维持性血液透析患者ghrein和leptin血浆水平的研究
摘要
目的
研究维持性血液透析患者生长激素释放肽(ghrelin)、瘦素(leptin)的血浆水平。探讨影响它们血浆水平的因素,揭示它们的分泌失调是否与这些患者的食欲缺乏、营养不良、微炎症、胰岛素抵抗代谢综合征有关。进一步了解它们在这些患者中的调节作用。为治疗这些患者相关并发症开拓新的领域。
方法
采用酶联免疫吸附测试法测量30个维持性血液透析患者和15个对照的健康者总的ghrelin、leptin血浆水平。并测量透析组患者营养状况、微炎症、胰岛素抵抗代谢综合征相关的体格检查和血生化指标。通过改良主观营养评估和食欲调查问卷对透析组患者进行营养状况和食欲评估。比较透析组和对照组,透析组中食欲正常A组与食欲缺乏B组、体重指数小于20组和大于20组、营养正常组和营养不良组之间总的ghrelin、leptin血浆水平及它们比值的均数差别。并探讨总的ghrelin、leptin的血浆水平及它们的比值分别与年龄及营养状况、微炎症、代谢综合征相关标志物的关联。
结果
与对照组相比,透析组空腹总的ghrelin血浆水平、总的ghrelin与leptin血浆水平的比值均数显著高于对照组,而leptin的血浆水平均数没有显著的差别。在透析组中,食欲正常A组的leptin的血浆水平均数显著高于食欲缺乏B组,而总的ghrelin的血浆水平均数显著低于食欲缺乏组,体重指数小于20和大于20组、营养正常和营养不良组之间总的ghrelin、leptin血浆水平及它们比值的均数差别无显著统计意义。在透析组中,空腹leptin血浆水平与肱三头肌皮褶厚度成显著正相关,而与体重、上臂肌围、小腿围成显著负相关。总的ghrelin与leptin血浆水平的比值与血清C反应蛋白(CRP)、改良主观营养评估(SGA)评分成显著正相关,而与血清白蛋白、肱三头肌皮褶厚度成负相关。总的ghrelin血浆水平、血清白蛋白分别与年龄成负相关,而CRP和总的ghrelin与leptin血浆水平的比值分别与年龄成正相关。血清白蛋白又与CRP成负相关。
结论
维持性血液透析患者总的ghrelin血浆水平和总的ghrelin与leptin血浆水平的比值都显著高于对照组。透析组患者发生食欲缺乏、营养不良、微炎症与ghrelin、leptin的分泌失调有关。Ghrelin在发生食欲缺乏、营养不良、微炎症的状况下可能存在负反馈的分泌增加作用,而同时leptin存在负反馈的减少作用。进一步明确ghrelin、leptin在维持性血液透析患者中分泌失调的机制对解决营养不良-微炎症-动脉粥样硬化综合症的难题的研究指出新的方向。ghrelin在老年性患者分泌代偿不足可能是导致他们容易发生食欲缺乏、营养不良、微炎症的因素之一。ghrelin作为一种新药治疗这些患者发生食欲缺乏、营养不良、心血管疾病带来新的展望。
Objective
The aim of study is to investigate the fasting plasma total ghrelin and leptin levels in hemodialysis patients. The factors that affect their plasma levels are also explored. We like to reveal whether their levels are abnormal in these patients with anorexia, malnutrition, micro-inflammation, insulin resistance related metabolic syndrome. We want further to understand their regulatory role in these patients and open up new areas for the treatment of these patients related complications.
Methods
The levels of fasting total ghrelin and leptin were measured by ELISA in 30 hemodialysis patients and 15 normal controls. We also measured the medical examination and blood biochemical markers about nutritional status﹑micro-inflammation﹑metabolic syndrome in dialysis patients. The nutritional and appetite status of dialysis patients were assessed by the modified quantitative subjective gloval assessment(SGA) nutrition and subjective appetite questionnaire. We compared the plasma total ghrelin﹑leptin levels and their ratio between dialysis and control group, normal appetite dialysis groups A and groups B with anorexia, body mass index (BIM)<20 dialysis groups and BIM>20 groups, nutrition normal dialysis groups and the malnourished groups. We also explored the correlations between the plasma total ghrelin﹑leptin levels,their ratio and age, selected nutritional﹑inflammation﹑metabolic syndrome markers respectively.
