase. Alkaline phosphatase levels approached reference range within this time but were not significant.

Conclusion

These data demonstrate for the first time that although PN-dependent infants can achieve normalization of marked hyperbilirubinemia with enteral nutrition, the improvement in liver function usually begins only after full enteral nutrition is tolerated and PN is withdrawn. These findings support the aggressive weaning of PN to enteral nutrition in infants with short bowel syndrome.     

生长激素对短肠大鼠残留小肠形态及生长代谢的影响

目的　探讨单纯肠外营养 (PN)与添加生长激素 (GH)的PN对短肠大鼠残留小肠代偿的作用及作用机制。方法　将 2 0只短肠SD大鼠随机分成PN组及PN rhGH组。行细胞增殖核抗原 (PCNA)测定、原位末端标记 (TUNEL)染色及bcl 2、BaxmRNA测定。结果　PN组残留小肠粘膜明显萎缩 ,PN rhGH组肠萎缩显著改善。PCNA表达在PN组降低 [(8.37± 2 .2 3)个 /视野 ],PN rhGH组增高 [(19.2 8± 3.2 5 )个 /视野 ],差异有非常显著性 (P <0 .0 1)。凋亡指数在PN组增高 [(2 2 .32± 3.84)个 / 10 0细胞 ],PN rhGH组降低 [(8.0 6± 2 .2 3)个 / 10 0细胞 ],差异有非常显著性(P <0 .0 1)。bcl 2mRNA表达在PN组降低 (0 .2 0± 0 .0 3) ,在PN rhGH组增高 (0 .44± 0 .0 6 ) ,BaxmRNA表达则相反。结论　单纯PN使短肠大鼠残留小肠粘膜明显萎缩 ,rhGH通过促进肠粘膜上皮细胞增生与抑制肠粘膜上皮细胞凋亡 ,显著促进残留小肠的代偿适应。     

含不同脂肪乳剂的肠外营养对肝移植大鼠肝脏功能的影响

目的　研究含不同脂肪乳剂的肠外营养 (TPN)对肝移植大鼠肝脏功能的影响。方法　建立肝移植大鼠模型 ,按照提供的能源不同分为单糖 (GLU )、脂肪乳剂MCT/LCT、LCT、STG 4个组 ,实验期为 7d ,记录实验期内动物死亡情况 ,于TPN后第 1、4、7d收集标本 ,检测AKBR(动脉血酮体比值 )、血ALT、AST、血TBIL。以正常和肝移植大鼠作为对照。结果　单糖组 7d动物死亡率显著高于脂肪乳剂组 (5 0 %vs0 % )。与脂肪乳组相比 ,单糖组动物 7d内血清ALT和AST水平降低缓慢、TBIL水平持续显著升高 ,AKBR水平在TPN后 1d恢复并稳定于较高水平 ,但于 7d时显著降低。在 1、4d时STG组动物血清ALT降低较MCT/LCTTPN组及LCTTPN组更为显著 ,MCT/LCTTPN组血清ALT水平低于LCTTPN组。结论　单糖TPN加重移植肝脏功能损害 ,动物死亡率增高 ,含脂肪乳的TPN能促进移植肝功能恢复。在减轻移植肝功能损害方面的优越性 ,依次为STG、MCT/LCT和LCT。     

门腔分流术后不同氨基酸溶液胃肠外营养的对比研究

目的　评价不同氨基酸溶液胃肠外营养对营养支持效果以及对肝脏功能和血浆氨基酸谱的影响。方法　因门脉高压症住院接受脾切除、限制性门腔静脉侧侧分流术的４０ 例肝功能Ｃｈｉｌｄ Ａ级患者,随机分为两组：Ｈｅｐａ 组和Ｖａｍｉｎ 组,每组各２０ 例。自手术后第１ 天起两组分别接受等氮、等热卡胃肠外营养支持８ 天（Ｈｅｐａ 组以Ｈｅｐａ 氨基酸溶液作为氮源,Ｖａｍｉｎ 组Ｖａｍｉｎ 氨基酸溶液作为氮源）。结果　两组累积氮平衡差异无显著性Ｈｅｐａ;营养支持８ 天后Ｈｅｐａ 组碱性磷酸酶水平显著低于Ｖａｍｉｎ 组（ Ｐ＜０．０５） ;营养支持８ 天后Ｈｅｐａ 组血氨水平显著低于Ｖａｍｉｎ 组（ Ｐ＜ ０－０５） ;Ｈｅｐａ 组血浆支链氨基酸（ＢＣＡＡ） 水平显著高于Ｖａｍｉｎ 组;Ｖａｍｉｎ 组血浆芳香族氨基酸（ＡＡＡ） 水平显著高于Ｈｅｐａ 组;Ｖａｍｉｎ 组血浆蛋氨酸（ＭＥＴＨ） 水平显著高于手术前水平（ Ｐ＜ ０－０１）。Ｈｅｐａ 组ＢＣＡＡ／ＡＡＡ〔（ＶＡＬ＋ ＬＥＵ＋ＩＬＥＵ）／（ＰＨＥ＋ ＴＹＲ）〕显著高于Ｖａｍｉｎ 组（ Ｐ＜ ０－０５）。结论　以Ｈｅｐａ 氨基酸溶液作为氮源可以取得与平衡型氨基酸溶液相似的营养支持效果;对于肝脏功能的损害方面,Ｈｅ     

