Effects of L-arginine infusion during ischemia on gut blood perfusion, oxygen tension, and circulating myeloid cell activation in a murine gut ischemia/reperfusion model

BACKGROUND: Gut hypoperfusion is considered to be a mechanism for early multiple‐organ failure after severe surgical insults. L‐Arginine (ARG) may preserve gut microcirculation as a substrate of nitric oxide synthase, but simultaneously may enhance immune cell response. It remains unknown if ARG infusion during gut ischemia improves the outcome after gut ischemia‐reperfusion (I/R). METHODS: Male Institute of Cancer Research mice were randomized to control and ARG groups. After i.v. cannulation, mice underwent 90 (Exp. 1) or 60 (Exp. 2 and 3) minutes of gut I/R. Control mice received normal saline infusion at 1 mL/h for 60 minutes during ischemia, whereas the ARG group was given 1% ARG hydrochloride solution. In Exp. 1, survival was observed for 72 hours (n = 35). In Exp. 2, blood perfusion and oxygen tension of the small intestine were measured (n = 9). In Exp. 3, peripheral blood was obtained at 2 or 4 hours after reperfusion (n = 22). Reactive oxygen intermediate (ROI) production by myeloid cells with or without phorbol myristate acetate (PMA) stimulation and expression of CD11a and CD11b on myeloid cells were examined using flow cytometry. RESULTS: Exp. 1: There was no significant difference in survival times (log rank test, p =.2). However, survival rates at 12 hours were 72% (13/18) for the control group and 35% (6/17) for the ARG group (p <.05 Fisher). Exp. 2: ARG infusion significantly improved gut blood perfusion ratio during ischemia but had no effect on oxygen tension. Exp. 3: In the ARG group, ROI production with PMA and CD11b expression at 4 hours were higher than those at 2 hours, whereas there were no significant changes in the control mice. CONCLUSIONS: ARG infusion improves intestinal blood perfusion during ischemia but primes and activates circulating myeloid cells excessively. Consequently, i.v. infusion of ARG during ischemia reduces survival rate.     

Total parenteral nutrition supplementation with glutamine improves survival after gut ischemia/reperfusion

BACKGROUND: Total parenteral nutrition (TPN) alters gut cytokines and mucosal immunity and increases intercellular adhesion molecule-1 (ICAM-1) expression, gut neutrophil levels, and mortality after gut ischemia. Supplementation of TPN with glutamine partially supports mucosal immunity by preserving respiratory and intestinal IgA levels, maintaining the proper IgA-stimulating cytokine milieu within the intestine, and reducing intestinal ICAM-1 expression and neutrophil accumulation. This work investigates whether glutamine supplementation of TPN affects mortality in mice after gut ischemic insult. METHODS: Thirty-eight mice were randomized to receive chow, TPN, or 2% glutamine-supplemented TPN (GLN-TPN) for 5 days. After feeding their respective diets, gut ischemia/reperfusion (I/R) was induced with superior mesenteric artery occlusion for 30 minutes followed by resuscitation with 1 mL saline. Survival was recorded until 72 hours after reperfusion. RESULTS: Survival time was significantly reduced in the TPN-fed mice compared with both chow-fed and GLN-TPN-fed mice (p < .05). Survival at 72 hours after reperfusion was also significantly lower in the TPN-fed mice than in the chow-fed and GLN-TPN-fed mice (p < .05) CONCLUSIONS: Glutamine supplementation of TPN significantly improves survival after gut I/R, suggesting modulation of the inflammatory response or improved gut tolerance to low-flow states.     

