手术前开始应用生长激素对肠外营养病人蛋白质代谢、肌肉功能、肠粘膜屏障和细胞免疫功能的影响
作者：刘卫 蒋朱明 于健春 王秀荣 舒红 崔巍
单位：北京协和医院外科
关键词：
中国临床营养杂志000117摘 要：生长激素(GH)在术后应用已有报告，其代谢效应在术后3～4天出现，为探索创伤后分解代谢的进一步改善，术前开始应用重组人生长激素(rHGH)。目前国内外均无术前应用rHGH的报告。 目的(1)观察手术前3天开始应用rHGH治疗能否使以往研究中于术后第4天出现的正氮平衡在术后提早出现，并观察其对术后肌肉功能的影响。(2)观察手术前后应用rHGH对肠外营养病人肠粘膜通透性、小肠粘膜形态及细胞免疫功能的影响。 方法本研究为前瞻性、随机、双盲、安慰剂对照的临床研究。20例因胃肠道疾病行手术治疗的病人随机进入研究组或对照组。术前3天至术后第7天，研究组病人接受rHGH(0.3IU.kg-1.d-1，皮下注射)治疗，对照组接受安慰剂。从术前1天至术后第6天，两组病人接受等氮等热卡的肠外营养(20Kcal·kg-1.d-1，0.15gN·kg-1·d-1)。观察指标包括：术后6天的氮平衡，手术前后体重、双手握力、行走速度、血浆谷氨酰胺水平、肠粘膜通透性、外周血淋巴细胞亚群、血常规和肝、肾功能变化及小肠粘膜形态。 结果1.研究组术后6天累积氮平衡明显好于对照组(P<0.01)，并于术后第2天开始出现持续的正氮平衡，而对照组术后6天持续为负氮平衡。2.对照组病人术后体重、双手握力和行走速度均较术前下降(P<0.05)，研究组病人术后无明显下降(P>0.05)，两组变化差值比较有显著性差异(P<0.05)。3.rHGH治疗显著提高了研究组病人血浆GH和IGF-1浓度(P<0.01)，而对照组血浆GH和IGF-1浓度较术前无变化(P>0.05)。4.对照组病人术后血浆谷氨酰胺水平较术前下降(P<0.05)，研究组病人术后维持术前水平(P>0.05)。5.对照组病人术后CD淋巴细胞比例及CD/CD淋巴细胞比值较术前下降(P<0.05)，研究组术后无明显变化(P>0.05)，两组间变化差值比较有显著性差异(P<0.05)。6.手术后对照组肠粘膜通透性较术前明显升高(P<0.05)，研究组升高不明显(P>0.05)。研究组小肠粘膜厚度和绒毛高度与对照组比较无显著性差异(P>0.05)。7.rHGH治疗后研究组空腹血糖较治疗前有升高趋势，但与对照组比较无显著性差异。rHGH治疗对血常规和肝肾功能未见明显影响。8.临床未见与rHGH治疗有关的严重副反应。 结论1.手术前开始应用rHGH，结合低氮低热卡肠外营养治疗可有效地纠正手术应激引起的分解代谢，合成代谢作用较术后应用提前出现。rHGH治疗维持肌肉功能。2.rHGH减轻手术应激和肠外营养引起的肠粘膜通透性增高，保护肠屏障功能。3.rHGH治疗防止手术应激引起的细胞免疫功能抑制，保护机体免疫功能。
, 百拇医药
The impact of preoperative treatment of recombinant human growth hormone on protein metabolism, muscle function, intestinal barrier function and cell immune function
LIU Wei ,JIANG Zhuming ,YU Jianchun
(PUMC Hospital, Beijing)
Abstract：Objective 1. To determine if the positive nitrogen balance could be achieved in early postoperative period by the pretreatment of rHGH. 2. To evaluate the effects of rHGH on intestinal permeability, intestinal morphology and cell immune function. Methods A placebo-controlled randomized double-blind trial were performed. 20 patients undergoing abdominal surgery were randomized into two groups. The patients in the study group received rHGH (0.3IU/kg/day) subcutaneously from the 3rd day before operation onward to the 7th day after operation. The patients in the control group received placebo. All the patients were given isonitrogenic (0.15g N/kg/day) and isocaloric (20Kcal/kg/day) parenteral nutrition from the 1st preoperative day to the 6th postoperative day. The Nitrogen balance and cumulative nitrogen balance were calculated during the 6 postoperative days. The body weight, hands grip strength, and the time requested to walk 20 meters were evaluated, the plasma glutamine level, peripheral CD /CD lymphocyte proportion, blood routine and biochemistry analysis, intestinal permeability were determined before and after rHGH treatment. A jejunum biopsy was performed on the operation day for the determination of the intestinal morphology. Results 1) The positive nitrogen balance was achieved from the 2nd postoperative day onward with the pretreatment of rHGH, whereas the negative nitrogen balance lasted during the postoperative 6 days in the control group. The cumulative nitrogen balance in the study group was significantly better than that in the control group (P<0.01). 