Results
The fasting plasma toal ghrelin levels and the ratio betwee plasmsa ghrelin and leptin levels in dialysis groups were higher than that in controls.However,there was no difference in the fasting plasma leptin levels between them. In the dialysis groups, the fasting plasma leptin levels were significantly higher in the normal appetite group A than that in the anorexia group B, while the total plasma ghrelin levels lower than the anorexia group B.There were no significant differences in the fasting plasma toal ghrelin﹑leptin levels and their ratio between the BIM<20 and>20 groups, the normal nutrition and unnutrition groups(by SGA) respectively in dialysis groups. The fasting plasma leptin levels was positively correlated with body weigh﹑triceps skinfold(TSF),and negatively with midarm muscle circumference(MAC)﹑calf circumference in dialysis patients. The ghrelin-leptin ratio was positively correlated with serum C-reactive protein(CRP)﹑the modified quantitative SGA score, while negatively with serum albumin﹑TSF. The fasting plasma levels of toal ghrelin﹑serum albumin was negative correlation with age respectively, while CRP﹑the ghrelin-leptin ratio positive correlation with age. The negative relationship between serum albumin and CRP was found in dialysis groups.
Conclusions
The fasting plasma ghrelin levels and the ratio betwee plasmsa ghrelin and leptin levels are higher in hemodialysis(HD) patients. The abnormal secretion of ghrelin and leptin are associate with anorexia﹑malnutrition micro-inflammation in HD patients. Ghrelin secretion may increase under the regulatory effect of negative feedback in the event of anorexia, malnutrition, micro-inflammatory, while leptin reduce. Further to define the mechanism of abnormal secretion of ghrelin﹑leptin in HD patients will give a new direction of solving malnutrition- Inflammation- Atherosclerosis(MIA) Syndrome problem. Ghrelin inadequate secretion in senile patients with inadequate compensation may be one of the factors cause them prone to anorexia, malnutrition, micro-inflammatory. Ghrelin may be a new promising way as a new drug.to treat HD patients with anorexia, malnutrition, cardiovascular disease.
研究维持性血液透析患者生长激素释放肽(ghrelin)、瘦素(leptin)的血浆水平。探讨影响它们血浆水平的因素,揭示它们的分泌失调是否与这些患者的食欲缺乏、营养不良、微炎症、胰岛素抵抗代谢综合征有关。进一步了解它们在这些患者中的调节作用。为治疗这些患者相关并发症开拓新的领域。
方法
采用酶联免疫吸附测试法测量30个维持性血液透析患者和15个对照的健康者总的ghrelin、leptin血浆水平。并测量透析组患者营养状况、微炎症、胰岛素抵抗代谢综合征相关的体格检查和血生化指标。通过改良主观营养评估和食欲调查问卷对透析组患者进行营养状况和食欲评估。比较透析组和对照组,透析组中食欲正常A组与食欲缺乏B组、体重指数小于20组和大于20组、营养正常组和营养不良组之间总的ghrelin、leptin血浆水平及它们比值的均数差别。并探讨总的ghrelin、leptin的血浆水平及它们的比值分别与年龄及营养状况、微炎症、代谢综合征相关标志物的关联。
结果
与对照组相比,透析组空腹总的ghrelin血浆水平、总的ghrelin与leptin血浆水平的比值均数显著高于对照组,而leptin的血浆水平均数没有显著的差别。在透析组中,食欲正常A组的leptin的血浆水平均数显著高于食欲缺乏B组,而总的ghrelin的血浆水平均数显著低于食欲缺乏组,体重指数小于20和大于20组、营养正常和营养不良组之间总的ghrelin、leptin血浆水平及它们比值的均数差别无显著统计意义。在透析组中,空腹leptin血浆水平与肱三头肌皮褶厚度成显著正相关,而与体重、上臂肌围、小腿围成显著负相关。总的ghrelin与leptin血浆水平的比值与血清C反应蛋白(CRP)、改良主观营养评估(SGA)评分成显著正相关,而与血清白蛋白、肱三头肌皮褶厚度成负相关。总的ghrelin血浆水平、血清白蛋白分别与年龄成负相关,而CRP和总的ghrelin与leptin血浆水平的比值分别与年龄成正相关。血清白蛋白又与CRP成负相关。