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目的 探讨Hepa氨基酸溶液对非肝硬化和肝硬化肝癌病人行肝切除术后肠外营养的应用价值。方法 2002年2～5月对22例肝癌病人行肝切除术，术后接受含有Hepa氨基酸溶液的肠外营养6d，根据是否合并肝硬化分为两组，非肝硬化组7例，肝硬化组15例。术前和术后第7天抽血测定肝功能、血糖、前白蛋白、转铁蛋白和CD3、CD4、CD8、CD56。结果 术后第7天，非肝硬化组血清AST、ALT比肝硬化组恢复快，但血清ALP、TBIL比肝硬化组高，且肝硬化组血清ALB明显高于非肝硬化组；血清前白蛋白，转铁蛋白水平均降低，但非肝硬化组降低更明显；非肝硬化组外周血CD56降低明显。结论 Hepa氨基酸溶液更适合用于肝硬化肝癌术后的肠外营养。     

Massive small bowel resection in neonates—Is weaning from parenteral nutrition the final goal?

Eight surviving cases from an original 15 pediatric patients who underwent massive small bowel resection during their neonatal period were reviewed for a period of 2–19 years to assess long-term prognosis. the primary diseases were congenital intestinal atresia in 6 cases and midgut volvulus in 2. The length of the residual small intestine ranged from 27–75 cm and the ileocaecal valve had been resected in 3 cases. All cases were able to be weaned from parenteral nutrition and at present, 6 of the children can tolerate normal meals but 2 are still receiving enteral nutrition, in the form of a low residue diet at home. Near normal somatic growth was achieved in the most recent 5 cases who received intensive nutritional treatment in the immediate postoperative period, whereas 3 who did not receive nutritional management exhibited growth retardation. The D-Xylose absorption test revealed gradual improvement and finally normal absorption in all except one case with the shortest remaining intestine (27 cm). However, the fat absorption test revealed abnormal absorption in cases with a residual intestine of less than 45 cm. Late metabolic complications such as renal calculi, cholelithiasis and pathologic fractures were encoutered in 3 cases.     

Relationship between biopsy-proven parenteralnutrition-associated liver fibrosis and biochemical cholestasis in children with short bowel syndrome

Purpose

The aim of the study was to determine the frequency of biochemical cholestasis (direct bilirubin [DB] ≥2 mg/dL) in children with short bowel syndrome and biopsy-proven parenteral nutrition (PN)-associated liver disease and to define predictive factors for the occurrence and degree of hepatic fibrosis.

Methods

After institutional review board approval, a retrospective review was conducted of patients followed by 2 multidisciplinary intestinal rehabilitation programs between January 1, 2000, and September 30, 2008. Inclusion criteria were exposure to PN (>30 days) and having undergone a liver biopsy. Liver biopsy specimens were graded from 0 to 3 based upon degree of fibrosis in the pathology report. The most recent DB within 10 days before biopsy was recorded.

Results

A total of 66 children underwent 83 liver biopsy procedures. The most common diagnoses included necrotizing enterocolitis (NEC) (36.4%), gastroschisis (22.7%), and intestinal atresia (15.1%). Median age at biopsy was 6.1 months with a median duration of PN of 4.7 months. Of the patients, 70.3% had a history of exposure to parenteral ω-3 lipid emulsion. Of the liver biopsy specimens, 89% (74/83) demonstrated some degree of fibrosis (fibrosis scale 1-3), including 9.6% (8/83) with evidence of cirrhosis. 83% of biopsies without fibrosis and 55% of biopsies with fibrosis were obtained in patients without evidence of biochemical cholestasis (P = .20). Three (37%) of the 8 patients with cirrhosis on liver biopsy had no evidence of biochemical cholestasis. Univariate analysis identified only gestational age (GA) at birth as significantly associated with the degree of liver fibrosis (P = .03). A multivariate logistic regression model accounting for multiple biopsy procedures in patients revealed that GA was a predictor of fibrosis only in patients with a diagnosis other than NEC (P < .01).

Conclusions

In children with short bowel syndrome, biochemical cholestasis does not reflect the presence or degree of histologically confirmed PN-associated liver fibrosis. Careful follow-up, combined with further refinement of diagnostic and hepatoprotective strategies, may be warranted in this patient population.