谷氨酰胺对放射损伤大鼠蛋白质代谢的影响

目的 :探讨谷氨酰胺 (Gln)对放射损伤动物蛋白质代谢的影响。　方法 :30只Wistar雄性大鼠随机分为对照组、添加Gln照射组 ( Gln组 )、未添加Gln照射组 (-Gln组 )。 Gln组在常规饲料基础上添加 3%Gln ,-Gln组和对照组在常规饲料基础上添加 3%酪蛋白。实验期 2 0天 ,分组喂养至第 15天 , Gln组和 -Gln组大鼠进行60Co γ射线 9.0Gy全身照射。实验结束 ,取血测定血清总蛋白 (TP)、白蛋白 (Alb)、视黄醇结合蛋白 (RBP)、转铁蛋白 (TRF)和前白蛋白 (PA) ;实验期动态测量体重。　结果 :照射前 ,三组动物体重组间无明显差异 ;照射后 , Gln组、-Gln组体重明显低于对照组 (P <0 .0 1) ,-Gln组体重也明显低于 Gln组 (P <0 .0 5 ) ;-Gln组血清TP、Alb、RBP和PA均明显低于对照组 (P <0 .0 5或P <0 .0 1) ,而 Gln组仅血清TP明显低于对照组 (P <0 .0 1)。　结论 :补充Gln可减少放射损伤动物体重的丢失和改善蛋白质营养水平     

不同途径补充谷氨酰胺对大鼠肠粘膜和通透性的影响

目的比较大鼠手术化疗时,普通肠外、肠内营养与补充谷氨酰胺的肠外、肠内营养对肠道功能的影响.方法雄性Wistar大鼠60只,随机分为6组(n=10)Chow 1组,普通饲料加中心静脉插管;PN组,普通肠外营养;PN+G组,肠外营养加谷氨酰胺;Chow 2组,普通饲料加胃造瘘;EN组,普通肠内营养;EN+G组,肠内营养加谷氨酰胺.Chow组给普通饲料,肠外和肠内营养组所给营养液均为等氮2.5 g N@kg-1@d-1、等热卡1 046 kJ@kg-1@d-1(250 kcal@kg-1@d-1),氮热卡比值1100.4组营养支持大鼠在术后第4天,按75 mg@kg-1体重腹腔注射5-Fu.结果(1)体重术后第8天时,以PN组下降最显著(-14.8±7.6)g(P＜0.05);EN组其次(-6.6±2.2)g(P＜0.05);PN+G组略有下降(-1.1±0.2)g,但无统计学差异;EN+G组体重则有所增加(2.7±4.2)g.(2)谷氨酰胺浓度与Chow组比较,PN组和EN组血浆和肌肉的谷氨酰胺浓度显著下降,而PN+G组和EN+G组谷氨酰胺浓度增高.(3)细菌移位PN组和EN组细菌移位阳性率分别为80%和70%(P＜0.05);PN+G组、EN+G组和Chow组分别为30%、30%和20%,3组间比较无显著差异.(4)肠道粘膜通透性与手术后化疗前比较,PN组和EN组的通透性增加(P＜0.05),而PN+G组和EN+G组的通透性变化不大,与Chow组比较无显著性差异.(5)肠粘膜形态术后第8天时,PN组和EN组空肠和结肠粘膜厚度和绒毛高度显著低于Chow组(P＜0.01),PN+G组和EN+G组与Chow组相似,EN+G组的绒毛高度和粘膜厚度优于PN+G组.结论补充谷氨酰胺的肠外、肠内营养与普通肠外、肠内营养比较,可减少肠道通透性增高和细菌移位、减少肠粘膜损伤,并能增加血浆、肌肉和小肠谷氨酰胺水平,肠内营养补充谷氨酰胺对肠道功能的影响优于肠外营养补充谷氨酰胺.     

