谷氨酰胺对体外循环患者肠道保护作用的临床研究

1、谷氨酰胺对体外循环患者肠道保护作用的临床研究         08-08-31 15:21:00     编辑：studa20              作者：刘小雄，彭金华，徐建军，雷伟程 【摘要】  目的 观察体外循环（extracorporeal circulation,ECC）患者接受谷氨酰胺(glutamine, Gl

2、n)治疗后血清二胺氧化酶(diamine oxidase, DAO )、肿瘤坏死因子(tumor necrotic factor, TNF-)水平的变化，以初步阐明Gln促进ECC患者肠粘膜损伤修复的机制。方法 将24名ECC患者随机分成Gln组(n=12)和对照组(n=12)， Gln组ECC前一周开始口服麦滋林颗粒，剂量为0.50 g/（kg·day），对照组给予安慰剂。两组病例均按常规进行ECC术，分别于术前7天,ECC后2 h,24 h,72 h抽外周静脉血5毫升。生化法检测血清DAO浓度，酶联免疫吸附实验(enzyme linked immunosorbent assay,

3、ELISA)检测血清TNF-浓度。结果 两组患者的血清DAO、TNF-水平在ECC前无统计学意义（P0.05），ECC后升高（P0.05），并于2 h达到峰值,而后下降。DAO于ECC后72h仍然高于术前，TNF-则恢复到术前。Gln组DAO、TNF-在ECC后2 h、24 h均较对照组降低 （P0.05）。结论 ECC可引起患者血清DAO、TNF-升高，提示ECC可导致肠道损伤，Gln可以在一定程度上降低ECC患者血清DAO、 TNF-水平，促进肠粘膜损伤的修复。 【关键词】  体外循环；谷氨酰胺；二胺氧化酶；肿瘤坏死因子；肠粘膜损伤Abstract: OBJECTIVE 

4、;  To observe the changes of plasmic level of diamine oxidase (DAO) and tumor necrotic factor (TNF- ) happened after L-Glutamine (Gln) used orally in the patients undergoing extracorporeal circulation (ECC) and discuss the mechanism of protective effects of Gln on intestinal mucosal injury caus

5、ed by ECC. METHODS  24 patients undergoing ECC were divided randomly into two groups: Gln group(n=12) and control group (n=12).In Gln group,marzutene-s granules (Gln) ( 0.50g/(kg·day) was given for seven days before ECC. While the control group received placebo. Plasmic levels of DAO and T

6、NF- were measured at baseline (seven days  preoperatively) and 2hours,24hours,72hours after ECC.The plasmic concentrations of DAO were detected by biochemical method, of  TNF- by enzyme linked immunosorbent assay (ELISA)  technique. RESULTS  Levels of DAO and TNF- were no signifi

7、cant difference in both group before ECC  (P0.05) and increased significantly at 2hours,24hours after ECC (P0.05) respectively,then decreased. Levels of DAO were higher at 72 hours after ECC than before ECC,while TNF- returned to normal at 72hours after ECC.In Gln group,DAO and TNF- levels were

8、 significantly lower than those in control group at 2hours,24hours after ECC (P0.05) respectively. CONCLUSION  The plasmic concentrations of DAO and TNF- were increased after ECC,which indicated the intestinal mucosal injury happened during ECC, and decreased signifcantly in Gln group compared

9、to control group,which indicated that Gln maybe improved the intestinal mucosal repairing and maintained the intestinal mucosal integrity efficiently in patients undergoing ECC.Key words：  Extracorporeal circulation;Glutamine;Diamine oxidase;Tumor necrotic factor;Intestinal mucosal lnjury在体外循环(

10、extracorporeal circulation，ECC)手术患者中，胃肠道粘膜损伤出现明显临床表现者为0.6%2.0%，亚临床表现高达80%以上，有临床表现者死亡率高达92%941，可见危害的严重性。近年来研究表明，对于烧（创）伤、感染、手术后、放化疗肿瘤患者，补充外源性的谷氨酰胺（glutamine，Gln）有助于肠粘膜的生长和修复作用，减轻炎性反应，其效果已得到了充分肯定2。然而Gln是否能够保护ECC术患者的肠道粘膜仍不清楚。我们通过观察Gln对ECC后血清二胺氧化酶(diamine oxidase，DAO)、肿瘤坏死因子(tumor necrotic factor，TNF-)水平

11、变化的影响，以初步阐明Gln有促进ECC患者肠粘膜的保护作用。1  资料与方法1.1  一般资料  研究对象为2005年8月至2005年11月期间24例行心脏停跳ECC手术患者，其中二尖瓣置换术9例、主动脉瓣置换术5例、双瓣置换术1例、房间隔缺损修补术4例、室间隔缺损修补术5例。所有患者心功能为-级，均无肝肾功能障碍、无长期应用糖皮质激素史、无炎性和(或)代谢性疾病史及凝血功能异常。术前将24例患者随机分成试验组(Gln组 n=12)和对照组(Con组 n=12)；两组患者临床资料见表1。1.2  手术及给药方法  两组患者均采用静脉加吸入复合

12、全身麻醉。术前用药为东莨菪碱、杜冷丁。咪唑安定、维库溴胺、芬太尼快速诱导气管插管，麻醉机机械通气，根据麻醉深浅用芬太尼，维库溴胺或吸入异氟烷维持麻醉深度；同时建立各种检测系统。ECC采用Jostra心肺机、西京希健I型膜肺，中度血液稀释（Hct 0.20.30），术中维持鼻咽温度26.931.2，灌注流量2.02.5 L/（min·m2），平均动脉压维持在5080 mmHg，心肌保护采用顺行性灌注41冷血心脏停搏液。肝素（3mg/kg）抗凝，检测ACT，ECC期间维持ACT480 s，停机后常规给予0.71的鱼精蛋白中和肝素。    Gln组采用日本寿制药株式会社生产的麦滋林颗粒(本剂1g中含有谷氨酰胺0.99 g，鹤山市广增医药有限公司提供)于术前一周开始服用,剂量为0.50g/（kg·day），每日分3次口服。对照组温开水替代麦滋林颗粒。1.3  标本采集和检测  两组病例分别于术前7天（口服麦滋林前）、停止ECC后2 h、24 h、72 h分别抽外周静脉血5 ml，立即以3000 r/min离心20 min,取血清置于-70冰箱保存待检。    血清DAO浓度采用改良分光光度法测定，试剂盒由美