Epidermal growth factor regulates intestinal glutamine uptake during total parenteral nutrition

Sprague Dawley rats were randomised into three groups: group I (chow) were fed rat chow and water ad libitum, group II total parenteral nutrition (TPN) received a standard formula of TPN, and group III (TPN--epidermal growth factor (EGF)) received the same TPN as group II and injections of EGF (0.1 microg/gm body weight) subcutaneously twice daily. Glutamine (GLN) concentrations in tissues and blood were measured by reversed phase high performance liquid chromatography. Gut GLN extraction was calculated by dividing the difference in GLN concentrations (Conc) between the carotid artery (ART) and portal vein (PV) by the arterial concentration [(ART Conc - PV Conc)/ART Conc]. TPN induced a marked reduction of GLN concentration in tissues and blood, and also reduction of gut GLN extraction. When EGF was administered along with TPN, gut GLN concentration did not fall and gut GLN extraction was increased by 15% (TPN - EGF 1 week, P < 0.05). Arterial blood concentration of GLN was increased when TPN and EGF were used for 1 week (P < 0.05 vs control). But EGF did not prevent the GLN concentration of other tissues decreasing during TPN. Our results suggest that EGF can regulate intestinal uptake of GLN during TPN.     

Influence of N-acetylglutamine or glutamine infusion on plasma amino acid concentrations during the early phase of small-bowel adaptation in the dog.

Glutamine is a nonessential neutral amino acid that is widely consumed by the intestinal tract in catabolic states. We have followed up the plasma amino acid profile after extensive small-bowel resection in dogs receiving total parenteral nutrition (TPN) with or without glutamine (GLN) or N-acetylglutamine (aGLN) supplementation. Animals were divided into four groups according to the type of surgery (enterectomy or transection) and nutrition (TPN, TPN with aGLN, or TPN with GLN). Plasma GLN levels decreased in group I (enterectomy and TPN) on day 2 (p = .03) and significantly increased on postoperative days in groups III (enterectomy and TPN with aGLN) and IV (enterectomy and TPN with GLN). A significant increase of plasma GLN was observed in groups III and IV compared with group I on days 6 and 8 (p = .03 and p = .01). Plasma alanine decreased in groups with bowel resection, whereas no change was observed in the control group (transection) and the decrease of plasma alanine was significantly less pronounced in groups III and IV compared with group I. The increase of crypt depth and villous height was more pronounced in groups III and IV. These results suggest that GLN is a required substrate for mucosal growth and function, which could improve the intestinal adaptation encountered after enterectomy.     

Single dose of glutamine enhances myocardial tissue metabolism, glutathione content, and improves myocardial function after ischemia-reperfusion injury

BACKGROUND: Myocardial ischemia and reperfusion (I/R) injury causes significant morbidity and mortality. Protection against I/R injury may occur via preservation of tissue metabolism and ATP content, preservation of reduced glutathione, and stimulation of heat shock protein (HSP) synthesis. Supplementation with glutamine (GLN) has been reported to have beneficial effects on all of these protective pathways. Thus, we hypothesized that GLN pretreatment given to the rat in vivo would protect the myocardium against I/R-induced dysfunction. METHODS: GLN (0.52 g/kg, intraperitoneally, given as alanine-glutamine dipeptide), alanine alone (0.23 g/kg), or a Ringer's lactate solution (control) was administered to Sprague-Dawley rats 18 hours before heart excision, perfusion, exposure to global ischemia (15 minutes) and reperfusion (1 hour). Tissue metabolites were analyzed via magnetic resonance spectroscopy. RESULTS: In control and alanine-treated animals, I/R injury resulted in cardiac dysfunction, indicated by a decrease in cardiac output. Administration of GLN 18 hours before I/R injury preserved cardiac output after reperfusion. Metabolic analysis of the myocardial tissue revealed that [/R injury led to significant diminution of myocardial tissue glutamate, ATP content, accumulation of myocardial lactate, and a reduction in reduced glutathione content in control animals. GLN significantly reduced the deleterious changes in myocardial metabolism and improved reduced glutathione content. No changes in pre- or post-I/R injury HSP expression were observed after GLN administration. CONCLUSIONS: These observations demonstrate that remote in vivo administration of GLN before cardiac I/R injury can improve post-I/R cardiac function. This effect may be mediated via improved myocardial metabolism and enhanced reduced glutathione content.     

