切换至 "中华医学电子期刊资源库"

中华妇幼临床医学杂志(电子版) ›› 2009, Vol. 05 ›› Issue (03) : 207 -213. doi: 10.3877/cma.j.issn.1673-5250.2009.03.102

论著

谷氨酰胺双肽对接受造血干细胞移植患儿肠道保护作用的临床研究
翁文骏, 方建培, 陈纯, 周敦华, 黄科, 郭海霞, 薜红漫, 黎阳   
  1. 510120 广州,中山大学附属第二医院(孙逸仙纪念医院)儿科
  • 出版日期:2009-06-01

Effects of N(2)-L-alanyl-L-glutamine on Intestine in Children Underwent Hematopoietic Stem Cell Transplantation.

Wen-jun WENG, Jian-pei FANG, Chun CHEN, Dun-hua ZHOU, Ke HUANG, Hai-xia GUO, Hong-man XUE, Yang LI   

  1. Department of Pediatrics, Second Affiliated Hospital, Sun Yat-Sen University, Guangzhou 510120, China
  • Published:2009-06-01
  • Supported by:
    * Project No.30872382, supported by the National Natural Science Foundation of China
引用本文:

翁文骏, 方建培, 陈纯, 周敦华, 黄科, 郭海霞, 薜红漫, 黎阳. 谷氨酰胺双肽对接受造血干细胞移植患儿肠道保护作用的临床研究[J/OL]. 中华妇幼临床医学杂志(电子版), 2009, 05(03): 207-213.

Wen-jun WENG, Jian-pei FANG, Chun CHEN, Dun-hua ZHOU, Ke HUANG, Hai-xia GUO, Hong-man XUE, Yang LI. Effects of N(2)-L-alanyl-L-glutamine on Intestine in Children Underwent Hematopoietic Stem Cell Transplantation.[J/OL]. Chinese Journal of Obstetrics & Gynecology and Pediatrics(Electronic Edition), 2009, 05(03): 207-213.

目的

研究谷氨酰胺双肽[N(2)–L–alanyl–L–glutamine;dipeptide grutamine; dipeptiven,DPT]对造血干细胞移植(hematopoietic stem cell transplantation,HSCT)患儿并发症及恢复的影响。

方法

选取2004年3月至2007年11月,在中山大学附属第二医院儿科接受造血干细胞移植的56例患儿为研究对象,将其按疾病种类作分层抽样分为谷氨酰胺双肽组(DPT组,n=28)和对照组(n=28)(本研究遵循的程序符合本院人体试验委员会所制定的伦理学标准,得到该委员会批准,分组征得受试患儿监护人的知情同意,并与其签署临床研究知情同意书)。DPT组患儿除接受全胃肠外营养(total parenteral nutrition;TPN)支持外,每天给予谷氨酰胺双肽,剂量为1.5 mL/(kg·d),共计21 d。对照组采用不含谷氨酰胺(glutamine,Gln)的全胃肠外营养支持。检测DPT组和对照组应用谷氨酰胺双肽前1天、第7、第14、第21天患儿体重、肝功生化、血常规,并对造血干细胞植入和移植后30 d内并发症发生情况进行分析。

