老年功能性消化不良患者胆囊收缩素浓度及其与胃运动的关系

目的探讨老年功能性消化不良(FD)患者血浆胆囊收缩素浓度及其与胃排空运动的关系。方法用超声显像法检测15例老年FD患者和15例老年健康志愿者静脉输入生理盐水及生理浓度的胆囊收缩素(CCK)后的胃排空情况,用放免法测定空腹和餐后血浆CCK浓度。结果15例老年FD患者的胃排空时间与正常对照组比较明显延长(P<0.01),胃动力指数明显降低(P<0.01),血浆CCK浓度显著高于正常对照组(P<0.01)。结论血浆CCK浓度升高是老年FD患者胃运动功能障碍的重要原因之一。     

腹腔镜胆囊切除术前、后胆囊收缩素的变化分析

胆囊收缩素（CCK）是一种脑肠肽，它广泛分布于中枢及外周神经系统，能引起胆囊收缩的肠道多肽激素，胆囊切除后，该激素将会如何变化，作为此对腹腔镜胆囊切除术前、后的患血浆中CCK-8进行测定，以观察其术前、后CCK-8的变化。     

糖胃安对糖尿病胃轻瘫患者胃电节律及MLT、CCK影响的临床研究

目的探讨糖胃安对糖尿病胃轻瘫患者胃电节律及血浆胃动素（MLT）、胆囊收缩素（CCK）的影响。方法选择糖尿病胃轻瘫患者354例，分为糖胃安治疗组（213例）和吗丁林对照组（141例）治疗8周，观察并比较治疗前后胃电图、血浆MLT、CCK的改变情况。结果治疗后两组患者胃电节律明显好转，血浆MLT及CCK表达明显下降，与治疗前相比有明显差异（P〈0．05），而且糖胃安治疗组疗效明显优于吗丁林对照组（P〈0．05）。结论糖胃安可明显改善胃电节律并能改善糖尿病胃轻瘫患者的胃肠激素的异常。     

糖尿病并发胆囊结石病人CCK受体表达意义的探讨

缩胆囊素（CCK）是一类广泛分布于消化系统和中枢神经系统的内源性多肽,在消化系统中可调控胃酸和胰酶分泌、胃排空等生理过程。依据介导的生理功能不同,CCK受体被分为CCK-1（主要分布在消化系统）和CCK-2（主要分布在CNS）两种亚型。CCk受体的作用是受FGF19拮抗的,FGF19是在餐后1-2h引起胆囊舒张,FGF19和CCK的交替作用引起胆囊的舒张和收缩。     

惊恐障碍相关CCK系统基因多态性研究进展

遗传学研究发现惊恐障碍具有家族聚集性,神经生化研究证实中脑皮层的DA能系统与胆囊收缩素受体（CCK-B）共存于CNS内,经安定药长期治疗后,中脑DA神经元CCK mRNA的表达量明显升高。本文综述了惊恐障碍相关CCK亚型,CCK及其受体基因多态性近年来进展。     

抑制素B与多囊卵巢综合征的相关性研究

目的：检测抑制素B在多囊卵巢综合征（PCOS）患者卵巢组织中的表达,探讨其在PCOS患者发病中的可能机制。方法：PCOS患者30例,对照组30例。分别测定血清促卵泡激素（FSH）、促黄体生成素（LH）、垂体催乳素（PRL）、睾酮（T）、雌二醇（E2）性激素水平。通过免疫组化方法检测抑制素B在卵巢组织中的表达强度。结果：PCOS组卵巢组织中抑制素B的浓度高于对照组,差异有显著性。结论：抑制素B参与了PCOS患者的性激素分泌失调。检测与调节PCOS患者中抑制素B的水平可能有助于指导PCOS的治疗。     

胆囊功能CCK及其受体与结石成因关系之研究

本文用B超对24例胆囊结石患者进行胆囊功能各方面的研究,并对照血浆中胆囊收缩素(CCK)浓度与胆囊壁CCK受体(CCK-R)数目,以进一步探讨胆囊功能改变在胆囊结石发病中的意义。结果发现14例胆囊收缩率“正常组”患者:空腹胆囊体积增大,正常的餐后CCK血浓度,而10例胆囊收缩率“降低组”患者;胆囊残留体积增大,餐后CCK血浓度明显高于正常组。胆囊壁CCK-R结合位点数胆囊收缩率“正常组”明显多于胆囊收缩率“降低组”,胆囊收缩性的差异与CCK-R数有关。揭示了二组胆囊结石患者产生结石的某些过程和机制的不同点及最终形成结石的胆囊功能基础。     

