重组人生长激素对腹腔感染后低白蛋白血症的防治作用——实验与临床研究

本研究旨在探讨重组人生长激素 ( rh GH)对腹腔感染引起的低白蛋白血症的治疗作用。分别在体外实验、动物实验和临床研究中 ,观察 rh GH对白蛋白 m RNA表达和白蛋白合成的影响。结果示 rh GH明显促进体外培养肝细胞白蛋白基因表达 ;在内毒素损伤的肝细胞模型中 ,rh GH能显著减轻内毒素介导的白蛋白 m RNA表达抑制。在体内 ,rh GH明显促进正常大鼠和腹腔感染大鼠肝脏白蛋白 m RNA表达。在 TPN的基础上 ,rh GH明显提高腹腔感染病人白蛋白、前白蛋白、转铁蛋白血清浓度。因此 ,rh GH对腹腔感染引起的低白蛋白血症有显著的防治作用。     

重组人生长激素对肠外瘘病人小肠黏膜增殖及营养状况的影响

目的:研究重组人生长激素(rhGH)对非肿瘤肠外瘘病人营养状况及小肠黏膜上皮细胞增生的影响.方法:选择8例唇状小肠外瘘病人,人院次日以1.5 REE热量行肠内营养,待7天氮平衡稳定后,每天皮下注射GH 10U,连用7天.分别于GH使用前1天、给予GH后第4、7天经瘘口活检肠黏膜,行常规病理及增殖细胞核抗原(PC-NA)检测,同时行机体组成分析、检测病人血清蛋白质等营养指标和氮平衡测定.结果:肠外瘘病人给予GH后第4、7天黏膜的绒毛高度与使用GH前1天相比有明显增加(P＜0.01).小肠黏膜细胞中PCNA表达第4、7天与使用GH前1天相比均有非常显著增加(P＜0.01).第7天与使用GH第4天相比明显增加(P＜0.05).使用GH后可使病人体重增加.病人血清清蛋白、前清蛋白、转铁蛋白、纤维连接蛋白均较使用前有明显增加.同时还能维持机体的正氮平衡.结论:应用GH能明显促进肠外瘘病人小肠黏膜增生,促进蛋白质合成,维持机体正氮平衡.     

重组人生长激素治疗腹腔感染后低白蛋白血症的实验与临床研究

探讨重组人生长激素 (rh GH)对腹腔感染引起的低白蛋白血症的治疗作用。分别在体外实验、动物实验和临床研究中 ,观察 rh GH对白蛋白 m RNA表达和白蛋白合成的影响。结果 :rh GH明显促进体外培养肝细胞白蛋白基因表达 ;在内毒素损伤的肝细胞模型中 ,rh GH显著减轻内毒素介导的白蛋白 m RNA表达抑制 ;在体内 ,rh GH明显促进正常大鼠和腹腔感染大鼠肝白蛋白 m RNA表达 ;并明显提高腹腔感染病人血清白蛋白、前白蛋白、转铁蛋白浓度。结果提示 ,rh GH对腹腔感染引起的低白蛋白血症有明显的防治作用。重组人生长激素治疗腹腔感染后低白…     

低热量PN联合rhGH在严重腹腔感染病人的应用

目的：探讨低热量肠外营养和重组人生长激素联合应用对严重腹腔感染病人的作用。方法：我院从１９９６年８月至１９９８年１２月，对４０例严重腹腔感染伴低蛋白血症的病人、采用低热量ＰＮ，配合短程小剂量ｒｈＧＨ进行营养治疗，监测体重，血清白蛋白，转铁蛋白，肝酐身高指数，总淋巴细胞计数和计算氮平衡，并进行治疗前，后自身对照观察。     

低热量肠外营养加生长激素对严重应激和重度营养不良病人的治疗体会

目的：观察生长激素加强危重病人应用全肠外营养支持的效果。方法：对严重应激（７例）和重度营养不良（９例）共１６例病人采用低热量肠外营养加重组生长激素联合治疗，并与仅用ＴＰＮ治疗的同类病人作对照研究，治疗后分别测定体重、血清白蛋白，前白蛋白和转铁蛋白及免疫球蛋白，计算氮平衡，观察精神状态。结果：治疗组比对照组在氮平衡、前白蛋白和转铁蛋白有明显改善（Ｐ＜０．０１），血清白蛋白，免疫球蛋白亦有明显增高（Ｐ＜０．０５），精神状态普遍较好，获得了较好的临床疗效。结论：低热量肠外营养加重组生长激素联合治疗是机体病理状态下一种较为理想的营养支持方法     