Dietary restriction compromises resistance to gut ischemia-reperfusion, despite reduction in circulating leukocyte activation

BACKGROUND: Gut ischemia-reperfusion (gut I/R) accompanying severe surgical insults leads to neutrophil-mediated injury and is regarded as a triggering event in early multiple-organ failure. Our previous study demonstrated dietary restriction to down-regulate leukocyte activation. Therefore, we hypothesized dietary restriction might be beneficial in terms of surviving I/R. We also evaluated leukocyte activation and the level of organ glutathione, an antioxidative substance. METHODS: Institute of Cancer Research mice received chow, 170 (ad libitum), 119 (MR: mild restriction) or 68 (SR: severe restriction) g/kg per day for 7 days. Exp. 1: The mice (n = 59) underwent 15 or 45 minutes of gut ischemia and survival was observed. Exp. 2: The mice (n = 73) were killed before or 60 or 120 minutes after 15-minute ischemia. Reactive oxygen intermediate (ROI) production by circulating myeloid cells and CD11b expression was determined. Some mice were assessed for nuclear factor kappa B (NFkappaB) activation. Glutathione levels were measured in some of the small intestine and liver samples from each group. RESULTS: Dietary restriction decreased survival. Circulating myeloid cell priming and activation, in terms of ROI production and CD11b expression, were enhanced in the ad libitum group but not in the restricted groups. NFkappaB was activated only in the ad libitum group. Gut and hepatic glutathione levels were lower in the SR than in the ad libitum group. Dietary restriction caused histologic damages in gut, liver, and lung 120 minutes after reperfusion. CONCLUSIONS: Dietary restriction blunts leukocyte priming and activation after gut ischemic insult but worsens the outcome by, at least in part, decreasing antioxidative activities. Clinically, nutrition replenishment may be required to improve the outcome of gut hypoperfusion.     

Effect of glutamine supplementation on protein metabolism and glutathione in tumor-bearing rats

The effect of glutamine (GLN)-supplemented total parenteral nutrition (TPN) on tumor growth and protein metabolism was investigated in tumor-bearing rats. Six days after implantation of AH109A hepatoma, rats received isonitrogenous TPN without or with alanyl-glutamine (25% of total N) for a period of 6 days. Protein turnover was assessed by continuous infusion of l4C-leucine and levels of GLN and glutathione were determined in muscle, jejunum and liver. Diet had no effect on tumor parameters: weight (mean = 4.4 g), GLN and glutathione concentrations, protein synthesis rate and bromodeoxyuridine-labeling index. Body weight loss was less pronounced in the GLN group (-5.5 +/- 1.2 vs. -9.4 +/- 1.4 g/5d). Decrease in plasma and muscle GLN concentrations (-30% and -17% vs. healthy controls, respectively) was limited in tumor-bearing rats receiving GLN-enriched TPN (-15% and +3%). GLN-supplemented TPN increased muscle and jejunum fractional synthesis rates (36% and 25% vs. standard TPN, respectively) and reduced body protein breakdown in tumor-bearing animals (303 +/- 33 vs. 421 +/- 66 mumol Leu/Kg/h). Decrease in jejunum glutathione levels was partially abolished in the GLN group: -50% vs. -64% in the standard TPN group; no effect was noticed in other tissues. The authors conclude that GLN-supplemented TPN improves protein metabolism at both the whole body and the tissue level, and prevents GLN and glutathione deficiencies associated with tumor implantation.     