电针对去卵巢大鼠脑内雌激素受体mRNA的影响

目的探讨雌激素降低对脑内雌激素受体基因表达的影响以及电针刺激足三里穴对去卵巢大鼠脑内雌激素受体基因表达的调整作用。方法选用成年Wistar雌性大鼠，将动物分为正常对照组（INT）、去卵巢组（OVX）和去卵巢针刺组（OVX＋EA）。用放射免疫分析方法测定血中雌二醇和睾酮的含量，采用RT-PCR方法获得大鼠雌激素受体α（ERα）和雌激素受体β（ERβ）mRNA的逆转录表达产物cDNA，用琼脂糖凝胶电泳方法检测，计算机图像分析系统进行统计分析。结果与对照组比较，去卵巢组大鼠血中雌二醇水平明显降低（P〈0．01），同时伴有睾酮升高，脑内ERα mRNA的RT-PCR表达产物减少（P〈0．01），ERβ mRNA的RT—PCR表达产物增加（P〈0．01）；与去卵巢组相比，去卵巢针刺组大鼠血中雌激素水平明显升高（P〈0．01），睾酮水平下降（P〈0．01），脑内ERα mRNA的RT-PCR产物升高（P〈0．01），ERβ mRNA的RT—PCR产物降低（P〈0．01）。结论去卵巢大鼠血中雌激素水平降低，睾酮水平升高，脑内ERα和ERβ mRNA的表达发生了明显的变化；电针足三里穴对体内雌激素和睾酮水平及脑内雌激素受体基因表达有明显的调整作用，这可能是电针调节神经内分泌功能的机制之一。     

头孢曲松钠对豚鼠胆囊收缩功能影响的实验研究

目的研究头孢曲松钠对豚鼠胆囊收缩功能的影响,以更好地指导临床用药。方法将60只豚鼠随机分为四组,A组(空腹对照组)、B组(饱餐对照组)、C组(空腹实验组)和D组(饱餐实验组)。对实验组C组、D组肌肉注射头孢曲松钠,建立头孢曲松钠相关性胆囊模型。造模成功后,对四组豚鼠的胆囊体积、胆汁量、胆汁及血清中胆汁酸、丙氨酸氨基转移酶(ALT)及胆囊收缩素(CCK)含量及胆囊组织中胆囊收缩素A受体(CCK-AR)基因的表达等进行测定。结果 C组和饱餐实验组的胆囊体积均显著高于A组和B组,表明头孢曲松钠可显著增高豚鼠的胆囊体积(P0.05);实验组豚鼠的胆汁量均显著高于对照组(P0.05),表明实验组豚鼠胆囊内出现胆汁淤积。胆汁中实验组豚鼠的胆汁酸水平均显著低于对照组;而血清中实验组豚鼠的胆汁酸水平均显著高于对照组(P0.05),表明实验组胆汁中胆汁酸的浓度出现下降,而血清中胆汁酸的含量则呈上升趋势。实验组豚鼠的ALT含量显著高于对照组豚鼠,表明头孢曲松钠可致豚鼠ALT水平升高。血清及胆囊组织中实验组的CCK水平均显著低于对照组;实验组胆囊组织中CCK-AR mRNA的相对表达量均显著低于对照组(P0.05)。结论头孢曲松钠可降低血清及胆囊组织中CCK的含量,并抑制CCK受体基因的表达,从而减弱胆囊的收缩功能,导致胆囊内出现胆汁淤积,促进结石的形成。为减少此类不良反应的发生,临床上应尽量避免长期、大剂量的使用头孢曲松钠。     