肠饲谷氨酰胺对烧伤后肠道粘膜结构的保护作用

本研究利用３０％贵州小型香猪烧伤后早期肠道营养模型，在早期肠道营养液中加入谷氨酰胺，观察其对烧伤后肠道粘膜结构的保护作用。结果显示，伤后１０ｄ，单纯早期肠道营养组动物空肠、回肠粘膜的ＤＮＡ、ＲＮＡ和蛋白质含量，以及粘膜厚度、绒毛高度和隐窝深度均明显降...     

谷氨酰胺双肽保护肠粘膜屏障

传统的肠外营养和化疗药应激可导致肠粘膜形态及屏障功能障碍。本文研究腹腔注射５－Ｆｕ后谷氨酰胺双肽对肠粘膜屏障的影响。合格的、符合评定标准的大鼠随机分为两组，胃肠外营养维持７ｄ，第４天腹腔注射５－Ｆｕ。接受传统肠外营养液的为对照组（ｎ＝１０），接受传统...     

谷氨酰胺对缺血再灌注损伤早期小肠粘膜细胞凋亡的影响

目的探讨谷氨酰胺(Gln)对缺血再灌注(I/R)损伤早期小肠粘膜细胞凋亡的影响。方法30只Wistar大鼠被随机分为A～E共5组(每组6只)。采用肠系膜上动脉夹闭法复制小肠I/R(15min/60min)模型。A～D组大鼠分别于缺血前或后经右颈外静脉微泵持续输注肠外营养(PN)或PN+3%Gln(1小时),于复流1小时后取小肠组织备检。E组为空白对照组,不行I/R,输注PN1小时后采取标本。观察各组小肠上皮的形态学改变、原位细胞凋亡、肠粘膜还原型谷胱甘肽(GSH)含量及增殖抗原(PCNA)和Bcl-2的表达。结果缺血前、后输注PN+3%Gln与仅输注TPN各组相比,小肠形态学改变不明显,但粘膜细胞凋亡显著减少(P<0.01),肠粘膜总GSH及GSH含量增加(P<0.05),Bcl-2表达增强,而PCNA表达差异无显著性。结论输注Gln对短暂性I/R损伤所致的小肠粘膜细胞凋亡具有一定预防与治疗作用,其机制可能与提高肠粘膜GSH含量及Bcl-2表达增强有关。     

谷氨酰胺保护严重烧伤病人肠粘膜屏障功能的研究

目的：观察严重烧伤病人肠粘膜屏障功能的变化及口服谷氨酰胺颗粒剂对它的影响。方法：采用随机双盲对照法,将烧伤总面积在30％－60％、三度烧伤面积在10％－30％的39例病人,随机分为谷氨酰胺治疗组（Gln组20例）和安慰剂对照组（C组19例）。Gln组每天服用谷氨酰胺颗粒剂0．5g/kg。C组服用同等剂量的安慰剂,疗程为7天。检测用药前后两组病人血中谷氨酰胺浓度、二胺氧化酶（DAO）活性、内毒素含量及肠粘膜通透性的变化,并记录一般情况和住院日。结果：Gln组病人用药7天后,血中谷氨酰胺含量明显高于C组（P＜0．01）,而血浆DAO活性、内毒素含量及肠粘膜通透性均显著低于C组（P＜0．01）,住院日显著短于C组。结论：服用谷氨酰胺颗粒剂能显著提高严重烧伤病人血中谷氨酰胺水平,减轻伤后肠道受损程度,保护肠粘膜屏障,并有助于缩短住院日。     

口服谷氨酰胺治疗烧伤延迟复苏肠粘膜损害的临床研究

目的 探讨谷氨酰胺(Gln)对烧伤延迟复苏肠粘膜损害的保护作用.方法 将25名延迟复苏的烧伤患者随机分为Gln治疗组(A组,伤后2 d开始服用谷氨酰胺颗粒,12例),非Gln治疗组(B组,不使用Gln治疗,13例),同时设15例非延迟复苏大面积烧伤患者为烧伤对照组(C组),以及正常人对照组(D组,15例),观察伤后1、7、14、21 d血中二胺氧化酶(DAO)、D-乳酸及肿瘤坏死因子(TNFα)含量的变化.结果 伤后一天A、B、C三组DAO、D-乳酸、TNFa明显高于D组(p<0.05),伤后7 d达高峰,A组和B组明显高于C组(p<0.05).A、B、C三组伤后14及21 d上述三种物质浓度下降明显,A组下降幅度大,与B、C两组比较有显著性差异(p<0.05).结论 烧伤延迟复苏明显加重肠粘膜损害,谷氨酰胺对烧伤延迟复苏患者肠粘膜损害有保护作用.     