亮氨酸改善盲肠结扎穿孔小鼠生长激素抵抗

目的:探讨盲肠结扎穿孔小鼠生长激素-胰岛素样生长因子-1(GH-IGF-1)轴的变化及亮氨酸的干预作用. 方法:将40只小鼠随机分为四组,每组10只.即正常对照组(Control组)、假手术组(Sham组)、盲肠结扎穿孔等渗盐水组(CLP-N组)和盲肠结扎穿孔亮氨酸组(CLP-L组).采用盲肠结扎穿孔法制作腹腔感染模型后,CLP-N组给予等渗盐水灌胃,CLP-L组给予亮氨酸灌胃,连续7d.第8天腹腔麻醉后取门静脉血,检测小鼠血清生长激素(GH)和胰岛素样生长因子-1(IGF-1)水平.同时测定小鼠肝组织生长激素受体(GHR)、IGF-1、胰岛素样生长因子结合蛋白-1(IGFBP-1)和胰岛素样生长因子结合蛋白-3(IGFBP-3)mRNA表达量. 结果:与Control组比,CLP-N组小鼠血清GH水平明显升高(P＜0.01)、而血清IGF-1水平急剧下降(P＜0.01),并且伴随着肝组织GHR和IGFBP-3 mRNA水平显著降低(P＜0.01)以及IGFBP-1 mRNA水平明显升高(P＜0.01);而CLP-L组小鼠血清GH水平明显升高(P＜0.01)、血清IGF-1水平轻微下降(P＜0.05)以及肝组织GHR、IGFBP-1和IGFBP-3 mRNA水平明显升高(P＜0.01). 结论:盲肠结扎穿孔小鼠存在获得性GH抵抗,亮氨酸可改善此现象.     

低热量肠内营养联合生长激素在胃肠道肿瘤患者术后的应用

目的探讨低热量肠内营养联合重组人生长激素(rhGH)对胃肠道肿瘤患者术后蛋白质代谢的影响及其治疗效果。方法将2003年1月～2005年7月在我科行胃肠道肿瘤根治术的40例患者随机分成两组:低热量肠内营养支持 安慰剂为对照组(n=20);低热量肠内营养支持 rhGH为研究组(n=20)。rhGh在术后第3天开始应用,连续应用7天。观察患者术后蛋白质代谢和血清胰岛素样生长因子-1(IGF-1)的变化情况。结果研究组术后第5天恢复正氮平衡。两组血清白蛋白、前白蛋白、转铁蛋白、纤维连接蛋白、IGF-1在术后第3天均显著下降,治疗后有不同程度的恢复。研究组术后第10天前白蛋白、转铁蛋白、纤维连接蛋白和IGF-1显著高于对照组(P<0.05)。结论低热量肠内营养支持联合rhGH能促进胃肠道肿瘤患者术后的蛋白质合成,改善患者营养状况。     

生长激素对门静脉高压症病人肝蛋白质合成的影响

目的:了解生长激素(GH)对经颈静脉肝内门体分流术(TIPS)后门脉性肝硬化病人肝蛋白质代谢的影响. 方法:对10例门静脉高压症病人,在TIPS术后第2天开始皮下注射重组人生长激素(rhGH)8 U×7天.检测治疗前及治疗后3、7天血清清蛋白(Alb)、前清蛋白(PA)、纤维连接蛋白(FN)水平,同时测定血清胰岛素样生长因子(IGF-1)水平,进行治疗前后的比较. 结果:血清IGF-1水平TIPS术前与术后比较无显著差异,GH治疗后3天明显升高(P<0.01);Alb水平TIPS术前与GH治疗后3天比较无显著差异,7天后明显升高(P<0.05);PA和FN水平在GH治疗后第3天开始升高,第7天明显升高 (P<0.01). 结论:GH可以促进肝硬化门静脉高压症病人肝蛋白质合成.     

