谷胺酰胺双肽保护小儿HSCT肠道外器官功能的临床研究

Protective effect of N(2)-L-alanyl-L-glutamine on the extra-intestine in pediatric patients with HSCT

【目的】观察谷氨酰胺双肽[N（2）-L-alanyl—L-glutamine；dipeptide glutamine，DPT）保护接受造血干细胞移植（hematopoietic stem cell transplantation，HSCT）患儿肠道外器官功能的临床疗效。【方法】2004年3月～2007年11月，将56例拟接受HSCT的患儿按疾病种类作分层抽样分为两组：谷氨酰胺双肽使用组（DPT组，n=28）和对照组（n=28）。DPT组患儿除接受标准胃肠外营养支持外，每天给予谷氨酰胺（glutamine，Gln），剂量为1．5mL／（kg·d），共计21d。对照组采用不含Gln的标准化静脉营养支持。检测应用DPT前1d、第7、14、21d患儿体重、肝功生化、血常规，并分析造血干细胞植入和移植后30d内并发症发生情况。【结果】DPT组的呼吸道感染、泌尿道感染、长期发热（≥14d）发生率、咽痛咳嗽时间、尿频尿痛时间、发热总时间、最长连续发热时间、平均每天最高体温、静脉应用抗生素时间、入无菌层流房时间、体重下降幅度低于或少于对照组，差异有显著性（P〈0．05）；植入率、皮肤急性移植物抗宿主病（acute graft versus host disease，aGVHD）、肠道aGVHD、肝静脉闭塞病和出血性膀胱炎发生率、WBC植入时间、PLT植入时间、浓缩红细胞、血小板、注射用重组人IL-11、粒细胞集落刺激因子的输注次数及需要量，DPT应用第7d、第14d、第21d的肝功、血常规检测各项指标两组相比差异无显著性（P〉0．05）。【结论】DPT对造血重建或aGVHD无影响；但能改善HSCT状态，减少粘膜炎、呼吸道感染、泌尿道感染的发生率及症状持续时间，减少长期发热发生率及发热时间，缩短抗生素治疗时间及住无菌层流房时间。

[Objective] To investigate the effect of N（2）-L-alanyl-L-glutamine （dipeptide glutamine,DPT） on complication and recovery of pediatric patients with hematopoietic stem cell transplantation （HSCT）. [ Methods] From March 2004 to November 2007,56 pediatric patients with HSCT were randomly assigned to receive either DPT supplemented total parenteral nutrition （TPN） （the DPT group, n = 28） or standard total parenteral nutrition （the control group, n = 28）. The patients in DPT group received total parenteral nutrition enriched by 1.5 mL/（kg · d ）DPT injection for 21 days, and the 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] The incidence of respiratory infection, urinary tract infection and long term fever（≥14 days）, time length of pharyngalgia and cough, time length of odynuria and thamuria, time length of fever, frequencies of fever, the highest temperature, loss of body weights, time length of antibiotic requirements and free-germ ward stay were longer, much more and higher in the control group than those in the DPT group （P〈0.05）. No significant difference was found in the time to reach 〉0.5 × 10^9/L neutrophils and the time to reach 〉20 × 10^9/L platelets, the incidence of acute dermatic graft-versus-host-disease（GVHD）, acute intestinal GVHD, veno occlusive disease and hemorrhagic cystitis,clinical chemistry index , blood cell count, infusion frequency and fluence of concentrate erythrocyte, blood platelet, IL-11 and G-CSF between these two group （P〉0.05）. [Conclusions] Pediatric patients with HSCT will benefit from DPT-supplemented TPN for the nutritional status improving, diminishing the incidence of mucositis, respiratory infection and urinary tract infection and long term fever, reducing time length of fever, free-ward stay and antibiotic requirements, and the incidence of acute dermatic GVHD and acute intestinal GVHD not increased.