2) In the control group, body weigh, hands grip strength decreased,and the time requested to walk 20 meters increased significantly compared to the preoperative level ( P<0.05). In the study group, there were no significant changes on the 7the postoperative day ( P<0.05). The changes between the two groups were significantly different(P<0.05). 3) GH and IGF-I levels were similar in the two groups and had not significantly changed in the control group by the 7th postoperative day. In the study group a significant increase in serum levels of GH and IGF-I was observed on the 3rd and the 7th postoperative day. 4) The plasma glutamine level in control group decreased on POD + 7 compared to preoperative level (P<0.05), and the level of glutamine in the study group did not change ( P<0.05).5) A significant decrease in CD subset proportion and CD /CD ratio was observed in the control group on the 7th postoperative day, whereas no change was observed in study group.6) The intestinal permeability (L/M) in the control group was elevated on POD + 7 (P<0.05), whereas the L/M ratio in the study group kept the same as preoperative. 7) Glucose level in the control group was unaltered, but in the study group a trend of rise in glucose level was observed, which was not significant. 8)No adverse reaction related with rHGH was observed. Conclusions 1 )rHGH combined with parenteral nutrition could overcome the protein catabolic effects of the stress response, and maintain the muscle function. 2)rHGH prevented the increase of intestinal permeability, preserved intestinal barrier function. 3)rHGH eliminated the depression in cellular immunity following the surgical stress., 百拇医药
单位：北京协和医院外科
关键词：
中国临床营养杂志000117摘 要：生长激素(GH)在术后应用已有报告，其代谢效应在术后3～4天出现，为探索创伤后分解代谢的进一步改善，术前开始应用重组人生长激素(rHGH)。目前国内外均无术前应用rHGH的报告。 目的(1)观察手术前3天开始应用rHGH治疗能否使以往研究中于术后第4天出现的正氮平衡在术后提早出现，并观察其对术后肌肉功能的影响。(2)观察手术前后应用rHGH对肠外营养病人肠粘膜通透性、小肠粘膜形态及细胞免疫功能的影响。 方法本研究为前瞻性、随机、双盲、安慰剂对照的临床研究。20例因胃肠道疾病行手术治疗的病人随机进入研究组或对照组。术前3天至术后第7天，研究组病人接受rHGH(0.3IU.kg-1.d-1，皮下注射)治疗，对照组接受安慰剂。从术前1天至术后第6天，两组病人接受等氮等热卡的肠外营养(20Kcal·kg-1.d-1，0.15gN·kg-1·d-1)。观察指标包括：术后6天的氮平衡，手术前后体重、双手握力、行走速度、血浆谷氨酰胺水平、肠粘膜通透性、外周血淋巴细胞亚群、血常规和肝、肾功能变化及小肠粘膜形态。 结果1.研究组术后6天累积氮平衡明显好于对照组(P<0.01)，并于术后第2天开始出现持续的正氮平衡，而对照组术后6天持续为负氮平衡。2.对照组病人术后体重、双手握力和行走速度均较术前下降(P<0.05)，研究组病人术后无明显下降(P>0.05)，两组变化差值比较有显著性差异(P<0.05)。3.rHGH治疗显著提高了研究组病人血浆GH和IGF-1浓度(P<0.01)，而对照组血浆GH和IGF-1浓度较术前无变化(P>0.05)。4.对照组病人术后血浆谷氨酰胺水平较术前下降(P<0.05)，研究组病人术后维持术前水平(P>0.05)。5.对照组病人术后CD淋巴细胞比例及CD/CD淋巴细胞比值较术前下降(P<0.05)，研究组术后无明显变化(P>0.05)，两组间变化差值比较有显著性差异(P<0.05)。6.手术后对照组肠粘膜通透性较术前明显升高(P<0.05)，研究组升高不明显(P>0.05)。研究组小肠粘膜厚度和绒毛高度与对照组比较无显著性差异(P>0.05)。7.rHGH治疗后研究组空腹血糖较治疗前有升高趋势，但与对照组比较无显著性差异。rHGH治疗对血常规和肝肾功能未见明显影响。8.临床未见与rHGH治疗有关的严重副反应。 结论1.手术前开始应用rHGH，结合低氮低热卡肠外营养治疗可有效地纠正手术应激引起的分解代谢，合成代谢作用较术后应用提前出现。rHGH治疗维持肌肉功能。2.rHGH减轻手术应激和肠外营养引起的肠粘膜通透性增高，保护肠屏障功能。3.rHGH治疗防止手术应激引起的细胞免疫功能抑制，保护机体免疫功能。
, 百拇医药
The impact of preoperative treatment of recombinant human growth hormone on protein metabolism, muscle function, intestinal barrier function and cell immune function
LIU Wei ,JIANG Zhuming ,YU Jianchun
(PUMC Hospital, Beijing)