结论
维持性血液透析患者总的ghrelin血浆水平和总的ghrelin与leptin血浆水平的比值都显著高于对照组。透析组患者发生食欲缺乏、营养不良、微炎症与ghrelin、leptin的分泌失调有关。Ghrelin在发生食欲缺乏、营养不良、微炎症的状况下可能存在负反馈的分泌增加作用,而同时leptin存在负反馈的减少作用。进一步明确ghrelin、leptin在维持性血液透析患者中分泌失调的机制对解决营养不良-微炎症-动脉粥样硬化综合症的难题的研究指出新的方向。ghrelin在老年性患者分泌代偿不足可能是导致他们容易发生食欲缺乏、营养不良、微炎症的因素之一。ghrelin作为一种新药治疗这些患者发生食欲缺乏、营养不良、心血管疾病带来新的展望。
Objective
The aim of study is to investigate the fasting plasma total ghrelin and leptin levels in hemodialysis patients. The factors that affect their plasma levels are also explored. We like to reveal whether their levels are abnormal in these patients with anorexia, malnutrition, micro-inflammation, insulin resistance related metabolic syndrome. We want further to understand their regulatory role in these patients and open up new areas for the treatment of these patients related complications.
Methods
The levels of fasting total ghrelin and leptin were measured by ELISA in 30 hemodialysis patients and 15 normal controls. We also measured the medical examination and blood biochemical markers about nutritional status﹑micro-inflammation﹑metabolic syndrome in dialysis patients. The nutritional and appetite status of dialysis patients were assessed by the modified quantitative subjective gloval assessment(SGA) nutrition and subjective appetite questionnaire. We compared the plasma total ghrelin﹑leptin levels and their ratio between dialysis and control group, normal appetite dialysis groups A and groups B with anorexia, body mass index (BIM)<20 dialysis groups and BIM>20 groups, nutrition normal dialysis groups and the malnourished groups. We also explored the correlations between the plasma total ghrelin﹑leptin levels,their ratio and age, selected nutritional﹑inflammation﹑metabolic syndrome markers respectively.
Results
The fasting plasma toal ghrelin levels and the ratio betwee plasmsa ghrelin and leptin levels in dialysis groups were higher than that in controls.However,there was no difference in the fasting plasma leptin levels between them. In the dialysis groups, the fasting plasma leptin levels were significantly higher in the normal appetite group A than that in the anorexia group B, while the total plasma ghrelin levels lower than the anorexia group B.There were no significant differences in the fasting plasma toal ghrelin﹑leptin levels and their ratio between the BIM<20 and>20 groups, the normal nutrition and unnutrition groups(by SGA) respectively in dialysis groups. The fasting plasma leptin levels was positively correlated with body weigh﹑triceps skinfold(TSF),and negatively with midarm muscle circumference(MAC)﹑calf circumference in dialysis patients. The ghrelin-leptin ratio was positively correlated with serum C-reactive protein(CRP)﹑the modified quantitative SGA score, while negatively with serum albumin﹑TSF. The fasting plasma levels of toal ghrelin﹑serum albumin was negative correlation with age respectively, while CRP﹑the ghrelin-leptin ratio positive correlation with age. The negative relationship between serum albumin and CRP was found in dialysis groups.