谷氨酰胺对肠屏障功能保护作用的研究进展

肠道作为一个免疫器官 ,起着阻隔细菌和内毒素的屏障作用 ,而谷氨酰胺对维持肠粘膜上皮功能是必不可少的 ,其对肠粘膜上皮的生长和修复、对免疫功能的改善及抗氧化损伤的作用具有理论意义和临床价值。作者就谷氨酰胺对肠屏障功能的影响及其机制的研究现状作如下综述     

补锌对缺锌大鼠烫伤后肠粘膜上皮细胞增殖的影响

目的 探讨补锌对缺锌大鼠烫伤后肠粘膜上皮细胞增殖的影响。方法 1个月龄大鼠饲予低锌饲料（含锌量：1.6μg/g）1周造成缺锌模型。20%深Ⅱ度烫伤后改饲3种不同含锌饲料（含锌量分别为：16,24.7,286.9644g/g)1周,同时设1组大鼠烫伤前后均饲予正常含锌饲料（含锌量：24.7μg/g）作为对照组,烫伤后第8天处死大鼠,留取标本,在动物处死前6h腹腔注射长春新碱（1mg/kg),诗数肠腺细胞增殖率（CCRP）与标记指数（LI）用以反映肠粘膜增殖情况。结果 各补锌组空肠CCPR,LI均高于缺锌组,回肠也存在类似的趋势,结论 改善锌营养状态有利于烧伤后肠粘膜损伤的修复。     

Cisplatin Upregulates Glutamine Transport in Human Intestinal Epithelial Cells

Background: Glutamine (GLN) prevents the intestinal mucosal injury induced by chemotherapy, although the mechanism of this protective action has not yet been elucidated. Amino acid transport across the plasma membrane is essential for supplying enterocytes with amino acids for cellular metabolism. It was hypothesized that chemotherapy stimulates GLN transport, which enables GLN to be used more efficiently as a metabolic fuel. Methods: A rat model was used to examine the effect of enteral GLN on intestinal mucosal injury induced by intraperitoneal injection of cisplatin (7.0 mg/kg of body weight). The effects of cisplatin on amino acid transport and the expression of messenger RNA and protein were evaluated by real‐time polymerase chain reaction and Western blot analysis, respectively, in the human intestinal epithelial cell line Caco‐2. The effects of cisplatin on glutaminase activity and intracellular glutathione were also studied. Results: GLN prevented mucosal atrophy induced by cisplatin in rats. In Caco‐2 cells, cisplatin significantly increased GLN transport and the expression of GLN transporter ASCT2 messenger RNA and protein. Leucine, but not glutamate, transport significantly increased in the cisplatin‐treated group due to the increase in LAT1 (leucine transporter) protein expression. Glutaminase activity and intracellular glutathione increased significantly in the cisplatin‐treated group. Conclusions: Bolus enteral GLN prevents intestinal mucosal injury induced by cisplatin in rats, as demonstrated by increased GLN transport and increased GLN transporter expression after cisplatin administration.     