Abstract：Objective 1. To determine if the positive nitrogen balance could be achieved in early postoperative period by the pretreatment of rHGH. 2. To evaluate the effects of rHGH on intestinal permeability, intestinal morphology and cell immune function. Methods A placebo-controlled randomized double-blind trial were performed. 20 patients undergoing abdominal surgery were randomized into two groups. The patients in the study group received rHGH (0.3IU/kg/day) subcutaneously from the 3rd day before operation onward to the 7th day after operation. The patients in the control group received placebo. All the patients were given isonitrogenic (0.15g N/kg/day) and isocaloric (20Kcal/kg/day) parenteral nutrition from the 1st preoperative day to the 6th postoperative day. The Nitrogen balance and cumulative nitrogen balance were calculated during the 6 postoperative days. The body weight, hands grip strength, and the time requested to walk 20 meters were evaluated, the plasma glutamine level, peripheral CD /CD lymphocyte proportion, blood routine and biochemistry analysis, intestinal permeability were determined before and after rHGH treatment. A jejunum biopsy was performed on the operation day for the determination of the intestinal morphology. Results 1) The positive nitrogen balance was achieved from the 2nd postoperative day onward with the pretreatment of rHGH, whereas the negative nitrogen balance lasted during the postoperative 6 days in the control group. The cumulative nitrogen balance in the study group was significantly better than that in the control group (P<0.01). 2) In the control group, body weigh, hands grip strength decreased,and the time requested to walk 20 meters increased significantly compared to the preoperative level ( P<0.05). In the study group, there were no significant changes on the 7the postoperative day ( P<0.05). The changes between the two groups were significantly different(P<0.05). 3) GH and IGF-I levels were similar in the two groups and had not significantly changed in the control group by the 7th postoperative day. In the study group a significant increase in serum levels of GH and IGF-I was observed on the 3rd and the 7th postoperative day. 4) The plasma glutamine level in control group decreased on POD + 7 compared to preoperative level (P<0.05), and the level of glutamine in the study group did not change ( P<0.05).5) A significant decrease in CD subset proportion and CD /CD ratio was observed in the control group on the 7th postoperative day, whereas no change was observed in study group.6) The intestinal permeability (L/M) in the control group was elevated on POD + 7 (P<0.05), whereas the L/M ratio in the study group kept the same as preoperative. 7) Glucose level in the control group was unaltered, but in the study group a trend of rise in glucose level was observed, which was not significant. 8)No adverse reaction related with rHGH was observed. Conclusions 1 )rHGH combined with parenteral nutrition could overcome the protein catabolic effects of the stress response, and maintain the muscle function. 2)rHGH prevented the increase of intestinal permeability, preserved intestinal barrier function. 3)rHGH eliminated the depression in cellular immunity following the surgical stress., 百拇医药