Conclusions
The fasting plasma ghrelin levels and the ratio betwee plasmsa ghrelin and leptin levels are higher in hemodialysis(HD) patients. The abnormal secretion of ghrelin and leptin are associate with anorexia﹑malnutrition micro-inflammation in HD patients. Ghrelin secretion may increase under the regulatory effect of negative feedback in the event of anorexia, malnutrition, micro-inflammatory, while leptin reduce. Further to define the mechanism of abnormal secretion of ghrelin﹑leptin in HD patients will give a new direction of solving malnutrition- Inflammation- Atherosclerosis(MIA) Syndrome problem. Ghrelin inadequate secretion in senile patients with inadequate compensation may be one of the factors cause them prone to anorexia, malnutrition, micro-inflammatory. Ghrelin may be a new promising way as a new drug.to treat HD patients with anorexia, malnutrition, cardiovascular disease.
引文
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65)Tamura MK. Incidence management, and outcomes of end-stage renal disease in the elderly. Curr Opin Nephrol Hypertens .2009V18N3:252-257
66)曹礼应余月明等,老年血液透析者颈动脉粥样硬化与C反应蛋白的关系,实用老年医学,2006年第20卷第3期
1] Teruel JL,de la Cal MA.The impact of malnutrition in morbidity and mortality in stable haemodialysis patients. Spanish Cooperative Study of Nutrition in Hemodialysis[J]. Nephrol Dial Transplant 1997,12:2324-2331.
2]刘惠兰.维持性血液透析患者营养问题[J].中国血液化,2006,5:703-706.
3] Mitch WE, Maroni BJ. Factors causing malnutrition ipatients with chronicuremia[J]. Am J Kidney Dis1999,33:176-179.
4]Koo JR, Yoon JW, Kim SG,Association of depression with malnutrition in chronic hemodialysis patients[J].Am Kidney Dis, 2003,41:1037-1042.
5] Burrowes JD;Larive B;Chertow GM;Self-reported appetite, hospitalization and death in haemodialysis patients: findings from the Hemodialysis(HEMO) Study[J]NephrolDialTransplant,2005,20:2765-2774.
6] Herselman M;Moosa MR;Kotze TJ.Protein-energy malnutrition as a risk factor for increased morbiditin long-term hemodialysis patients[J]. J Ren Nutr2000,10:7-15.
7] Bossola M,Tazza L,Luciani G. Mechanisms and treatmen of anorexia in end-stage renal disease patients on hemodialysis[J].J Ren Nutr, 2009, 19:2-9.
8]Kojima M,Hosoda H,Date Y,et al.Ghrelin is a growth hormon-releasing cylated peptide from stomac[J].Nature,1999,402:656-660.
9] Kojima M, Kangawa K.Ghrelin:structure and function[J]Physiol Rev, 2005, 85:495-522.
10] Hosoda H,Kojima M,Matsuo H,et al.Ghrelin and des-acyl ghrelin: two major forms of rat ghrelin peptide in gastrointestinal tissue[J].Biochem Biophys Res Commun2000, 279:909-913.
11] Tschop M, Smiley DL,Heiman ML.Ghrelin induces adiposit in rodents[J]nature, 2000, 407:908-913.
12] Cassoni P,Papotti M,Ghe C,et al. Identification,charac eriztion,and biological activity of specific receptor for natural(ghrelin)and synthetic growth hormone secre agogues and analogs in human breast carcinomas and cell ines[J]. J Clin Erdocrinol Metab, 2001, 86:1738-1745.
13] Cumming DE ,Parnell JQ, Fray RS,et al.A prepandial rise in plasma levels suggests a role in meal initation I humans[J]. Diabets, 2001, 50: 1714-1719.
14] Overduin J, Frayo RS,Grill HJ,et al. Role of the duodenum and macronutrient type in ghrelin regulation[J]Edocrinonlogy, 2005,146:845-850.