小剂量重组人生长激素对腹腔脓毒症病人疾病严重度的影响

目的:观察腹腔脓毒症病人应用小剂量生长激素(GH)后疾病严重度的变化,评估GH对脓毒症病人病情和预后的影响,从而评价GH在脓毒症病人中应用的安全性.方法:18例非肿瘤、既往无代谢性疾病史的腹腔脓毒症病人,在进行外科引流并且血流动力学平稳后进入8天的研究,第1天为基准阶段,其后每天给予重组人生长激素(rhGH)10 U,肌内注射,检测每天的血清GH、IGF-1和IGFBP-3的浓度,应用APACHE-Ⅱ评分系统和Elebute＆Stoner的脓毒症评分系统,每天进行疾病严重度的评估.结果:应用rhGH后,血清GH、IGF-1和IGFBP-3的浓度均有明显升高,疾病严重度的评分均有明显下降.结论:rhGH在腹腔脓毒症病人中应用可以发挥其生物学效应;腹腔脓毒症病人在行病灶清除引流,生命体征平稳后应用rhGH是安全的.脓毒症病人的疾病严重度评分并未增加,脓毒症评分在用药期间明显减小.     

低热量肠外营养联合生长激素在胃肠道肿瘤病人术后应用的临床研究

目的:探讨重组人生长激素(rhGH)对胃肠道肿瘤病人术后蛋白质代谢的影响.方法:将39例胃肠道肿瘤病人随机、双盲分为两组:低热量肠外营养支持 安慰剂为对照组(n=20);低热量肠外营养支持 rhGH为治疗组(n=19).观察病人术后血清胰岛素样生长因子(IGF-1)和蛋白质代谢的变化情况.结果:IGF-1、前清蛋白、转铁蛋白、纤维连接蛋白术后3 d均有明显下降,治疗后都有不同程度的恢复.治疗组术后10 d IGF-1、前清蛋白、转铁蛋白、纤维连接蛋白明显高于对照组(P＜0.05);治疗组正氮平衡也比对照组恢复得早(P＜0.05).结论:低热量肠外营养支持联合rhGH能促进胃肠道肿瘤病人的蛋白质合成,明显改善病人术后的营养状况.     

Growth hormone regulation of follicular growth

The somatotropic axis-consisting of growth hormone (GH), the insulin-like growth factors 1 and 2 (IGF1 and IGF2), GH binding protein (GHBP), IGF binding proteins (IGFBPs) 1 to 6, and the cell-surface receptors for GH and the IGFs-has major effects on growth, lactation and reproduction. The primary target tissues for GH are involved in growth and metabolism. The functionality of the somatotropic axis depends in part on the expression of liver GH receptor (GHR), which determines the amount of IGF1 released from the liver in response to GH. The IGF1 acts as a pleiotropic growth factor and also serves as the endocrine negative feedback signal controlling pituitary GH secretion. Growth hormone and IGF1 undergo dynamic changes throughout the life cycle, particularly when animals are either growing, early post partum or lactating. Cells within the reproductive tract can respond directly to GH but to a lesser degree than the primary target tissues. The major impact that GH has on reproduction, therefore, may be secondary to its systemic effects on metabolism (including insulin sensitivity) or secondary to the capacity for GH to control IGF1 secretion. Insulin-like growth factor 1 and IGFBP are also synthesised within the ovary and this local synthesis is a component of the collective IGF1 action on the follicle. Future studies of GH should focus on its direct effects on the follicle as well as its indirect effects mediated by shifts in nutrient metabolism, insulin sensitivity, IGF1 and IGFBP.     

谷氨酰胺和生长激素对术后病人肌肉代谢的影响

目的许多研究表明,给予生长激素和谷氨酰胺能减少手术后肌肉蛋白的分解(术后肌蛋白分解表现在肌蛋白合成减少、谷氨酰胺水平降低和氮丢失增加)。本研究目的是联合使用生长激素和胰岛素样生长因子((IGF-I,一种能解释生长激素部分作用效果的生长因子)及添加生长激素和谷氨酰胺对术后肌肉代谢的影响。     

创伤及感染时GH-IGF-IGFBP轴的变化及其临床意义

创伤和感染病人往往存在高分解代谢,包括蛋白质合成减少、分解增加,形成明显的负氮平衡.如何逆转高分解反应曾经过漫长的探索.除了营养支持外,人们希望通过抗分解激素减轻甚至是逆转高分解状态.新近研究提示,在基础和应激条件下,生长激素-胰岛素样生长因子-胰岛素样生长因子结合蛋白(GH-IGF-IGFBP)轴对调节肌肉蛋白质代谢起着核心作用.该文作者就其在创伤及感染时的变化及其临床意义作一综述.     