Albumin infusion after reperfusion prevents gut ischemia-reperfusion-induced gut-associated lymphoid tissue atrophy

BACKGROUND: Our recent study clarified that gut ischemia-reperfusion (I/R) causes gut-associated lymphoid tissue (GALT) mass atrophy, a possible mechanism for increased morbidity of infectious complications after severe surgical insults. Because albumin administration reportedly reduces hemorrhagic shock-induced lung injury, we hypothesized that albumin treatment prevents GALT atrophy due to gut I/R. METHODS: Male mice (n = 37) were randomized to albumin, normal saline, and sham groups. All groups underwent jugular vein catheter insertion. The albumin and normal saline groups underwent 75-minute occlusion of the superior mesenteric artery. During gut ischemia, all mice received normal saline infusions at 1.0 mL/h. The albumin group was given 5% bovine serum albumin in normal saline at 1.0 mL/h for 60 minutes after reperfusion, whereas the normal saline group received 0.9% sodium chloride at 1.0 mL/h. The sham group underwent laparotomy only. Mice were killed on day 1 or 7, and the entire small intestine was harvested. GALT lymphocytes were isolated and counted. Their phenotypes (alphabetaTCR, gammadeltaTCR, CD4, CD8, B220) were determined by flow cytometry. RESULTS: On day 1, the gut I/R groups showed significantly lower total lymphocyte and B cell numbers in Peyer's patches and the lamina propria than the sham group. However, the albumin infusion partially but significantly restored these cell numbers. On day 7, there were no significant differences in any of the parameters measured among the 3 groups. CONCLUSIONS: Albumin infusion after a gut ischemic insult may maintain gut immunity by preventing GALT atrophy.     

Oral and parenteral glutamine in bone marrow transplantation: a randomized, double-blind study.

BACKGROUND: Total parenteral nutrition (TPN) supplemented with glutamine (GLN) has been reported to be effective for patients with bone marrow transplantation (BMT). Our aim was to evaluate enteral and parenteral glutamine in patients undergoing BMT. METHODS: For evaluation of GLN in BMT, 66 patients with 43 hematologic and 23 solid malignancies (21 breast carcinomas), were randomized, double-blinded, to either oral GLN (n = 35) or glycine-control (GLY) (n = 31), 10 g three times daily. When TPN became necessary, patients who received GLN orally were given TPN with GLN (0.57 g/kg). Those who received GLY received standard TPN, isocaloric and isonitrogenous. Patients with hematologic malignancies received high-dose chemotherapy, total body irradiation, and either allogeneic (ALLO) BMT (n = 18) or autologous (AUTO) stem cell transplantation (n = 25). Patients with solid malignancies (n = 23) received AUTO. RESULTS: There were 14 in-hospital deaths without relationship to GLN administration. For respective comparisons of ALLO and AUTO transplants in the GLN and GLY hematologic groups and AUTO in the solid tumor groups, there were no significant differences in hospital stay, duration of stay after BMT, TPN days, neutrophil recovery >500/mm3, incidence of positive blood cultures, sepsis, mucositis, and diarrhea. Acute graft us host disease occurred in 1 of 10 hematologic patients receiving GLN and in 3 of 8 patients receiving GLY placebo (p > .05). Possible reduction in need for TPN and a suggestion of improved long-term survival were associated with GLN. CONCLUSIONS: Oral and parenteral GLN seemed to be of limited benefit for patients having AUTO or ALLO BMT for hematologic or solid malignancies. Further study of long-term effects of GLN in BMT seems warranted.     

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.     

双歧杆菌黏附素对大鼠肠缺血-再灌注损伤的防护作用

目的:研究双歧杆菌分泌型黏附素对大鼠缺血-再灌注(I/R)后肠黏膜屏障的防护作用。方法:将54只大鼠随机分为假手术组(对照组)、模型组(I/R组)和黏附素预处理组(实验组),每组各24只。于造模成功后6 h、第1、第4和第7天,分别取6只大鼠的血和小肠标本,观察小肠组织病理改变,检测各时间点血中肿瘤坏死因子-α(TNF-α)I、L-6I、L-10、二胺氧化酶(DAO)和D-乳酸(D-LAC)的活性和含量。结果:与对照组比较I,/R组血中TNF-αI、L-6I、L-10、DAO和D-乳酸水平在各时相点均升高(P<0.05);与I/R组比较,实验组各时间点IL-6和DAO水平明显降低(P<0.05),TNF-α浓度术后第1天低于I/R组(P<0.05),术后第4和第7天实验组大鼠血浆D-LAC浓度明显低于I/R组(P<0.05),小肠病理改变较I/R组减轻(P<0.05)。结论:双歧杆菌黏附素对大鼠I/R后肠黏膜屏障具有防护作用,能减轻肠黏膜的I/R损伤。     