15] Weigle DS, Cummings DE ,Newby PD, et al. role of lepte and ghrelin in the loss of body weight caused by a lofat,high carbohydrate diet[J].J clin Endocrinol Metab2003, 88:1577-1586.
16]Anderwald C,Brabant G,Bernroider E, et al.Insulin dependent modulation of plasma ghrelin and leptin concentrations is less pronounced in type 2 diabeti patients[J].Diabets, 2003, 52:1972-1978.
17] Williams DL,Grill HJ,Cummings DE,et al.Vagotomy dissociates short-and long-term controls of circulatin ghrelin[J].endocrinology, 2003,144:5184-5187.
18] Norrelund H Hansen TK,Orskov H, et al.Gherlin immunoreactivity in human plasma is suppressed by somatostain [J].Clin Endocrinol,2002,57:539-546.
19] Tentolouris N, Makrilakis K, Doulgerakis D,et al. Increased plasma ghrelinlevels in chronic renal failure are not associated with hemodynamic parameters[J]. Horm Metab Res, 2005,37:646-652.
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62)陈秀益,刘必成,尹莲芳,微炎症反应状况与终末期肾病,临床荟萃,2005年6月20卷第12期
63)Caglar K,Hakim RM,lkizler TA.Approaches to the reversal of malnutrltion,inflammation,and atherosclerosis in end stage renal disease J.Nutr Rev,2002,60(儿):378.
64) Feldt Rasmussen B Growth hormone treatment during hemodialysis in a randomized trial improves nutrition, quality of life, and cardiovascular risk.J Am Soc Nephrol.2007V18N7:2161-2171
65)Tamura MK. Incidence management, and outcomes of end-stage renal disease in the elderly. Curr Opin Nephrol Hypertens .2009V18N3:252-257
66)曹礼应余月明等,老年血液透析者颈动脉粥样硬化与C反应蛋白的关系,实用老年医学,2006年第20卷第3期
1] Teruel JL,de la Cal MA.The impact of malnutrition in morbidity and mortality in stable haemodialysis patients. Spanish Cooperative Study of Nutrition in Hemodialysis[J]. Nephrol Dial Transplant 1997,12:2324-2331.
2]刘惠兰.维持性血液透析患者营养问题[J].中国血液化,2006,5:703-706.
3] Mitch WE, Maroni BJ. Factors causing malnutrition ipatients with chronicuremia[J]. Am J Kidney Dis1999,33:176-179.
4]Koo JR, Yoon JW, Kim SG,Association of depression with malnutrition in chronic hemodialysis patients[J].Am Kidney Dis, 2003,41:1037-1042.
5] Burrowes JD;Larive B;Chertow GM;Self-reported appetite, hospitalization and death in haemodialysis patients: findings from the Hemodialysis(HEMO) Study[J]NephrolDialTransplant,2005,20:2765-2774.
6] Herselman M;Moosa MR;Kotze TJ.Protein-energy malnutrition as a risk factor for increased morbiditin long-term hemodialysis patients[J]. J Ren Nutr2000,10:7-15.
7] Bossola M,Tazza L,Luciani G. Mechanisms and treatmen of anorexia in end-stage renal disease patients on hemodialysis[J].J Ren Nutr, 2009, 19:2-9.
8]Kojima M,Hosoda H,Date Y,et al.Ghrelin is a growth hormon-releasing cylated peptide from stomac[J].Nature,1999,402:656-660.
9] Kojima M, Kangawa K.Ghrelin:structure and function[J]Physiol Rev, 2005, 85:495-522.
10] Hosoda H,Kojima M,Matsuo H,et al.Ghrelin and des-acyl ghrelin: two major forms of rat ghrelin peptide in gastrointestinal tissue[J].Biochem Biophys Res Commun2000, 279:909-913.
11] Tschop M, Smiley DL,Heiman ML.Ghrelin induces adiposit in rodents[J]nature, 2000, 407:908-913.