结果

DPT组发生肠炎为12例,对照组为26例,两组比较,DPT组发生率低于对照组,且差异有显著意义(P<0.05)。DPT组患儿的腹泻、腹痛、呕吐、口腔溃疡持续时间,腹泻、腹痛、呕吐次数均短于或少于对照组,两组比较,差异有显著意义(P<0.05)。两组患儿发生鹅口疮、肛裂等持续时间比较,DPT组短于对照组,且差异无显著意义(P<0.05)。DPT组患儿长期发热(≥14 d)为2例,对照组为10例,两组比较,DPT组的发热总持续时间、最长持续发热时间短于对照组,平均每天最高体温低于对照组,且差异有显著意义(P<0.05)。DPT组患儿发生口腔溃疡为14例、鹅口疮为4例、肛裂为3例、血真菌培养呈阳性为0例、血细菌培养呈阳性为6例,而对照组分别为19例、5例、1例、1例和7例,两组比较,差异无显著意义(P>0.05)。DPT组患儿静脉应用抗生素时间为(20.0±7.1) d、入无菌层流室治疗时间为(20.2±6.7) d,对照组分别为(25.4±6.4) d和(24.1±6.9) d,两组比较,差异有显著意义(P<0.05)。DPT组造血干细胞植入成功为22例,对照组为21例;DPT组发生肠道急性移植物抗宿主病(acute graft versus host disease,aGVHD)为3例、肝静脉闭塞病(venous occlusive disease, COD)为0例,对照组分别为5例和1例,两组移植成功率和肠道急性移植物抗宿主病、肝静脉闭塞病发生率方面比较,差异无显著意义(P>0.05)。DPT组白细胞(white blood cell,WBC)植入时间为(15.3±5.1) d,血小板(platelet,PLT)植入时间为(29.0±14.4) d,对照组分别为(16.2±5.8) d和(32.5±18.6) d,两组比较,差异无显著意义(P>0.05)。两组在DPT组患儿应用谷氨酰胺双肽的第7、第14、第21天的天冬氨酸转氨酶(aspartate aminotransferase,AST),丙氨酸转氨酶(alanine aminotransferase,ALT),血尿素氮(blood urea nitrogen,BUN),肌酐(creatinine,Cr)、葡萄糖(glucose,Glu)、总蛋白(total protein, TP)、白蛋白(albumin, ALB)、球蛋白(globulin, GLB)、白细胞、红细胞(red blood cell, RBC)、血小板、血红蛋白(hemoglobin, Hb)比较,差异无显著意义(P>0.05)。在应用谷氨酰胺双肽的第7、第14、第21天,DPT组患儿的体重下降幅度与对照组相应指标比较,下降幅度较少,差异有显著意义(P<0.05);且于第21天,DPT组患儿平均体重已恢复至造血干细胞移植前水平,而对照组尚未恢复。

结论

谷氨酰胺双肽对造血重建恢复无影响,但能改善造血干细胞移植患儿的营养状态,减少黏膜炎、肠炎的发生率及症状持续时间,减少长期发热发生率及发热持续时间,缩短抗生素治疗时间及无菌层流室治疗时间,同时不增加肠道急性移植物抗宿主疾病。

Objective

To investigate effects of N(2)-L-alanyl-L-glutamine(dipeptide grutamine; dipeptiven, DPT)on complications and recovery of pediatric patients with hematopoietic stem cell transplantation(HSCT).

Methods

From March 2004 to November 2007, 56 pediatric patients with hematopoietic stem cell transplantation were assigned to receive either N(2)-L-alanyl-L-glutamine supplemented total parenteral nutrition (TPN) (DPT group, n=28) or standard total parenteral nutrition (control group, n=28) by means of stratified sampling of disease classification. The patients in DPT group received total parenteral nutrition enriched by 1.5 mL/(kg·d)N(2)-L-alanyl-L-glutamine injected for 21 days, and control group received glutamine-free total parenteral nutrition. Clinical chemistry index, blood cell count, body weight, complication and recovery of patients with hematopoietic stem cell transplantation were monitored and evaluated in all patients before and after total parenteral nutrition.

Results

12 patients of DPT group and 26 patients of control group developed infantile diarrhea (P<0.05). Duration of diarrhea, abdominal pain, vomiting and oral ulceration, frequencies of diarrhea, abdominal pain and vomiting were longer in control group than those of DPT group (P<0.05). However, no significant difference was found in time length of oral candidiasis and anal fissure between two groups (P>0.05). Two patients of DPT group and ten cases of control group developed long term fever(≥14 days) (P<0.05). Time length of fever, frequencies of fever and the highest temperature were longer, much more and higher in control group than those of DPT group (P<0.05). There were 14, 4, 3 patients in DPT group and 19, 5, 1 patients in control group developed oral ulceration, oral candidiasis, anal fissure (P>0.05). There were no significant difference between two groups in bacterial and fungi culture positive patients (P>0.05). Time length of antibiotic requirements and free-germ ward stay were shortened in DPT group [(20.0±7.1) d vs. (25.4±6.4) d, (20.2±6.7) d vs. (24.1±6.9) d; P<0.05]. The time to reach >0.5×109/L neutrophils and the time to reach >20×109/L platelets(PLT)were (15.3±5.1) d, (29.0±14.4) d in DPT group and (16.2±5.8) d, (32.5±18.6) d in control group (P>0.05). There were 22 patients in DPT group and 21 patients in control group were successfully engrafted (P>0.05). There were 3, 0 patients in DPT group and 5, 1 patients in control group developed acute intestinal graft versus host disease(aGVHD), veno-occlusive disease (P>0.05). No significant difference were found in clinical chemistry index and blood cell count between two groups (P>0.05). Loss of body weight in DPT group was less than that of control group after hematopoietic stem cell transplantation (P<0.05).