Specific intraluminal nutrients alter mucosal blood flow during gut ischemia/reperfusion

BACKGROUND: We have previously demonstrated in a rodent model the differential effects that specific intraluminal nutrients exert on gut ischemia/reperfusion (I/R) injury. Alanine was shown to amplify, whereas glucose protected against, gut I/R injury and associated gut dysfunction. The objective of this study was to determine whether these specific nutrients are associated with alterations in mucosal perfusion during gut I/R. METHODS: Sprague-Dawley rats had either a laser doppler probe or a tonometer inserted into a jejunal sac filled with either 10 mmol/L alanine, glucose, or mannitol (osmotic control) followed by 60 minutes of superior mesenteric artery occlusion and 60 minutes of reperfusion. Laser doppler mucosal blood flow and regional PCO2 (PrCO2) measurements were obtained. RESULTS: Mucosal blood flow was significantly increased during both ischemia and reperfusion when intraluminal glucose was present compared with intraluminal alanine. Blood flow changes were reflected by lower jejunal PrCO2 measurements with intraluminal glucose compared with intraluminal alanine. CONCLUSIONS: Intraluminal glucose can augment mucosal blood flow during gut I/R and may explain the protective effect we previously observed.     

肠内或肠外营养对手术后病人的氮平衡、 肠通透性、血浆氨基酸及费用等的影响

目的观察肠内营养、肠外营养对手术后病人的的氮平衡、肠通透性、费用等影响。对象 和方法随机、对照、多中心临床研究。60例合乎计划要求的食道、胃、结肠道手术的患者为对象。按随机表进入研究组或对照组，两组为等氮等热卡营养摄入。研究计划经伦理委员会批准。所有病人均知情同意参加。结果(1)安全性两组均无严重不良事件，对照组有2例肝功损害，研究组无肝功损害（P=0.19）。(2)替代(Surrogateefficacy)有效性指标(Endpointmarkers)(1)氮平衡研究组累积氮平衡为(108±107)mg     

大鼠肠道缺血/再灌注时肠淋巴干结扎对肠道屏障的影响

目的比较大鼠肠道缺血/再灌注时肠淋巴干结扎与不结扎对肠道屏障的影响,探讨肠道淋巴及肠道屏障功能在危重病发生中的作用。方法健康雄性SPF级SD大鼠随机分为4组:空白组、假手术组、肠道缺血/再灌注组、肠道缺血/再灌注 淋巴干结扎组。分别检测肠道损伤程度,细菌、内毒素的移位情况及循环中D-乳酸、二胺氧化酶(DAO)的水平。结果假手术组、肠道缺血/再灌注组、肠道缺血/再灌注 淋巴干结扎组的黏膜厚度及绒毛高度均较空白组显著降低(P<0.05),肠道缺血/再灌注组、肠道缺血/再灌注 淋巴干结扎组间差异无显著性;空白组、假手术组未检测到细菌移位,肠道缺血/再灌注组细菌移位率为40%,肠道缺血/再灌注 淋巴干结扎组细菌移位率为20%;内毒素水平肠道缺血/再灌注组最高,肠道缺血/再灌注 淋巴干结扎组较肠道缺血/再灌注组显著降低(P<0.05),但肠道缺血/再灌注组、肠道缺血/再灌注 淋巴干结扎组均较空白组、假手术组增高(P<0.05);肠道缺血/再灌注组、肠道缺血/再灌注 淋巴干结扎组D-乳酸与DAO水平较空白组、假手术组显著增加(P<0.05),且肠道缺血/再灌注组高于肠道缺血/再灌注 淋巴干结扎组(P<0.05)。结论肠道缺血/再灌注损伤可导致肠黏膜厚度和绒毛高度显著降低,肠淋巴干结扎对肠道形态虽无明显保护作用,但减少细菌在肠系膜淋巴结的定植并降低血循环中内毒素、D-乳酸与DAO的水平。     