支链氨基酸对创伤后代谢影响的研究

目的:观察应用支链氨基酸对手术创伤病人机体代谢的影响. 方法:采用前瞻、随机、单盲、平行、对照、多中心试验设计,选择行腹部外科手术后成年病人120例,随机分为两组:对照组(n=60)应用10.4% 18种复方氨基酸注射液,研究组(n=60)应用10.3%支链氨基酸注射液.采用全营养混合液方式行周围或中心静脉输注,等氮等热量.从术后第2天开始,应用6天.在手术前1天和术后第7天,对所有病人收集空腹血标本检测,同时进行24 h尿液收集作氮平衡分析. 结果:研究组与对照组之间在研究前、后累积氮平衡无明显差异,但在营养液输注第5天,研究组氮平衡显著高于对照组(P<0.01).两组之间研究前、后血清总蛋白、前清蛋白、纤维连接蛋白、转铁蛋白和体重变化无显著差异.两组研究前、后血清清蛋白浓度均降低,但对照组下降更为明显(P<0.05).研究组应用氨基酸后,缬氨酸浓度升高明显,与对照组相比差异显著(P<0.05).缬氨酸、丙氨酸和支链氨基酸浓度较输注前明显升高(P<0.05). 结论:对手术创伤应激病人的肠外营养支持中,应用含较高支链氨基酸的营养液较平衡氨基酸注射液可能更为有效.     

Enterotrophic effect of insulin-like growth factor-I but not growth hormone and localized expression of insulin-like growth factor-I, insulin-like growth factor binding protein-3 and -5 mRNAs in jejunum of parenterally fed rats

BACKGROUND: Administration of insulin-like growth factor (IGF)-I, but not growth hormone (GH), stimulates mucosal hyperplasia in surgically stressed rats with intestinal atrophy induced by hypocaloric total parenteral nutrition (TPN). Our aim was to characterize the basis for this disparity in enterotrophic action by assessing the relationships between stimulation of intestinal growth, nutritional adequacy, and localization of expression of IGF-I, insulin-like growth factor binding protein (IGFBP)-3 and IGFBP-5 mRNAs in jejunum. METHODS: Rats were maintained with TPN for 8 days and treated with IGF-I or GH and adequate nutrition for 5 days after recovery from surgery. Jejunal mass, morphology, and sucrase activity were assessed. Localization of expression of IGF-I, IGFBP-3, and IGFBP-5 mRNAs in jejunum was accomplished by in situ hybridization. RESULTS: Serum IGF-I and body weight gain were significantly increased by IGF-I or GH. Jejunal mucosal dry mass, morphology, and sucrase activity were improved with IGF-I but not GH. There were no differences in IGF-I mRNA. IGFBP-3 mRNA was localized in the lamina propria of the villi. IGF-I or GH stimulated IGFBP-3 expression. IGF-I strongly stimulated IGFBP-5 expression in the lamina propria and the muscularis and induced a twofold increase in IGFBP-5 mRNA based on RNase protection assay of intact jejunum total RNA. GH induced a modest increase in IGFBP-5 expression in the muscularis with no effect on intact jejunum total RNA. CONCLUSIONS: The GH resistance observed in the jejunal mucosa of TPN rats cannot be fully explained by inadequate nutrition. The expression of IGFBP-5 in the lamina propria suggests it may modulate the enterotrophic action of exogeneous IGF-I.     

Combination of recombinant human growth hormone and glutamine-enriched total parenteral nutrition to surgical patients: effects on circulating amino acids

BACKGROUND & AIMS: Both recombinant human growth hormone (rhGH) and glutamine (GLN) may have beneficial anabolic actions on amino acid metabolism. The aim of this study was to evaluate the additive effects of rhGH and GLN on plasma amino acids postoperatively. METHODS: 31 females undergoing laparoscopic cholecystectomy were randomized to three groups: Group I (n=10) received 13 IU/m(2) of rhGH the morning of surgery and the following three postoperative days, together with glutamine-free TPN for the first two postoperative days. Group II (n=11) received rhGH as the first group, together with glutamine-enriched (7 g GLN/m(2)/day) TPN. Group III (n=10) received glutamine-enriched TPN as the second group, but rhGH was replaced by placebo. Daily plasma amino acid concentrations and nitrogen balance were determined. RESULTS: In the GH treated groups, the plasma concentrations of several amino acids were decreased on the third postoperative day, compared to preoperatively. This was not observed in Group III. The changes were more pronounced in Group II. In Group II the negative AV-differences of amino acids tended to be attenuated, while the patients in Group III had increased negative AV-differences. The cumulative nitrogen balance was significantly improved in the GH groups, compared with Group III. CONCLUSION: The combined treatment of growth hormone and glutamine has additive effects on AV-balances of amino acids postoperatively, whereas nitrogen balance is not further improved when adding glutamine to rhGH treatment.     