液相色谱串联质谱测定大鼠血浆中多黏菌素E甲磺酸钠及多黏菌素E方法的建立及应用

目的 建立液相色谱串联质谱（LC-MS/MS）法测定大鼠血浆中多黏菌素E甲磺酸钠（CMS）及其活性成分多黏菌素E并进行应用。方法 通过多黏菌素E主成分E1及E2浓度之和间接得到多黏菌素E的浓度。在大鼠血浆样品中加入硫酸对CMS进行水解，通过测定水解后与水解前血浆样品中多黏菌素E的浓度差间接测定CMS浓度。采用固相萃取法对样品进行预处理。色谱柱选择Phonomenex Kinetex XB-C18柱，质谱采用电喷雾电离源（ESI源）及多反应监测（multi-reaction monitoring,MRM）模式。其中待测物质多黏菌素E1、多黏菌素E2、内标多黏菌素B1的离子通道分别为m/z390.7→101.3、m/z 386.0→101.2、m/z 402.3→101.2。结果 多黏菌素E1及E2的测定不受大鼠血浆中内源物质的影响，且分别在0.187～6.24 mg/L、0.037 0～1.23 mg/L内线性良好，批内与批间精密度良好，变异系数均<15%。多黏菌素E1、E2准确度范围分别为100.1%～113.3%和94.9%～107.3%。多黏菌素E1、E2的提取回收率分别为2...     

Effects of a novel cholecystokinin (CCK) receptor antagonist, MK-329, on gallbladder contraction and gastric emptying in humans. Implications for the physiology of CCK.

To explore the physiology of cholecystokinin (CCK) in humans, we investigated the effect on gallbladder contraction and gastric emptying of a recently developed CCK receptor antagonist, MK-329. In a double-blind, four-period crossover study eight subjects received single doses of 0.5, 2, or 10 mg MK-329, or placebo, followed by an intravenous infusion of CCK-8 (30 pmol/kg.h). In placebo-treated subjects gallbladder volumes decreased on average to 43% of initial volumes after 2 h of CCK infusion. MK-329 caused a dose-dependent inhibition of CCK-stimulated gallbladder contraction with 10 mg producing complete blockade (P less than 0.01, cf. placebo). Gallbladder contraction and gastric emptying rates after a mixed meal were then measured in a two-period crossover study. Subjects received placebo or 10 mg of MK-329 2 h before eating. Gastric emptying of both solids and liquids was measured simultaneously by gamma scintigraphy. In placebo-treated subjects plasma CCK levels increased postprandially to 2.3 pM, gallbladder volumes decreased 68.4 +/- 3.8% (SE), and the times for 50% emptying of liquids and solids from the stomach were 58 +/- 10 and 128 +/- 8 min, respectively. In MK-329-treated subjects there was a marked elevation in peak CCK levels to 13.8 pM (P less than 0.01, cf. placebo), and gallbladder contraction was completely inhibited. Solid and liquid emptying rates were unaffected. These findings demonstrate that (a) MK-329 is a potent, orally active antagonist of CCK in humans, and (b) CCK is the major regulator of postprandial gallbladder contraction. These data also support the concept of negative feedback regulation of CCK secretion and suggest that mechanisms other than CCK play a dominant role in the regulation of postprandial gastric emptying rates.     

In vivo pharmacology of L-364,718, a new potent nonpeptide peripheral cholecystokinin antagonist

The in vivo pharmacological activity of L-364,718, a new, potent peripheral cholecystokinin (CCK) antagonist, was characterized in several species using assay systems that measure various well known actions of CCK upon the gastrointestinal system. Administered p.o., L-364,178 was highly potent in antagonizing cholecystokinin octapeptide (CCK-8)-induced inhibition of gastric emptying in mice (ED50 = 38 micrograms/kg), rats (ED50 = 140 micrograms/kg) and dogs (ED50 = 91 micrograms/kg) as well as CCK-8-induced reduction in food consumption in rats (ED50 = 321 micrograms/kg). Administered i.v., L-364,718 effectively antagonized the contractile effects of CCK on the colon in rabbits (ED50 = 34 micrograms/kg) and the gallbladder in cats (ED50 = 210 micrograms/kg). Secretion of pancreatic protein and amylase elicited by CCK in cats was also antagonized by L-364,718 (ED50 less than 1.0 mg/kg i.v.). The CCK antagonism produced by L-364,718 in all species persisted for at least 2 to 5 hr. In the absence of exogenously administered CCK-8, L-364,718 per se had no effect in any of the assay systems studied, indicating a lack of CCK-like agonist properties. Specificity for CCK was demonstrated by the inability of L-364,718 (1.0-5.0 mg/kg) to antagonize either amino acid- or atropine-induced inhibition of gastric emptying in rats and dogs, respectively. L-364,718 also did not antagonize motilin-induced gallbladder contractions or secretin-induced pancreatic secretion in cats.(ABSTRACT TRUNCATED AT 250 WORDS)     

Regulation of gastric emptying in humans by cholecystokinin.