Conclusion

There is no difference in the time to neutrophil engraftment between two groups. Pediatric patients with hematopoietic stem cell transplantation will benefit from N(2)-L-alanyl-L-glutamine-supplemented total parenteral nutrition for the nutritional status improving, diminishing the incidence of mucositis, infantile diarrhea and long term fever, reducing the time of fever, free-ward stay and antibiotic requirements, and the incidence of acute intestinal graft versus host disease not increased.

1 Bierings M, Nachman JB, Zwaan CM. Stem cell transplantation in pediatric leukemia and myelodysplasia: State of the art and current challenges. Curr Stem Cell Res Ther, 2007, 2(1):53–63.
2 Krishnamurti L, Abel S, Maiers M, et al. Availability of unrelated donors for hematopoietic stem cell transplantation for hemoglobinopathies. Bone Marrow Transplant, 2003, 31(7):547–550.
3 Schrier SL, Angelucci E. New strategies in the treatment of the thalassemias. Annu Rev Med, 2005, 56:157–171.
4 Ho VT, Revta C, Richardson PG. Hepatic veno–occlusive disease after hematopoietic stem cell transplantation:Update on defibrotide and other current investigational therapies. Bone Marrow Transplant,2008, 41(3):229–237.
5 da Fonseca MA, Hong C. An overview of chronic oral graft–vs–host disease following pediatric hematopoietic stem cell transplantation. Pediatr Dent, 2008, 30(2):98–104.
6 Kato K, Khaled Y, Mineishi S. Reduced–intensity stem cell transplantation for hematological malignancies:Current status and the future. Curr Stem Cell Res Ther, 2007, 2(2):149–162.
7 Luo M, Bazargan N, Griffith DP, et al. Metabolic effects of enteral versus parenteral alanyl–glutamine dipeptide administration in critically ill patients receiving enteral feeding:A pilot study. Clin Nutr, 2008, 27(2):297–306.
8 Fuentes–Orozco C, Cervantes–Guevara G, Mucino–Hernández I, et al. L–alanyl–L–glutamine–supplemented parenteral nutrition decreases infectious morbidity rate in patients with severe acute pancreatitis. JPEN J Parenter Enteral Nutr, 2008, 32(4):403–411.
9 Duska F, Fric M, Waldauf P, et al. Frequent intravenous pulses of growth hormone together with glutamine supplementation in prolonged critical illness after multiple trauma:Effects on nitrogen balance, insulin resistance, and substrate oxidation. Crit Care Med, 2008, 36(6):1707–1713.
10 Bunpo P, Murray B, Cundiff J, et al. Alanyl–glutamine consumption modifies the suppressive effect of L–asparaginase on lymphocyte populations in mice. J Nutr, 2008, 138(2):338–343.
11 Savy GK. Glutamine supplementation. Heal the gut, help the patient. J Infus Nurs, 2002, 25(1):65–69.
12 Mertes N, Schulzki C, Goeters C, et al. Cost containment through L– alanyl– L–glutamine supplemented total parenteral nutrition after major abdominal surgery:A prospective randomized double–blind controlled study. Clin Nutr, 2000, 19(6):395–401.
