Ghrelin与消化系统疾病的研究进展

Ghrelin是一个由28个氨基酸组成的脑肠肽,是在1999年由Kojima等[1]发现的生长素促分泌激素受体的内源性配体,与其受体结合后可产生广泛的生物学效应,具有促生长激素分泌作用的同时,具有增强食欲,减少脂肪利用,增加体重,维持能量正平衡的调节能量代谢的作用。另外,Ghrelin还控制胃动力,促进胃酸分泌,调节胰腺的内外分泌功能,影响血糖水平。Ghrelin与胃肠道类腺癌有关。最近研究发现,它的拮抗剂能减慢结肠传输时间。现将Ghrelin与消化系统相关疾病的研究进展综述如下。1概述1.1Ghrelin的分子结构Ghrelin是由28个氨基酸组成的小分子多肽,人…     

Ghrelin的胃肠动力学研究进展

Ghrelin是1999年被发现的生长激素促分泌激素受体的内源性配体,是胃动素相关类家族的调节肽。Ghrelin主要由胃基底部泌酸腺X/A样细胞分泌,并释放进入血液循环。它除了可以刺激生长激素、泌乳刺激素及促肾上腺皮质激素释放外,还可以促进食欲、增强胃肠动力、刺激胃酸分泌、影响睡眠节律、调节胰腺内分泌功能、调节糖代谢、能量代谢等。此文综述了Ghrelin在胃肠动力方面的研究进展。     

Ghrelin在消化系统的作用

Ghrelin是一种生长激素释放激素受体的内源性配体,具有调节生长激素和其他激素的分泌、促进摄食、调节能量代谢和胃肠功能等多种生物学作用。Ghrelin及其受体在下丘脑、垂体、胃、胰腺、肾脏、唾液腺等脏器中都有表达,可能是脑与胃肠道之间调节内分泌的一种介质,有望在诊断和治疗某些消化系统疾病中发挥一定的作用。此文就ghrelin对消化系统功能的调节作用作一简要综述。     

Ghrelin与生长激素关系的研究进展

Ghrelin是最近发现的一种脑—肠肽,具有强烈的促生长激素(GH)释放的作用,此外还能调节能量代谢、食欲、睡眠等。目前认为,ghrelin可同时作用于人体腺垂体和下丘脑,与促生长激素释放激素协同促进GH分泌。Ghrelin的分泌具有性别差异,可被生长抑素抑制,但外周GH水平对ghrelin的分泌无明显影响。另外,胰岛素样生长因子1可通过下调ghrelin受体的表达而影响其作用。     

Ghrelin与生长激素关系的研究进展

Ghrelin是最近发现的一种脑-肠肽,具有强烈的促生长激素（GH）释放的作用,此外还能调节能量代谢、食欲、睡眠等.目前认为,ghrelin可同时作用于人体腺垂体和下丘脑,与促生长激素释放激素协同促进GH分泌.Ghrelin的分泌具有性别差异,可被生长抑素抑制,但外周GH水平对ghrelin的分泌无明显影响.另外,胰岛素样生长因子1可通过下调ghrelin受体的表达而影响其作用.     

Ghrelin与消化系统疾病

Ghrelin是由Kojima等于1999年发现的一种28肽，该物质最初由大鼠胃组织提取物中分离得到，是生长激素促分泌物受体 （growth hormone secretagogue receptor, GHSR）的天然内源性配体，能促进生长激素（GH）释放。进一步的研究表明．ghrelin主要来源于胃肠道，也可由下丘脑、垂体和多种外周组织器官产生。其受体在体内广泛分布，具有调节GH分泌、摄食和能量平衡，影响神经内分泌以及胃肠功能、心血管系统、记忆、睡眠等多种生物学作用，是近年来研究的热点。     