In the present study we used a bioassay system for measuring plasma cholecystokinin (CCK) to evaluate whether CCK has a physiologic role in regulating gastric emptying in humans. Plasma CCK levels and gastric emptying after ingestion of a mixed liquid meal were determined in five normal male volunteers. Fasting CCK levels averaged 0.8 +/- 0.1 pM and increased to 6.5 +/- 1.0 pM within 10 min of drinking the mixed meal. CCK levels remained elevated for up to 90 min. Gastric emptying after a meal was slow; at the end of the 90 min 68% of the original volume remained in the stomach. The rate of gastric emptying of water was then measured in the same individuals with a simultaneous infusion of either saline, or one of two doses of CCK (12 pmol/kg per h and 24 pmol/kg per h). With the saline infusion, plasma CCK levels did not increase above basal and gastric contents emptied rapidly. At the end of 90 min only 7% of the original volume remained in the stomach. The lower dose of CCK resulted in a plasma level of 3.4 pM which both reproduced the average postprandial plasma level and caused a significant delay in gastric emptying. The higher dose of CCK achieved plasma levels of 8 pM and resulted in a delay in gastric emptying that was similar to that seen with the mixed meal. Since exogenous CCK at concentrations which occur postprandially delays gastric emptying, we conclude that CCK is a physiologic regulator of gastric emptying.     

Role of the gastric phase in fat-induced gallbladder contraction and cholecystokinin secretion in humans

The present study was undertaken to investigate the role of the gastric phase of fat-induced gallbladder contraction and endogenous cholecystokinin (CCK) secretion in humans. Gallbladder emptying, measured by cholescintigraphy, and endogenous CCK secretion, measured by radioimmunoassay, were studied in healthy subjects after both intragastric and intra-intestinal administration of corn oil. In addition, patients with partial gastrectomy were investigated to study the effect of accelerated gastric emptying. In the healthy subjects, intragastric administration of fat resulted in a significantly (P less than 0.05) later increase in plasma CCK levels (20 +/- 2 min) compared to intraintestinal fat (5 +/- 1 min). Similarly, the onset of gallbladder emptying was significantly (P less than 0.05) delayed after intragastric fat (20 +/- 2 min) compared to intestinal fat (10 +/- 1 min). In the healthy subjects the integrated plasma CCK response to intragastric fat was significantly (P less than 0.005-P less than 0.01) reduced from 10 to 30 min. In the patients with partial gastrectomy the rise in plasma CCK (10 +/- 1 min) and the onset of gallbladder emptying (15 +/- 2 min) were in the same range after intra-intestinal and intragastric fat. No significant differences in plasma CCK levels, integrated CCK response or gallbladder emptying were found in the patients according to the site of fat application. It is concluded that endogenous CCK secretion and gallbladder emptying in response to intragastric fat are significantly delayed in healthy subjects but not in patients with partial gastrectomy, in whom gastric emptying is accelerated.(ABSTRACT TRUNCATED AT 250 WORDS)     

Physiological role for cholecystokinin in reducing postprandial hyperglycemia in humans.