术前术中持续输注谷氨酰胺对大鼠肝脏缺血再灌注损伤的影响

目的研究术前术中持续输注谷氨酰胺对大鼠肝脏缺血再灌注损伤的影响。方法 16只雄性Wistar大鼠随机分为实验组与对照组,每组8只,2组均行右侧颈外静脉插管,实验组输入3％丙氨酰-谷氨酰胺二肽(AlaGln),对照组输入生理盐水,连续输注3天,直到缺血再灌注结束。Pringle's法行肝缺血40分钟,再灌注1小时后检测门静脉血中内毒素(ET)、主动脉血中谷丙转氨酶(ALT)、谷草转氨酶(AST)、乳酸脱氢酶(LDH)及肝组织细胞间黏附分子-1(ICAM-1)的表达。结果实验组ET水平(0.3229±0.0756)EU／ml显著高于对照组(0.2021±0.0495)EU／ml(P＜0.01)；实验组ALT水平(407.29±84.27)U／L显著高于对照组(312.67±66.48)U／L,(P＜0.05)；AST、LDH两组比较差异无显著性。实验组肝组织ICAM-1表达较对照组明显增强(P＜0.05)。结论术前术中持续输注谷氨酰胺对大鼠肝脏缺血再灌注损伤可能是有害的。     

静脉应用谷氨酰胺双肽对肠外瘘大鼠肠黏膜结构的影响

目的探讨谷氨酰胺(Gln)的静脉注射制剂L-丙氨酰-L-谷氨酰胺对肠外瘘大鼠的黏膜完整性和黏膜细胞增殖的影响。方法肠外瘘大鼠模型制作成功后分为全胃肠外营养(TPN)组和TPN Gln组,7天后采集大鼠静脉血,利用分光光度法检测血浆Gln含量、改良的酶学分光光度法检测血浆D-乳酸含量、偶氮显色鲎试剂法测定血浆内毒素含量,切取部分小肠作石蜡切片观察黏膜形态,小肠黏膜标本制作细胞悬液利用流式细胞仪检测细胞增殖指数和S期细胞比率。结果TPN组小肠绒毛数量减少,变短变粗,黏膜层及固有层厚度变薄,小肠腺变短变细,成萎缩样变。TPN Gln组与TPN组相比,小肠绒毛形态完整,上皮细胞排列整齐,未见细胞坏死现象,腺体未见萎缩。TPN Gln组大鼠血浆Gln浓度、小肠黏膜的S期细胞比率和增殖指数均较TPN组显著增高(P<0.05);血浆D-乳酸、内毒素浓度较TPN组显著降低(P<0.05)。结论Gln的静脉注射制剂L-丙氨酰-L-谷氨酰胺可以促进肠外瘘大鼠肠黏膜细胞的增殖,恢复肠黏膜屏障,减少内毒素的吸收。     

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。     

Effect of L-Glutamine on Chylomicron Formation and Fat-Induced Activation of Intestinal Mucosal Mast Cells in Sprague-Dawley Rats

Glutamine (Gln) is required for intestinal mucosal homeostasis, and it can promote triglyceride absorption. The intestinal mucosal mast cells (MMCs) are activated during fat absorption. This study investigated the potential role of Gln on fat absorption-induced activation of MMCs in rats. Lymph fistula rats (n = 24) were studied after an overnight recovery with the infusion of saline only, saline plus 85 mM L-glutamine (L-Gln) or 85 mM D-glutamine (D-Gln), respectively. On the test day, rats (n = 8/group) were given an intraduodenal bolus of 20% Intralipid contained either saline only (vehicle group), 85 mM L-Gln (L-Gln group), or 85 mM D-Gln (D-Gln group). Lymph was collected hourly for up to 6 h for analyses. The results showed that intestinal lymph from rats given L-Gln had increased levels of apolipoprotein B (ApoB) and A-I (ApoA-I), concomitant with an increased spectrum of smaller chylomicron particles. Unexpectedly, L-Gln also increased levels of rat mucosal mast cell protease II (RMCPII), as well as histamine and prostaglandin D₂ (PGD₂) in response to dietary lipid. However, these effects were not observed in rats treated with 85 mM of the stereoisomer D-Gln. Our results showed that L-glutamine could specifically activate MMCs to degranulate and release MMC mediators to the lymph during fat absorption. This observation is potentially important clinically since L-glutamine is often used to promote gut health and repair leaky gut.     