13 Déchelotte P, Hasselmann M, Cynober L, et al. L–alanyl–L–glutamine dipeptide–supplemented total parenteral nutrition reduces infectious complications and glucose intolerance in critically ill patients: The French controlled, randomized, double–blind, multicenter study. Crit Care Med, 2006, 34(3):598–604.
14 Satoh J, Tsujikawa T, Fujiyama Y, et al. Enteral alanyl–glutamine supplement promotes intestinal adaptation in rats. Int J Mol Med, 2003, 12(4):615–620.
15 Schmucker DL.Intestinal mucosal immunosenescence in rats. Exp Gerontol, 2002, 37(2–3):197–203.
16 Braga–Neto MB, Warren CA, Oriá RB, et al. Alanyl–glutamine and glutamine supplementation improves 5–fluorouracil–induced intestinal epithelium damage in vitro. Dig Dis Sci, 2008, 53(10):2687–2696.
17 Luo M, Fernandez–Estivariz C, Jones DP, et al. Depletion of plasma antioxidants in surgical intensive care unit patients requiring parenteral feeding:Effects of parenteral nutrition with or without alanyl–glutamine dipeptide supplementation. Nutrition, 2008, 24(1):37–44.
18 Lima NL, Soares AM, Mota RM, et al. Wasting and intestinal barrier function in children taking alanyl–glutamine–supplemented enteral formula. J Pediatr Gastroenterol Nutr, 2007, 44(3):365–374.
19 Wu K, Wang BX, Wang XP. The protective effect of glutamine on intestinal immune function in acute nerotizing pancreatitis in rat. Chin J Gastroenterol Hepat, 2001, 10:39–41.[吴恺,王冰娴,王兴鹏. 谷氨酰胺对急性坏死性胰腺炎大鼠肠道黏膜局部免疫功能的保护作用. 胃肠病学和肝病学杂志,2001, 10:39–41.]
20 Carneiro BA, Fujii J, Brito GA, et al. Caspase and bid involvement in Clostridium difficile toxin A–induced apoptosis and modulation of toxin A effects by glutamine and alanyl–glutamine in vivo and in vitro. Infect Immun, 2006,74(1):81–87.
21 Zhang X, Wang WZ, Li MB, et al. Effects of dipeptiven enriched parenteral nutrition on bacterial translocation and mucosa membrane structure of the transplanted small intestine in rats. J Fourth Military Med Univ, 2002, 23:1989–1992.[张溪,王为忠,李孟彬,等.力肽强化肠外营养对小肠移植大鼠肠黏膜结构及肠道细菌移位的影响. 第四军医大学学报,2002, 23:1989–1992.]
22 Ockenga J, Borchert K, Stüber E, et al. Glutamine–enriched total parenteral nutrition in patients with inflammatory bowel disease. Eur J Clin Nutr, 2005, 59(11):1302–1309.
23 Brito GA, Carneiro–Filho B, Oriá RB, et al. Clostridium difficile toxin A induces intestinal epithelial cell apoptosis and damage: Role of Gln and Ala–Gln in toxin A effects. Dig Dis Sci, 2005, 50(7):1271–1278.
24 Kudsk KA, Wu Y, Fukatsu K, et al. Glutamine–enriched total parenteral nutrition maintains intestinal interleukin–4 and mucosal immunoglobulin A levels. JPEN J Parenter Enteral Nutr, 2000, 24:270–275.