Ghrelin研究进展

Ghrelin具有促进食欲,增加体重的作用,并可升高血糖、减少胰岛素分泌。肥胖人群中Ghrelin水平下降,高胰岛素可抑制Ghrelin分泌     

血浆胃动素水平与十二指肠球部溃疡发生与愈合的关系

本文用放免法测定了３３例十二指肠球部溃疡及３５例慢性胃炎患者血浆胃动素水平，同时检测胃粘膜ＨＰ感染情况及胃液ｐＨ值，并对其中１９例十二指肠球部溃疡患者进行抗ＨＰ二联治疗（得乐冲剂＋甲硝唑片）共６周，观察ＨＰ转阴后胃动素变化，结果表明十二指肠球部溃疡患者血浆胃动素显著高于慢性胃炎患者，分别为４４７．２３±９８．４ｎｇ／Ｌ及３５３．５±１００．２ｎｇ／Ｌ（Ｐ＜０．０１），１７例溃疡愈合者血浆胃动素显著下降，与慢性胃炎愈合者无显著性差异（Ｐ＞０．０５），而２例溃疡未愈者血浆胃动素仍持续升高，相关分析显示十二指肠球部溃疡患者血浆胃动素升高与ＨＰ感染及胃液ｐＨ值无关。本文认为十二指肠球部溃疡患者血浆胃动素升高可能是一种继发性改变，其临床意义尚有待进一步阐明。     

Ghrelin与胃肠疾病关系的研究进展

Ghrelin是生长激素促分泌素受体的内源性配体,与受体结合后产生广泛的生物学效应,可刺激生长激素分泌、调节能量代谢等作用.而在消化系统中,Ghrelin具有保护胃肠黏膜、调节胃肠动力、促进胃酸分泌及控制肿瘤细胞增殖的作用,现将其与胃肠病疾病的研究进展综述如下.     

Ghrelin研究进展

Ghrelin是 1999年被发现的第一个生长激素促分泌素受体的内源性配体,由 28个氨基酸组成,第三位丝氨酸残基上有辛酰化基团。Ghrelin主要由胃的X/A样细胞合成,在中枢神经系统、肠、肾、心脏、胎盘、性腺也有分泌。其受体广泛分布于多种组织,并存在不同的亚型。Ghrelin与受体结合后,可产生一系列生物学效应,如促进生长激素的释放;增强食欲,维持能量正平衡;促进胃酸的分泌,增加胃肠蠕动等,并与糖尿病、肥胖、肿瘤、肝硬化等多种疾病有关。     

The Relations Among Serum Ghrelin,Motilin and Gastric Emptying and Autonomic Function in Autoimmune Gastritis

Background

Gastric emptying (GE) of solids is delayed and autonomic dysfunction is detected in autoimmune gastritis (AIG). The goals of this study were to: (1) compare serum levels of ghrelin and motilin in subjects with delayed and normal GE and (2) investigate whether circulating antimyenteric antibodies (CAA), serum ghrelin levels and motilin levels have any effect on autonomic function.

