胆囊收缩素（CCK8）对实验性神经细胞老化过程中脂褐素的影响

目的 观察CCK8对实验性神经细胞老化过程中脂褐素的影响。方法采用小鼠神经母细胞瘤细胞（NBA2）无血清培养建立神经细胞老化实验研究模型。以显微荧光分光光度术测定单个细胞内脂褐素自发荧光值作为细胞的老化指标，观察CCK8对这些指标的影响。结果在无血清培养条件下，细胞内脂褐素荧光值随培养时间的延长而累积性增加（P<0.01）。将CCK8加入无血清培养液，CCK8作用10天和15天都可显降低细胞内脂褐素荧光值（P<0.01）。结论在无血清培养条件下，NBA2细胞由分裂增殖变为分化成熟老化，反映了神经细胞的老化过程，而CCK8可延缓细胞的老化过程。     

胆囊收缩素对实验性神经细胞老化过程中微突起影响的超微结构研究

目的　探讨胆囊收缩素 (CCK8)对实验性神经细胞老化过程中细胞微突起超微结构的影响。方法　采用 NBA2 细胞无血清培养建立神经细胞老化实验模型。以扫描电子显微镜观察的细胞表面结节状物的大小以及微突起数目作为细胞老化指标 ,观察 CCK8对细胞老化过程的影响。结果　 1使细胞表面结节状物变小。 2增加细胞突起终末的微突起数量。结论　 CCK8可以延缓实验性神经细胞的老化进程值得进一步研究。     

胆囊收缩素与神经细胞老化

胆囊收缩素(CCK)不仅是体内重要的胃肠激素，而且是脑内含量最丰富、分布最广泛的神经递质，在调节进食、情绪和神经内分泌、疼痛、学习记忆等发挥重要作用。同时，在中枢神经系统它与其他神经递质共存，共同调节机体活动。CCK在提高认知、空间、学习、记忆功能，延缓其减退的进程中的作用引起广泛地关注。     

胆囊收缩素对功能性消化不良患者固体胃排空的影响

目前公认胆囊收缩素（ＣＣＫ）对胃运动调节具有生理性意义,我们用核素法观察ＣＣＫ对功能性消化不良（ＦＤ）患者团体胃排空的影响。 一、资料与方法 １．对象：对照组１５例,男１１例,女４例,年龄２３～５８岁,平均年龄２９岁,均无消化系统疾病及胃肠道症状;无腹部手术史。ＦＤ组２８例,男２３例,女５例,年龄２５～５４岁,平均３２岁。诊断标准：（ｌ）消化不良症状至少存在６个月以上,有典型早饱及上腹胀满;（２）经胃镜、Ｘ线、Ｂ超及其他辅助检查排除器质性疾病;（３）排除有胃肠道手术、神经精神疾病、代谢性疾病史。受…     

针刺后胆囊收缩素对肥胖大鼠能量代谢的影响

目的 观察肥胖大鼠针刺后胆囊收缩素(cholecystokinin,CCK)对其能量代谢的影响.方法 应用谷氨酸钠制作肥胖动物模型,分为模型组、针刺组并设正常对照组(对照组),采用放免分析法检测其下丘脑和血液CCK含量和血清血脂水平和脂蛋白脂酶(LPL)活性.结果 针刺后针刺组血浆、下丘脑CCK含量均高于模型组(P＜0.05,P＜0.01);针刺组体重指数(Lee)指数、肾周和大网膜脂肪均较模型组明显下降(P＜0.01),血脂各项呈不同程度改变.结论 针刺可刺激肥胖大鼠下丘脑和血浆中CCK含量升高,此效应可能参与中枢脂代谢水平和加强胃肠功能活动.     

胆囊收缩素对胃蛋白酶原和胃酸分泌的影响

胆囊收缩素(CCK)广泛分布于胃肠道和神经系统,对胃蛋白酶原(PG)和胃酸分泌具有双重影响。体外研究表明CCK由主细胞、壁细胞上相应受体介导促进PG和胃酸的分泌;在体内CCK通过某种途径(如刺激D细胞释放生长抑素)间接抑制PG和胃酸的分泌。CCK对PG和胃酸分泌具有生理性调节作用。十二指肠溃疡患者CCK抑酸机制可能有缺陷。     

胆囊收缩素对胃蛋白酶原和胃酸分泌的影响

胆囊收缩素广泛分布于胃肠道和神经系统，对胃蛋白酶原和胃酸分泌具有双重影响。体外研究表明ＣＣＫ由主细胞、壁细胞上相应受体介导促进ＰＧ和胃酸的分泌；在体内ＣＣＫ通过某种途径间接抑制ＰＧ和胃酸的分泌。     

胆囊收缩素对消化道运动调节作用的研究进展

胆囊收缩素(Cholecystokinin,CCK)是被研究较为广泛的胃肠激素之一,它广泛存在于体内许多部位,是一种具有广泛生物学活性的脑肠肽。随着对CCK及其受体亚型分子生物学的认识和其拮抗剂的发展,其生理作用的研究已趋深入。CCK不仅能刺激胆囊收缩,而且对整个胃肠运动的调控起着重要作用。本文就其对胃肠电活动及全消化道运动的调节作用综述如下。     

胆囊收缩素对脂多糖刺激大鼠肺泡巨噬细胞的影响

八肽胆囊收缩素（CCK-8）对内毒素休克（ES）大鼠有保护作用,可能与抑制ES大鼠促炎性细胞因子过量生成有关.CCK-8可能与CCK受体结合干扰脂多糖（LPS）诱导肺泡巨噬细胞（AM）过度激活.     