25 Wan XY, Bi LY, Zhang YL. Protective effect of glutamine on rats with pseudomonas pneumonia. Chin J Inten Med, 2006, 45(12):1004–1007.[万献尧,毕丽岩,张永利. 谷氨酰胺对铜绿假单胞菌所致肺部感染大鼠的防护作用. 中华内科杂志,2006, 45(12):1004–1007.]
26 Zhang XQ, Li JS, Shi X, et al. Experimental study of effects of glutamine–enriched TPN on acute rejection of small bowel transplantation. J Shandong Univ, 2001, 39:531–536.[张小桥,黎介寿,施鑫,等. 谷氨酰胺强化TPN对小肠移植急性排斥反应影响的实验研究. 山东医科大学学报,2001, 39:531–536.]
27 Zhou HS, Hu JM, Zhang DH, et al. Effects of glutamine supplementation on Th1/Th2 cytokines level in patients undergoing hematopoietic stem cell transplantation. Chin J Clin Nutrit, 2006, 14(6):365–368.[周红升,胡金梅,张东华,等. 谷氨酰胺双肽对造血干细胞移植后患者血清Th1/Th2类细胞因子水平的影响. 中国临床营养杂志,2006, 14(6):365–368.]
28 Mapara MY, Leng C, Kim YM, et al. Expression of chemokines in GVHD target organs is influenced by conditioning and genetic factors and amplified by GVHR. Biol Blood Marrow Transplant, 2006, 12(6):623–634.
29 Johansson JE, Ekman T. Gut toxicity during hemopoietic stem cell transplantation may predict acute graft–versus–host disease severity in patients. Dig Dis Sci, 2007, 52(9):2340–2345.
30 Stelljes M, Hermann S, Albring J, et al. Clinical molecular imaging in intestinal graft–versus–host disease:Mapping of disease activity, prediction, and monitoring of treatment efficiency by positron emission tomography. Blood, 2008, 111(5):2909–2018.
[1] 陶宏宇, 叶菁菁, 俞劲, 杨秀珍, 钱晶晶, 徐彬, 徐玮泽, 舒强. 右心声学造影在儿童右向左分流相关疾病中的评估价值[J/OL]. 中华医学超声杂志(电子版), 2024, 21(10): 959-965.
[2] 何甘霖, 陈香侬, 李萍, 甄佳怡, 李京霞, 邹外一, 许多荣. 白血病异基因造血干细胞移植术后股骨坏死的影响因素[J/OL]. 中华关节外科杂志(电子版), 2024, 18(04): 450-456.
[3] 刘琴, 刘瀚旻, 谢亮. 基质金属蛋白酶在儿童哮喘发生机制中作用的研究现状[J/OL]. 中华妇幼临床医学杂志(电子版), 2024, 20(05): 564-568.
[4] 向韵, 卢游, 杨凡. 全氟及多氟烷基化合物暴露与儿童肥胖症相关性研究现状[J/OL]. 中华妇幼临床医学杂志(电子版), 2024, 20(05): 569-574.
[5] 刘静, 王燕妮, 王继萍. 儿童毛发移植应用前景及病例讨论[J/OL]. 中华损伤与修复杂志(电子版), 2024, 19(04): 368-368.
[6] 郑宝英, 黄小兰, 贾楠, 朱春梅. 儿童难治性肺炎支原体肺炎早期预警指标[J/OL]. 中华实验和临床感染病杂志(电子版), 2024, 18(04): 215-221.
[7] 刘冉佳, 崔向丽, 周效竹, 曲伟, 朱志军. 儿童肝移植受者健康相关生存质量评价的荟萃分析[J/OL]. 中华移植杂志(电子版), 2024, 18(05): 302-309.
[8] 刘云, 时月, 郭冬梅, 邱志远, 王丽娟, 冉学红, 李乾鹏. 造血干细胞移植治疗伴有胚系突变的髓系肿瘤患者三例并文献复习[J/OL]. 中华移植杂志(电子版), 2024, 18(04): 230-234.
[9] 丁荷蓓, 王珣, 陈为国. 七氟烷吸入麻醉与异丙酚静脉麻醉在儿童腹股沟斜疝手术中的应用比较[J/OL]. 中华疝和腹壁外科杂志(电子版), 2024, 18(05): 570-574.
[10] 中华医学会器官移植学分会, 中华医学会外科学分会外科手术学学组, 中华医学会外科学分会移植学组, 华南劈离式肝移植联盟. 劈离式供肝儿童肝移植中国临床操作指南[J/OL]. 中华肝脏外科手术学电子杂志, 2024, 13(05): 593-601.
[11] 刘军, 丘文静, 孙方昊, 李松盈, 易述红, 傅斌生, 杨扬, 罗慧. 在体与离体劈离式肝移植在儿童肝移植中的应用比较[J/OL]. 中华肝脏外科手术学电子杂志, 2024, 13(05): 688-693.
[12] 张琛, 秦鸣, 董娟, 陈玉龙. 超声检查对儿童肠扭转缺血性改变的诊断价值[J/OL]. 中华消化病与影像杂志(电子版), 2024, 14(06): 565-568.
[13] 王晓瑜, 郭群英, 牛雅萌, 赵成松. 公立儿童医院促进儿科就医均等化实践探析[J/OL]. 中华临床医师杂志(电子版), 2024, 18(04): 383-387.
[14] 陈晓胜, 何佳, 刘方, 吴蕊, 杨海涛, 樊晓寒. 直立倾斜试验诱发31 秒心脏停搏的植入心脏起搏器儿童一例并文献复习[J/OL]. 中华脑血管病杂志(电子版), 2024, 18(05): 488-494.
[15] 曹亚丽, 高雨萌, 张英谦, 李博, 杜军保, 金红芳. 儿童坐位不耐受的临床进展[J/OL]. 中华脑血管病杂志(电子版), 2024, 18(05): 510-515.
阅读次数
全文


摘要