It is known that the ingestion of glucose alone causes a greater increase in plasma glucose levels than ingestion of the same amount of glucose given with other nutrients. Since physiological plasma concentrations of cholecystokinin (CCK) prolong gastric emptying, it is proposed that after a meal, CCK may modify plasma glucose levels by delaying glucose delivery to the duodenum. To evaluate the effect of CCK on oral glucose tolerance, plasma CCK, insulin, and glucose levels and gastric emptying rates were measured in eight normal males before and after the ingestion of 60 g glucose with the simultaneous infusion of either saline or one of two doses of CCK-8 (12 or 24 pmol/kg per h). Gastric emptying rates were measured by gamma camera scintigraphy of technetium 99m sulfur colloid and plasma CCK levels were measured by a sensitive and specific bioassay. Basal CCK levels averaged 1.0 +/- 0.1 pM (mean +/- SEM, n = 8) and increased to 7.1 +/- 1.1 pM after a mixed liquid meal. After glucose ingestion, but without CCK infusion, CCK levels did not change from basal, and the gastric emptying t1/2 was 68 +/- 3 min. Plasma glucose levels increased from basal levels of 91 +/- 3.9 mg/dl to peak levels of 162 +/- 11 mg/dl and insulin levels increased from 10.7 +/- 1.8 microU/ml to peak levels of 58 +/- 11 microU/ml. After glucose ingestion, with CCK infused at 24 pmol/kg per h, plasma CCK levels increased to 8 pM and the gastric emptying t1/2 increased to 148 +/- 16 min. In concert with this delay in gastric emptying, peak glucose levels rose to only 129 +/- 17 mg% and peak insulin levels rose to only 24.2 +/- 4.2 microU/ml. With CCK at 12 pmol/kg per h, similar but less dramatic changes were seen. To demonstrate that endogenous CCK could modify the plasma glucose and insulin responses to oral glucose, oral glucose was given with 50 g of lipid containing long-chain triglycerides. This lipid increased peak CCK levels to 3.7 +/- 0.9 pM. Concomitant with this rise in CCK was a delay in gastric emptying and a lowering of plasma glucose and insulin values. To confirm that CCK reduced hyperglycemia by its effect on gastric motility, 36 g glucose was perfused directly into the duodenum through a nasal-duodenal feeding tube in four subjects. With duodenal perfusion of glucose, there was no change in plasma CCK levels, but plasma glucose levels increased from basal levels of 93+/-5 to 148+/-6 mg/dl and insulin levels rose from 10.6+/-3.5 to 29.5+/-5.2 microU/ml. When CCK was infused at 24 pmol/kg per h, neither the plasma glucose nor insulin responses to the duodenal administration of glucose were modified. Thus we conclude that CCK, in physiological concentrations, delays gastric emptying, slows the delivery of glucose to the duodenum, and reduces postprandial hyperglycemia. These data indicate, therefore, that CCK has a significant role in regulating glucose homeostasis in human.     

Fasting and nutrient-stimulated plasma peptide-YY levels are elevated in critical illness and associated with feed intolerance: an observational, controlled study

Introduction  

Delayed gastric emptying and feed intolerance occur frequently in the critically ill. In these patients, gastric motor responses to nutrients are disturbed. Peptide YY (PYY) slows gastric emptying. The aim of this study was to determine fasting and nutrient-stimulated plasma PYY concentrations and their relationship to cholecystokinin (CCK) in critically ill patients.     

SREBP-2 regulates gut peptide secretion through intestinal bitter taste receptor signaling in mice

Bitter taste-sensing G protein-coupled receptors (type 2 taste receptors [T2Rs]) are expressed in taste receptor cells of the tongue, where they play an important role in limiting ingestion of bitter-tasting, potentially toxic compounds. T2Rs are also expressed in gut-derived enteroendocrine cells, where they have also been hypothesized to play a role in limiting toxin absorption. In this study, we have shown that T2R gene expression in both cultured mouse enteroendocrine cells and mouse intestine is regulated by the cholesterol-sensitive SREBP-2. In addition, T2R stimulation of cholecystokinin (CCK) secretion was enhanced directly by SREBP-2 in cultured cells and in mice fed chow supplemented with lovastatin and ezetimibe (L/E) to decrease dietary sterol absorption and increase nuclear activity of SREBP-2. Low-cholesterol diets are naturally composed of high amounts of plant matter that is likely to contain dietary toxins, and CCK is known to improve dietary absorption of fats, slow gastric emptying, and decrease food intake. Thus, these studies suggest that SREBP-2 activation of bitter signaling receptors in the intestine may sensitize the gut to a low-fat diet and to potential accompanying food-borne toxins that make it past the initial aversive response in the mouth.     