Distinct Effects of Growth Hormone and Glutamine on Activation of Intestinal Stem Cells

Background: For patients with short bowel syndrome under parenteral nutrition support, growth hormone (GH) and glutamine (GLN) have been found to help the growth of intestinal mucosa. In this research, we studied the effects of GH and GLN on intestinal stem cells (ISCs). Methods: The in vitro and in vivo effects of GH and/or GLN on ISCs were evaluated by observing the ability of ISCs to form organoids in a Matrigel culture system. The expression levels of stemness and differentiation markers in ISCs and organoids were assessed using quantitative real‐time polymerase chain reaction, immunofluorescence assay, and immunohistochemistry staining. Results: In vitro administration of GH activated the stemness of ISCs, whereas GLN enhanced the expression of chromogranin A and Muc2, which are differentiation markers in enteroendocrine and goblet cells, respectively. Administration of GH or GLN in mice showed that GH, but not GLN, upregulated the proliferative activity of ISCs with increased formation of crypt organoids. In addition, GH increased the expression of Lgr5 and GLN enhanced expression of Muc2 in the crypt fractions of the intestines in mice. Conclusion: These results suggest that GH mainly enhances proliferative activities, whereas GLN promotes the differentiation potential of ISCs.     

肠黏膜血流改变在创伤性脑损伤大鼠肠黏膜屏障应激性变化中的作用

目的探讨肠黏膜血流改变在创伤性脑损伤大鼠肠黏膜屏障应激性变化机制中的作用。方法雄性Wistar大鼠64只，随机分为创伤性脑损伤组和假手术组，2组大鼠分别按术后6、12、24和48小时时相点分为4个亚组（n=8），测定肠黏膜血流量，光镜和透射电镜下观察肠黏膜组织形态学变化。结果创伤性脑损伤组各时相点的肠黏膜血流量均低于假手术组（P〈0．05）；光镜下创伤性脑损伤组肠黏膜上皮细胞受损，电镜下可见肠黏膜细胞间紧密连接较假手术组增宽。结论创伤性脑损伤后早期肠黏膜屏障即已受损，而肠黏膜血流量的下降是导致这一病理生理变化的重要因素之一。     

食物RNA对早期断乳大鼠小肠成熟的影响

目的：通过饲料补充酵母RNA探讨食物RNA对早期断乳大鼠小肠成熟的影响。方法：18日龄早期断乳大鼠阴机分为两组，一组为对照组，供给基础饲料，另一组为RNA补充组，供给添加1％酵母RNA的基础饲料，喂养5天后测定小肠生长成熟有关指标。结果：酵母RNA补充组大鼠体重、肠重量、肠长度，肠粘膜重量与对照组比较无统计学差异，补充RNA对肠碱性磷酸酶、蔗糖酶、乳糖酶和麦芽糖酶等肠成熟的标志酶活性亦未见明显影响。结论：通过食物补充RNA对早期断乳大鼠小肠的生长和成熟未显示有意义的作用。这可能与幼龄大鼠化吸收RNA的酶系尚不健全有关。     

The Prophylactic Effects of Glutamine on Muscle Protein Synthesis and Degradation in Rats with Ethanol-Induced Liver Damage

The purpose of this research was to investigate the prophylactic effects of glutamine on muscle protein synthesis and degradation in rats with ethanol-induced liver injury. For the first 2 weeks, Wistar rats were divided into two groups and fed a control (n = 16) or glutamine-containing diet (n = 24). For the following 6 weeks, rats fed the control diet were further divided into two groups (n = 8 per group) according to whether their diet contained no ethanol (CC) or did contain ethanol (CE). Rats fed the glutamine-containing diet were also further divided into three groups (n = 8 per group), including a GG group (glutamine-containing diet without ethanol), GE group (control diet with ethanol), and GEG group (glutamine-containing diet with ethanol). After 6 weeks, results showed that hepatic fatty change, inflammation, altered liver function, and hyperammonemia had occurred in the CE group, but these were attenuated in the GE and GEG groups. Elevated intestinal permeability and a higher plasma endotoxin level were observed in the CE group, but both were lower in the GE and GEG groups. The level of a protein synthesis marker (p70S6K) was reduced in the CE group but was higher in both the GE and GEG groups. In conclusion, glutamine supplementation might elevate muscle protein synthesis by improving intestinal health and ameliorating liver damage in rats with chronic ethanol intake.