十二指肠球部溃疡患者Ghrelin水平及相关因素分析

目的 观察不同期十二指肠球部溃疡患者Ghrelin、一氧化氮（NO）、环氧合酶-2（COX-2）的水平变化,探讨幽门螺杆菌（Hp）感染对患者Ghrelin、COX-2表达水平的影响.方法 选取我院2010年11月～2011年6月就诊的慢性胃炎及十二指肠球部溃疡患者80例,酶联免疫吸附试验（ELISA法）检测其血浆Ghrelin浓度,硝酸还原酶法检测NO浓度,免疫组化法检测胃黏膜组织COX-2及Ghrelin表达.结果 十二指肠球部溃疡活动期患者血清Ghrelin水平为（3.52±0.61）ng/ml,高于愈合期[（3.02±0.58） ng/ml]、疤痕期[（2.94±0.36） ng/ml]及慢性胃炎组[（2.87±0.48） ng/ml];胃黏膜组织免疫组化检测结果显示活动期Ghrelin及COX-2呈强阳性表达,其阳性点数百分比分别为70.50±5.56和62.41±7.13,高于愈合期（56.54±7.08,46.38±7.42）、疤痕期（51.50±5.76,40.36±8.35）和慢性胃炎期（53.38±6.74,42.38±4.96）,两者之间相关系数为0.68（P ＜0.05）;Hp阳性及阴性患者Ghrelin表达比较差异无统计学意义（P＞0.05）;4组患者血浆NO水平比较差异无统计学意义（P＞0.05）,且与血浆Ghrelin水平无明显相关性（r=0.113,P＞0.05）.结论 十二指肠球部溃疡活动期患者Ghrelin、COX-2表达增加,Ghrelin、COX-2可能与溃疡活动存在一定关系,Ghrelin与COX-2呈正相关.Ghrelin的表达与有无Hp感染无关.十二指肠球部溃疡患者血浆NO水平无明显变化,且与血浆Ghrelin的水平无明显相关.     

Ghrelin improves delayed gastrointestinal transit in alloxan-induced diabetic mice

AIM： To investigate the effects of ghrelin on delayed gastrointestinal transit in alloxan-induced diabetic mice. METHODS： A diabetic mouse model was established by intraperitoneal injection with alloxan. Mice were randomized into two main groups： normal mice group and diabetic mice group treated with ghrelin at doses of 0, 20, 50, 100 and 200 μg/kg ip. Gastric emptying （GE）, intestinal transit （IT）, and colonic transit （CT） were studied in mice after they had a phenol red meal following injection of ghrelin. Based on the most effective ghrelin dosage, atropine was given at 1 mg/kg 15 min before the ghrelin injection for each measurement. The mice in each group were sacrificed 20 min later and their stomachs, intestines, and colons were harvested immediately. The amount of phenol red was measured. Percentages of GE, IT, and CT were calculated. RESULTS： Percentages of GE, IT, and CT were significantly decreased in diabetic mice as compared to control mice （22.9 ± 1.4 vs 28.1 ± 1.3, 33.5 ± 1.2 vs 43.2 ± 1.9, 29.5 ± 1.9 vs 36.3 ± 1.6, P 〈 0.05）. In the diabetic mice, ghrelin improved both GE and IT, but not CT. The most effective dose of ghrelin was 100 μg/kg and atropine blocked the prokinetic effects of ghrelin on GE and IT.CONCLUSION： Ghrelin accelerates delayed GE and IT but has no effect on CT in diabetic mice. Ghrelin may exert its prokinetic effects via the cholinergic pathway in the enteric nervous system, and therefore has therapeutic potential for diabetic patients with delayed upper gastrointestinal transit.     

老年非溃疡性消化不良患者胃液体排空与血浆胃动素、生长抑素关系的研究

采用实时超声显像法与放射免疫法,对20例老年NUD患者及15例对照者进行胃液体排空时间的测定及血浆胃动素、生长抑素的检测,探讨老年NUD患者目排空运动与胃肠激素之间的关系.结果显示:老年NUD患者胃液体排空T1/2为39.00±11.65min,较对照组的29.33±7.99min明显延迟(P<0.01).老年NUD患者胃动素浓度为471.5±63.06pg/ml,生长抑素浓度为63.83±11.88pg/ml,较对照组分别下降和升高(P均<0.01).老年NUD患者胃液体排空T1/2与胃动素浓度呈负相关(r=-0.936,P<0.01),与生长抑素浓度呈正相关(r=0.942,P<0.01).表明老年NUD患者胃液体排空障碍与胃动素分泌下降及生长抑素分泌增高相关.     