低温卡托普利局部灌注对缺血再灌注后脊髓组织自由基和MPO的影响

目的观察低温卡托普利局部灌注对兔脊髓缺血再灌注后脊髓组织氧自由基、髓过氧化物酶（MPO）的影响。方法80只成年新西兰白兔随机分成4组，A组：假手术组（n=8）；B组：缺血对照组（n=24）；C组（n=24）：低温生理盐水局部灌注；D组（n=24）：低温生理盐水和卡托普利（4mg／kg）局部灌注。建立兔脊髓缺血损伤模型，经主动脉阻断段灌注保护液；采用化学比色法测定再灌注后8h、24h及72h脊髓组织MDA含量，黄嘌呤氧化酶法测定SOD活力，检测MPO活力。结果脊髓缺血再灌注后组织MDA含量升高，SOD活力下降，MPO活性增强；C组、D组与B组比较，MDA含量在各时相点均下降（P〈0．01），MPO活力明显降低（P〈0．01），脊髓组织MDA与动物后肢神经功能评分之间呈负相关。结论低温溶液可减少脊髓缺血再灌注后氧自由基的生成，减轻中性粒细胞浸润，联合卡托普利局部灌注，具有协同保护脊髓的作用。     

谷氨酰胺和生长激素对术后病人肌肉代谢的影响

目的许多研究表明,给予生长激素和谷氨酰胺能减少手术后肌肉蛋白的分解(术后肌蛋白分解表现在肌蛋白合成减少、谷氨酰胺水平降低和氮丢失增加)。本研究目的是联合使用生长激素和胰岛素样生长因子((IGF-I,一种能解释生长激素部分作用效果的生长因子)及添加生长激素和谷氨酰胺对术后肌肉代谢的影响。     

抗肿瘤坏死因子α单克隆抗体对急性胰腺炎大鼠肠道完整性的影响

目的：探讨抗肿瘤坏死因子α单克隆抗体（anti-TNFαMcAb)对急性胰腺炎大鼠所致道完整性的影响。方法：SD大鼠32只,制备急性胰腺炎模型后,随机分为对照组（n=16)及实验组（n=16),对照组给予全肠外营养支持,实验组给予相同配方的全外营养支持;并予anti-TNFαMcAb静脉内注射。于建立急性胰腺炎模型后第1天及第5天处死,检测大鼠肠道通透性、吸收功能、空肠粘膜湿重、微绒毛高度和面积、双糖酶活性以及肠道细菌移位率。结果：两组动物间肠道通透性,吸收功能、空肠粘膜湿重、微绒毛高度和面积、双糖酶活性以及肠道细菌移位率均无显著差别。结论：anti-TNFαMcAb对急性胰腺炎大鼠肠道完整性无明显影响。     

Glutamine Administration After Sublethal Lower Limb Ischemia Reduces Inflammatory Reaction and Offers Organ Protection in Ischemia/Reperfusion Injury