12] Cassoni P,Papotti M,Ghe C,et al. Identification,charac eriztion,and biological activity of specific receptor for natural(ghrelin)and synthetic growth hormone secre agogues and analogs in human breast carcinomas and cell ines[J]. J Clin Erdocrinol Metab, 2001, 86:1738-1745.
13] Cumming DE ,Parnell JQ, Fray RS,et al.A prepandial rise in plasma levels suggests a role in meal initation I humans[J]. Diabets, 2001, 50: 1714-1719.
14] Overduin J, Frayo RS,Grill HJ,et al. Role of the duodenum and macronutrient type in ghrelin regulation[J]Edocrinonlogy, 2005,146:845-850.
15] Weigle DS, Cummings DE ,Newby PD, et al. role of lepte and ghrelin in the loss of body weight caused by a lofat,high carbohydrate diet[J].J clin Endocrinol Metab2003, 88:1577-1586.
16]Anderwald C,Brabant G,Bernroider E, et al.Insulin dependent modulation of plasma ghrelin and leptin concentrations is less pronounced in type 2 diabeti patients[J].Diabets, 2003, 52:1972-1978.
17] Williams DL,Grill HJ,Cummings DE,et al.Vagotomy dissociates short-and long-term controls of circulatin ghrelin[J].endocrinology, 2003,144:5184-5187.
18] Norrelund H Hansen TK,Orskov H, et al.Gherlin immunoreactivity in human plasma is suppressed by somatostain [J].Clin Endocrinol,2002,57:539-546.
19] Tentolouris N, Makrilakis K, Doulgerakis D,et al. Increased plasma ghrelinlevels in chronic renal failure are not associated with hemodynamic parameters[J]. Horm Metab Res, 2005,37:646-652.
[20] Perez-FontanM,CordidoF,Rodriguez-CarmonaA,et al. Plasma ghrelin levels in paitents undergoing hemodi-alysis and peritoneal dialysis[J]. Nephrol Dial Trans-plant,2004,19:2095-2100.
[21] Schmidt A, Fabrizii V, Maier C, et al.Normal regulation of elevated plasma ghrelin concentrations in dialysis patients[J]. Wien Klin Wochenschr, 2004,116:235-239.
[22]张昭馥,臧贵明,血液透析患者血浆ghrelin测定的初步分析[J],中华肾脏病杂志,2002,18:20.
[23] Barazzoni R, Zanetti M, Stulle M, et al. Higher to-tal ghrelin levels are associated with higher insulin-mediated glucose disposal in non-diabetic maintenance hemodialysis patients[J]. Clin Nutr, 2008, 27:142-149.
[24] Yoshimoto A, Mori K, Sugawara A, et al.Plasma ghrelin and desacyl ghrelin concentrations in renal failure[J]. J Am Soc Nephrol,2002, 13:2748-2752.
[25] JarkovskáZ, RosickáM, Krsek M, et al. Plasma ghrelin levels in patients withend-stage renal disease[J]. Physiol Res,2005,54:403-408.
[26] Jarkovska Z,Hodkova M,Sazamova M.Plasma levels of ac-tive and totalghrelin in renal failure: a relation-ship with GH/IGF-I axis[J]. Growth Horm IGF Res, 2005,15:369-376.
[27] Barazzoni R, Zanetti M, Biolo G.Metabolic effects of ghrelin and its potential impli-cations in uremia[J]. J Ren Nutr,2005, 15:111-115.
[28]Anderwald C, Brabant G,Bernroider E,et al.Insulin-dependent modulation of plasma ghrelin and letptin concentrations is less pronouced in type 2 diabectic patients[J].Diabetes, 2003,52:1792-1798.
[29] Bossola M, Scribano D, Colacicco L, et al.Anorexia and Plasma Levels of Free Tryptophan, Branched Chain Amino Acids, and Ghrelin in Hemodialysis Patients[J]. JRen Nutr, 2009,2: 23. [Epub ahead of print]
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