肝硬化患者血浆胆囊收缩素及胃动素对胃排空的影响

目的本研究旨在探讨肝硬化患者胃排空功能,并探讨其胃排空作用与空腹血浆胆囊收缩素、胃动素的关系,进而为预防和治疗肝硬化提供参考。方法 将30例肝硬化患者作为试验组,30例健康志愿者作为对照组,采用^13C-辛酸呼气试验法测定肝硬化患者以及对照组的胃固体半排空时间（GET1／2）,同时用放射免疫技术测定患者及对照组的空腹血浆胆囊收缩素（CCK）及胃动素（MTL）水平。结果与健康志愿者组相比,肝硬化患者组GET1／2明显延迟（P〈0．05）;空腹血浆CCIK及MTL水平明显升高,组间差异有统计学意义（P〈0．05）;患者GET1／2与空腹血浆CCK及MTL水平各自呈正相关。结论肝硬化患者胃排空延迟可能与血浆CCK及MTL水平的异常增高相关。推测肝硬化时血浆CCK及MTL水平均明显增高,由此引发胃排空延迟,最终导致营养不良,进而加重患者病情。     

Gender Differences in Plasma Ghrelin Levels in Hemodialysis Patients

Ghrelin is an orexigenic hormone mainly secreted by the stomach, and it decreases according to the severity of gastric atrophy. Ghrelin has multiple favorable functions, including protein anabolism enhancement, anti‐inflammatory activity, and cardiovascular protection, and is associated with survival in hemodialysis (HD) patients. Although the plasma level and role of ghrelin may be different depending on gender, they have not been completely assessed in HD patients. We enrolled 80 (male/female: 51/29) maintenance HD patients. An upper gastrointestinal endoscopic examination was performed for all patients to determine the severity of gastric mucosal atrophy and Helicobacter pylori infection. We measured plasma acyl and desacyl ghrelin levels and assessed the association between ghrelin levels and relevant clinical parameters, including nutrition, inflammation, atherosclerosis, and bone metabolism, by gender. Both acyl and desacyl ghrelin levels in female HD patients were significantly higher than those in male HD patients. When stratified by gastric mucosal atrophy, these gender differences were observed only in patients without gastric atrophy. In female patients, acyl ghrelin level was negatively correlated with age. In male patients, both acyl and desacyl ghrelin levels were positively correlated with bone mineral density. Multiple regression analysis showed significant positive correlations between both ghrelin levels and female gender after adjusting for confounding factors. Plasma ghrelin levels were higher in female HD patients than in male HD patients. The gender difference was more evident in patients without gastric atrophy.     

Accelerated gastric emptying during hypoglycaemia is not associated with changes in plasma motilin levels

This study examined whether or not changes in plasma concentrations of motilin and other gastrointestinal hormones known to affect gastric motility are associated with the accelerated gastric emptying seen during hypoglyc-aemia. While studying gastric emptying by scintigraphy in eight healthy subjects, the plasma concentrations of glucagon, adrenaline, motilin, gastrin, neuropeptide Y and somatostatin were measured during normoglycaemia and hypoglycaemia with simultaneous infusion of either atropine or saline. Blood glucose concentrations were checked by an insulin-glucose clamp. The plasma levels of glucagon and adrenaline increased markedly during both hypoglycaemic examinations compared with normoglycaemia. Neither motilin nor any of the other hormones displayed considerable changes during hypoglycaemia with and without atropine compared with normoglycaemia. No further information about the mechanisms behind the accelerated gastric emptying rate during hypoglycaemia was obtained by analysing motilin and the other gastrointestinal hormones. Received: 1 January 1997 / Accepted in revised form: 8 May 1997     

