围术期生长激素和谷氨酰胺强化的肠内营养对原发性肝癌患者术后营养状况和免疫功能影响的初步研究

Evaluation of growth hormone combined with glutamine-enhanced enteral nutritional on status and immune function of postoperative patients with primary liver cancer during perioperative period

目的探讨围术期生长激素和谷氨酰胺强化的肠内营养对原发性肝癌患者术后营养状况和免疫功能的影响。方法将知情同意的原发性肝癌患者48例,随机分为术前谷氨酰胺强化肠内营养组(术前GEEN组)、术后谷氨酰胺强化肠内营养组(术后GEEN组)、胃肠外营养组。术后GEEN组患者在术后12 h间断口服温水,如患者无明显不适,术后24 h开始口服肠内营养液逐渐增加至全量,第4天开始按30 mL/(kg·d)口服至第七天,术后3 d内,不足的能量或水、电解质通过静脉途径补充。同时术后7 d内按4 IU/d皮下注射基因重组人类生长激素(思增)。术前GEEN组在术前3 d按30 mL/(kg·d)开始口服肠内营养液,术后4 d与术后GEEN组的前4 d方案相同,肛门排气后逐渐恢复饮食。同时术前3 d至术后4 d皮下注射基因重组人类生长激素(思增)。胃肠外营养组术后7 d内按胃肠外营养常规支持,肛门排气后逐渐恢复饮食。观察患者临床恢复情况,记录术后并发症(包括伤口感染或脂肪液化、肺部感染等)。营养前或术前1 d和术后8 d清晨采血检测肝功能、NK细胞、T细胞亚群(CD3比例和CD4/CD8比值)、免疫球蛋白(IgM、IgG、IgA)、补体(C3、C5)。结果术前GEEN组和术后GEEN组中各有1例因术后出现明显腹胀不愿意继续口服而退出,其余个别病例出现轻度腹胀等不适,经过调整进食速度和短暂休息后好转,均按计划完成治疗。三组患者在整个研究过程中均无大出血、手术死亡等严重并发症。三组患者发生感染并发症情况比较,术前GEEN组相对较低,但组间差异无统计学意义(P>0.05)。营养支持后三组患者蛋白水平比较,术后GEEN组、术前GEEN组总蛋白均比胃肠外营养组高(P=0.00),以术前GEEN组提高更明显(P=0.00),而白蛋白水平无明显变化(P=0.16),肠内营养组需要补充的白蛋白量明显少于对照组(P=0.02)。三组患者营养前T细胞、免疫球蛋白等指标无差异(P>0.05)。营养后,术后GEEN组、术前GEEN组CD3比例、CD4/CD8比值均较胃肠外营养组明显升高(P<0.05),NK细胞水平提高不明显(P>0.05)。在体液免疫方面,术后第八天,术后GEEN组和术前GEEN组的IgM、IgG、IgA、C3、C4接近或已经恢复营养前水平(P>0.05),但胃肠外营养组多数指标尚未恢复术前水平,尤其是IgM和IgG,还处于较低水平(P<0.05)。营养支持后,术后GEEN组和术前GEEN组总胆红素和转氨酶都有所降低,而胃肠外营养组却有所升高,但这种变化无统计学意义(P>0.05)。结论对于原发性肝癌患者,围术期应用生长激素和谷氨酰胺强化的肠内营养方法安全、可行,有效改善机体的营养状况,提高免疫功能。

Objective To investigate the influence of glutamine-enhanced enteral nutritional（GEEN） combined with growth hormone on postoperative nutritional status and immune function in patients with primary liver cancer during perioperative period. Methods 48 patients with primary liver cancer were randomly divided into 3 groups： preoperative glutamine-enhanced enteral nutrition group（preoperative GEEN group）, postoperative glutamine-enhanced enteral nutrition group（postoperative GEEN group）, and parenteral nutrition group. Patients in the postoperative GEEN group were given warm water at 12h after operation and were increased enteral nutrition gradually to the normal level at 24h after operation if no obvious discomfort complained. The patients in postoperative GEEN group were fed enteral nutrition （30mL/kg. d） from d4 -7 after operation and the lack of energy supplemented with energy or water, electrolyte within 3 days after operation. The patients in postoperative GEEN group were injected ecombinant human growth hormone（ rhGH ,4IU/d） from dl - 7 days after operation, The common diet was restored gradually after annal exhaust, The patients in the preoperative GEEN group received enteral nutrition before operation for 3 days ,30 mL/（ kg·d）and had the same nutritional scheme as the patients in postoperative GEEN from dl -4 days after operation, The preoperative GEEN group received rhGH injection for 7 days range from preoperative 3 day to postoperative 4d. Patients in the parenteral nutrition group was supported by parenteral nutrition and taken normal diet when gastrointestinal function reeoverying. The clinical recovering and postoperative complication were observed （including wound infections or fat liquefaction, pulmonary infection）. Hepatic function, NK ceils, CD4 ＋ T and CD8·T ceils, IgM , IgA and IgG levels, complement C3 and C5 levels were measured on the 8th day after operation and on the 1 st day before operation. Results Two cases were exited due to complaining to postoperative abdominal distension with 1 cases in the preoperative GEEN group and postoperative GEEN group respectively. The patients in 3 groups had no serious complications such as bleeding, operation death. The occurrence of infection was no significant difference （ P 〉 0. 05 ） among 3 groups, with fewer rate in preoperative GEEN group. After nutritional support, The level of total protein in both preoperative GEEN group and postoperative GEEN group were higher than that in the parenteral nutrition group（P = 0.00）, preoperative GEEN group with higher content obviously （P = 0.00）, No significant changes could be found in albumin levels among the 3 groups （P = 0.16）, but complement albumin in the GEEN groups was lower than that in the parenteral nutrition group （ P = 0.02）. Before nutritional support, the T cells, immunoglobulin among the 3 groups showed no significant difference （P 〉 0.05 ）, but the percentage of CD3 and the radio of CD3/CD4 were higher than that in the parenteral nutrition group （P 〈 0.05） after nutritional support, less change in the level of NK cell among the 3 groups （ P 〉 0.05）. In humoral immunity, The levels of IgM, IgA and IgG, C3 and C5 in both preoperative GEEN group and postoperative GEEN group were close to or had been restored to the levels before GEEN support on the eighth days after surgery （P 〉 0.05 ）, but most indexes of immunity have not yet recovered to the, preoperative level in the parenteral nutrition group , especially the levels of IgM and IgG, were still at the low level（P 〈0.05）. After nutritional support, the levels of preoperative total bilirubin and transaminase were decreased in both preoperative GEEN group and postoperative GEEN group, and were increased in the parenteral nutrition group, but there was no significant difference among the 3 groups. Conclusion Growth hormone combined with glutamine-enhanced enteral nutritional could improve the nutritional status and the immune function , is safe and feasible for the patients with primary liver cancer during perioperative period.