Background: This study investigated the effects of intravenous glutamine (GLN) administration on the expression of adhesion molecules and inflammatory mediators in a mice model of hind limb ischemia/reperfusion (IR) injury. Methods: There were 3 IR groups and 1 normal control (NC) group. The NC group did not undergo the IR procedure. Mice in the IR groups underwent 90 minutes of limb ischemia followed by a variable period of reperfusion. Ischemia was performed by applying a 4.5‐oz orthodontic rubber band to the left thigh. Mice in one IR group were sacrificed immediately after reperfusion. The other 2 IR groups were injected once with either 0.75 g GLN/kg body weight (G group) or an equal volume of saline (S group) via tail vein before reperfusion. Mice in the S and G groups were subdivided and sacrificed at 4 or 24 hours after reperfusion. Results: IR enhanced the inflammatory cytokine gene expressions in muscle. Also, plasma interleukin (IL)–6 levels, blood neutrophil percentage, and the adhesion molecule and chemokine receptors expressed by leukocytes were upregulated after reperfusion. The IR‐induced muscle inflammatory mediator gene expressions, blood macrophage percentage, and plasma IL‐6 concentration had declined at an early or a late phase of reperfusion when GLN was administered. Histologic findings also found that remote lung injury was attenuated during IR insult. Conclusions: A single dose of GLN administration immediately after sublethal lower limb ischemia reduces the inflammatory reaction locally and systemically; this may offer local and distant organ protection in hind limb IR injury.     

谷氨酰胺和重组人生长激素对门静脉高压症患者术后肠黏膜屏障功能的影响

目的研究单独或联合应用谷氨酰胺（Gln）和重组人生长激素（rhGH）对门静脉高压症患者术后肠黏膜屏障功能的影响。方法将29例肝硬化门静脉高压症接受手术治疗的患者随机分为4组：Gln组（n=6）、rhGH组（n=8）、Gln＋rhGH组（n=7）和对照组（n=8）。术后3天开始进行等氮、等热量的全胃肠外营养（TPN）支持，持续7天。对患者手术前、后的尿乳果糖／甘露醇（L／M）、十二指肠降段黏膜绒毛高度及陷窝深度进行测定。结果Gln＋rhGH组L／M升高的幅度显著小于对照组（P〈0．05），Gln和rhGH组与对照组比较差异无显著性。Gln＋rhGH组肠黏膜绒毛高度和陷窝深度均大于对照组（P〈0．05），Gln和rhGH组与对照组比较差异无显著性（P〉0．05）。Gln＋rhGH组术后绒毛高度及陷窝深度均显著大于术前（P〈0．05）；对照组术后绒毛高度小于术前（P〈0．05），陷窝深度差异无显著性（P〉0．05）；Gln和rhGH组手术前、后绒毛高度及陷窝深度差异无显著性（P〉0．05）。结论联合应用Gln和rhGH能降低门静脉高压症患者术后肠壁通透性并维护肠黏膜形态学完整性，单独应用Gln或rhGH无此作用。     

Combination of recombinant human growth hormone and glutamine-enriched total parenteral nutrition to surgical patients: effects on circulating amino acids

BACKGROUND & AIMS: Both recombinant human growth hormone (rhGH) and glutamine (GLN) may have beneficial anabolic actions on amino acid metabolism. The aim of this study was to evaluate the additive effects of rhGH and GLN on plasma amino acids postoperatively. METHODS: 31 females undergoing laparoscopic cholecystectomy were randomized to three groups: Group I (n=10) received 13 IU/m(2) of rhGH the morning of surgery and the following three postoperative days, together with glutamine-free TPN for the first two postoperative days. Group II (n=11) received rhGH as the first group, together with glutamine-enriched (7 g GLN/m(2)/day) TPN. Group III (n=10) received glutamine-enriched TPN as the second group, but rhGH was replaced by placebo. Daily plasma amino acid concentrations and nitrogen balance were determined. RESULTS: In the GH treated groups, the plasma concentrations of several amino acids were decreased on the third postoperative day, compared to preoperatively. This was not observed in Group III. The changes were more pronounced in Group II. In Group II the negative AV-differences of amino acids tended to be attenuated, while the patients in Group III had increased negative AV-differences. The cumulative nitrogen balance was significantly improved in the GH groups, compared with Group III. CONCLUSION: The combined treatment of growth hormone and glutamine has additive effects on AV-balances of amino acids postoperatively, whereas nitrogen balance is not further improved when adding glutamine to rhGH treatment.