Influence of H pylori on plasma ghrelin in patients without atrophic gastritis

AIM:To determine the association between H pylori infection and serum ghrelin levels in patients without atrophic gastritis.METHODS:Fifty consecutive patients(24 males and 26 females)with either H pylori-positive gastritis(n = 34)or H pylori-negative gastritis(n = 16)with normal gastric acid secretion determined by 24-h pHmetry and without atrophic gastritis in histopathology were enrolled in this study.Thirty-four H pylori-infected patients were treated with triple therapy consisting of a daily regimen of 30 mg lansoprazole bid,1 g amoxicillin bid and 500 mg clarithromycin bid for 14 d,followed by an additional 4 wk of 30 mg lansoprazol treatment.H pylori infection was eradicated in 23 of 34(67.6%)patients.H pylori-positive patients were given eradication therapy.Gastric acidity was determined via intragastric pH catethers.Serum ghrelin was measured by radioimmunoassay(RIA).RESULTS:There was no signifficant difference in plasma ghrelin levels between H pylori-positive and H pylori-negative groups(81.10 ± 162.66 ng/L vs 76.51 ± 122.94 ng/L).In addition,there was no significant difference in plasma ghrelin levels and gastric acidity levels measured before and 3 mo after the eradication therapy.CONCLUSION:H pylori infection does not influence ghrelin secretion in patients with chronic gastritis without atrophic gastritis.     

Ghrelin and Helicobacter pylori infection

Ghrelin is primarily secreted from the stomach and has been implicated in the coordination of eating behavior and weight regulation. Ghrelin also plays an essential role in the mechanism of gastric mucosal defense. Thus, it is important to clarify which diseases primar- ily influence changes in plasma ghrelin concentrations. Helicobacter pylori （H pylor/~ infection is involved in the pathogenesis of gastritis, gastric and duodenal ulcer, gastric carcinoma, and mucosa-associated lym- phoid tissue lymphoma. H pylori eradication is related to body weight change. Compared, H pylori infected and negative subjects with normal body mass index, plasma ghrelin concentration, gastric ghrelin mRNA, and the number of ghrelin producing cells in gastric mucosa are significantly lower in Hpylori infected sub- jects than in Hpylori-negative controls. Plasma ghrelin concentration decreases with the progression of gastric atrophy. Impaired gastric ghrelin production in associa- tion with atrophic gastritis induced by Hpylori infection accounts for the decrease in plasma ghrelin concentra- tion. However, the ratio of plasma acylated ghrelin to total ghrelin levels is higher in patients with chronic atrophic gastritis than in healthy subjects. This may re- sult from the＇ compensatory increase in plasma active ghrelin concentration in response to gastric atrophy. After H pylori eradication, gastric preproghrelin mRNA expression is increased nearly 4-fold in most cases. However, changes in plasma ghrelin concentrations be- fore and after Hpylori cure are not associated with the gastric ghrelin production. Plasma ghrelin changes are inversely correlated with both body weight change and initial plasma ghrelin levels.     

急性心肌梗死大鼠胃排空的变化

目的观察急性心肌梗死(AMI)大鼠胃排空的变化,并探讨其可能的作用机制。方法对12只 AMI 模型大鼠(AMI 组)和9只假手术大鼠(假手术组)用锝~(99m)亚锡喷替酸~(99m)TcDTPA)标记的面粉糊灌胃后,分别在单光子发射计算机断层照相仪下进行胃排空功能检查;50min后处死 AMI 组大鼠,氯化-2,3,5-三苯基四氮唑染色法计算心肌梗死面积:同时取 AMI 组、假手术组大鼠各9只,放射免疫法测定血浆胃动素。结果 AMI 组胃半排空时间(GET_(1/2))为(23.1±4.7)min,50min 胃内核素残留率为(27.6±4.5)%,假手术组分别为(16.0±4.0)min 和(18.1±3.3)%,两组差异有统计学意义(均为 P<0.01)。AMI 组心肌梗死面积为(52.1±4.1)%,与50min 胃内核素残留率呈正相关(r=0.620,P=0.031)。AMI 组、假手术组血浆胃动素分别为(81.5±17.6)ng/L、(103.8±24.9)ng/L,AMI 组较假手术组降低(P<0.01)。结论 AMI 大鼠胃排空明显减慢,胃内核素残留率与梗死而积呈正相关性;胃排空减慢与胃动素分泌减少有关。