重症患者肠内营养及生长激素治疗的疗效观察

目的 探讨早期肠内营养(EN)和生长激素(GH)对危重病患者救治的效果.方法 70例危重患者随机分为EN组和EN+GH组.两组营养支持均等热量、等氮量.分别于营养支持前后检测血生化、营养状态指标及肠道黏膜通透性.营养支持治疗10 d后测定两组的免疫学指标与T细胞亚群.营养支持期间每天测定氮平衡,并计算累计氮平衡.结果 EN+GH组体重、白蛋白、转铁蛋白水平的改善优于EN组,但差异无显著性(P＞0.05),而EN+GH组前白蛋白、纤维连接蛋白显著高于EN组(P＜0.05).EN+GH组IgA水平显著低于EN组,而CD4、NK水平显著高于EN组(P＜0.05).EN+GH组肠道通透性显著低于EN组(P＜0.05).EN+GH组累计氮平衡为正氮平衡,而EN组为负氮平衡,二者之间差异具有显著性(P＜0.05).结论 早期EN支持能迅速改善危重患者营养状态,减少并发症,适量应用GH能增强免疫功能,降低致残率和死亡率.     

Nutritional and hormonal effects of biosynthetic human growth hormone in surgical patients on total parenteral nutrition.

The anabolic effects of biosynthetic human growth hormone (BHGH) were tested on 30 patients, aged 37-68 yr, divided into four groups: group 1 received surgery plus total parenteral nutrition (TPN) plus BHGH, group 2 received just surgery and TPN, Group 3 received TPN and BHGH, and group 4 received just TPN. TPN was given as an all-in-one formula (glucose 4.7 g.kg.-1day-1, amino acids 1.2 g.kg-1.day-1, lipids 0.7 g.kg-1.day-1, electrolytes and trace elements. BHGH (0.25 IU.kg-1.day-1) or placebo were administered subcutaneously at 0800 for 10 days. Nitrogen and phosphorous balance, as well as the common plasma nutritional markers (transferrin, albumin, prealbumin), triglycerides, apolipoprotein B, insulin, and cortisol were evaluated daily. Urinary creatinine loss was evaluated on days 3, 7, and 10. Cumulative nitrogen balance was better in group 1 (-16.1 +/- 3.2 g N2) than in group 2 (-33.7 +/- 4.6 g N2) (P less than 0.01), whereas the difference was nonsignificant in groups 3 and 4. Phosphorous balance and creatinine excretion paralleled nitrogen balance. Plasma markers were not significantly improved in group 1 compared with group 2; however, they were significantly better in group 3 than in group 4. Lipids were better metabolized in the BHGH-treated groups. Insulin was increased in both groups 1 and 3, whereas cortisol did not rise after surgical stress, probably because of BHGH administration. A positive effect of BHGH on nutritional status and hormonal background is suggested by these data.     

生长激素强化肠内营养对术后蛋白质代谢的影响

目的 :　了解重组人生长激素 (GH)强化低能量肠内营养 (EN)对心脏手术后病人蛋白质代谢的影响。方法 :　对 3 6例心脏手术后病人随机分成 GH强化 EN治疗组 (试验组 )与单纯EN治疗组 (对照组 )。治疗在术后持续 7天。检测术前、术后第 1、4、8d血浆白蛋白 (A)、转铁蛋白(TF)、前白蛋白 (PA)、视黄醇结合蛋白 (RBP)及术后第 1、2、3、5、7d的氮平衡 (NB) ,并进行组内及组间比较。结果 :　术前两组病人血浆 A、TF、PA、RBP水平无显著差异。术后第 1 d两组病人血浆 A、TF、PA、RBP均较低 ,仅 RBP试验组高于对照组 ;术后第 4、8d血浆 TF、PA、RBP试验组明显高于对照组 ,术后第 8d血浆 A试验组明显高于对照组 ,及术后第 1、2、3、5、7d NB改善试验组明显好于对照组。结论 :　心脏手术后使用重组人 GH强化 EN能在较短时间内提高血浆 A、TF、PA、RBP的水平 ,纠正病人负 NB,改善病人营养状况