Estrogen alters spinal NMDA receptor activity via a PKA signaling pathway in a visceral pain model in the rat

Pain symptoms in several chronic pain disorders in women, including irritable bowel syndrome, fluctuate with the menstrual cycle suggesting a gonadal hormone component. In female rats, estrogens modulate visceral sensitivity although the underlying mechanism(s) are unknown. In the present study the effects of 17-β estradiol on N-methyl-d-aspartate (NMDA) receptor signaling of colorectal nociceptive processing in the spinal cord were examined. Estrogen receptor alpha and the NR1 subunit of the NMDA receptor are co-expressed in dorsal horn neurons, supporting a direct action of estradiol on NMDA receptors. Intrathecal administration of the NMDA receptor antagonist d(−)-2-amino-5-phosphonopentanoic acid (APV) dose-dependently attenuated the visceromotor response with greater potency in ovariectomized (OVx) rats compared to OVx with estradiol replacement (E2) rats. Estradiol significantly increased protein expression of NR1 in the lumbosacral spinal cord compared to OVx rats. Colorectal distention significantly increased phosphorylation of NR1ser-897, a PKA phosphorylation site on the NR1 subunit in E2, but not OVx rats. Intrathecal administration of a PKA inhibitor significantly attenuated the visceromotor response, decreased NR1 phosphorylation and increased the potency of APV to attenuate the visceromotor response compared to vehicle-treated E2 rats. These data suggest that estradiol increases spinal processing of visceral nociception by increasing NMDA receptor NR1 subunit expression and increasing site-specific receptor phosphorylation on the NR1 subunit contributing to an increase in NMDA receptor activity.     

糖尿病大鼠瘦素和下丘脑瘦素功能受体的表达与胃排空的关系

目的探讨糖尿病不同阶段胃排空障碍与血清瘦素及其下丘脑OB-Rb表达的关系。方法40只Wistar大鼠随机分为对照饲养1周组（NC1组；n=6）、对照饲养4周组（NC2组；n=6）、糖尿病造模1周组（DM1组；n=14）和糖尿病造模4周组（DM2组；n=14）。分别于给药后1周、4周用酚红灌胃法检测胃排空；用放射免疫法、半定量RT—PCR技术检测大鼠血清瘦素及其下丘脑OB-Rb mRNA的表达。结果注射STZ1周后，DM1组大鼠血清瘦素明显低于NC1组（P〈0．05）；下丘脑OB-Rb mRNA表达明显低于NC1组；液体胃排空是加快的（P〈0．01）。注射STZ4周后，DM2组大鼠血清瘦素和胃排空明显低于NC2组（P〈0．05；P〈0．01）；DM2组下丘脑组织OB—Rb mRNA的表达明显高于NC2组（P〈0．05）。结论Ⅰ型糖尿病早期，机体可能通过降低血清瘦素和反应性的下调下丘脑OB-Rb表达，以加快胃排空。维持能量平衡。而长期高血糖及低瘦素水平可能反馈性的引起下丘脑OB-Rb表达上调，参与胃排空延迟。     

Roles of endogenous cholecystokinin in biliary, pancreatic and gastric function: studies with L-364,718, a specific cholecystokinin receptor antagonist

A new, highly potent antagonist of gut cholecystokinin (CCK) receptors has been examined for effects upon postprandial biliary and exocrine pancreatic secretion in conscious dogs with chronic duodenal pouches. This drug (L-364,718) markedly inhibited the postprandial increases in biliary volume, bile acid and bilirubin secretion. However, even at high p.o. doses relative to its ability to antagonize the effects of exogenous CCK, no effects were observed upon the pancreatic secretion of either fluid volume or amylase and lipase under similar conditions. In additional studies, pretreatment with L-364,718 did not significantly reverse the inhibitory effects of a fatty acid salt (sodium oleate) upon gastric emptying in gastric fistula dogs. Moreover, pretreatment with L-364,718 had no significant effects upon postprandial acid and pepsin secretion in lesser curvature (vagally innervated) pouch dogs or did it affect basal (interdigestive) gastric secretion in rats. These results suggest that endogenous CCK plays a critical physiological role in regulating postprandial biliary outflow, but not pancreatic enzyme secretion or the gastric emptying of at least liquid fatty substances. The latter two findings stand in contrast with classical views regarding the physiological function(s) of this hormone.