Effect of cholecystokinin on experimental neuronal aging

AIM: To observe the effect of cholecystokinin (CCK) on lipofusin value, neuronal dendrite and spine ultrastructure, and total cellular protein during the process of experimental neuronal aging. METHODS: Experimental neuronal aging study model was established by NBA2 cellular serum-free culture method. By using single intracellular lipofusin value from microspectrophotometry, morphology of neuronal dendrites and spines from the scanner electron microscopy, and total cellular protein as the indexes of experimental neuronal aging, we observed the effect of CCKs on the process of experimental neuronal aging. RESULTS: Under the condition of serum-free culture, intracellular fluorescence value (%) increased with the extension of culture time (1 d 8.51±3.43; 5 d 10.12±3.03; 10 d 20.54±10.3; 15 d 36.88±10.49; bP<0.01). When CCK was added to serum-free culture medium, intracellular lipofusin value (%) decreased remarkably after consecutive CCK reaction for 10 and 15 d (control 36.88±10.49; 5 d 32.03±10.01; 10 d 14.37±5.55; 15 d 17.31±4.80; bP<0.01). As the time of serum-free culturing was prolonged, the number of neuronal dendrite and spine cells decreased. The later increased in number when CCK8 was added. CCK8 could improve the total cellular protein in the process of experimental neuronal aging. CONCLUSION: CCKs may prolong the process of experimental neuronal aging by maintaining the structure and the number of neuronal dendrite and spine cells and changing the total cellular protein.     

强啡肽对实验性神经细胞老化过程中M胆碱能受体位点数影响的研究

目的　探讨强啡肽 (DYN)对实验性神经细胞 M受体位点数的影响。方法　采用小鼠神经母细胞瘤细胞 (NBA2 )无血清培养建立神经细胞老化实验研究模型。以 M受体放射性配基分析术研究 DYN对实验性神经细胞的 M受体位点数的影响。结果　两种不同浓度的 DYN皆可使M受体位点数下降 (P<0 .0 1 ) ,以高浓度组更显著。结论　 DYN使 M受体位点数下降的作用可能是延缓实验性神经细胞老化的机制之一。(最终浓度为 0 .1nmol/L) ,以测定非特异性结合。各管加入2 0 0 μl膜蛋白液 ,37℃振荡温育 4 0 min。冰冷缓冲液终止反应。6 9型纤维滤膜三层抽滤并淋洗 ,滤膜烘干 ,投入 5 ml闪烁液(含 0 .4 % PPO的三甲苯 )中 ,以 YSL- 76型液闪计数器做固相测定。1.8　 数据处理　实验得到特异性结合的技术率 ,被测定效率除 ,等于特异性结合衰变率 ,再除以放射性配基活度 ,即等于特异性结合位点数〔7〕。采用 POMS方差分析 ,经 IBM微机处理数据。2　结果与讨论DYN对 NBA2 细胞 M胆碱能受体位点数的影响 ,见表 1。表 1　 DYN对 M受体位点数的影响 (nmol/10 6 细胞 )组别 n M受体位点数 (x± s)BSD组 5 449.796± 356.730AID组 5 486.941± 2 4 7.1 65DYN- 7组 5 1 4 5.71 4± 77.82 61 )DYN- 8组 5 1 51 .873± 95.80 61 )　　注 :DY     

血管活性肠肽对神经细胞脂褐素影响的实验研究

采用小鼠神经母细胞癌细胞无血清培养建立神经细胞老化实验研究模型。以显微荧光分光光度术测定的细胞内脂褐素自发荧光值为神经细胞老化指标，观察血管活性肠肽（ＶＩＰ）对实验性神经细胞内脂褐素荧光值的影响。结果发现：ＶＩＰ作用５ｄ可显著升高细胞内的脂褐素荧光值（Ｐ＜０．０１）．提示ＶＩＰ可加速实验性神经细胞的老化过程。     

胆囊收缩素在应激时胆汁反流中的作用及其相关机制

目的证实应激过程中胆汁反流的存在,探讨胆囊收缩素八肽(CCK-8)在应激所致胆汁反流中的作用及相关机制。方法放免法检测大鼠血浆 CCK-8和胃液胆汁酸水平,测定胃液 pH值并记录胃黏膜溃疡指数;多导生理记录仪记录离体肌条收缩活动;检测 Fura-2/AM 标记的胃窦平滑肌细胞(SMC)内钙离子浓度([Ca~(2+)]i)的变化;全细胞膜片钳记录 L-型钙通道电流(I_(Ca-L))。结果与正常对照相比,应激时血浆 CCK-8[从(2.23±0.88)pmol/L 到(10.80±3.82)pmol/L],胃液胆汁酸[从(37.93±23.76)μmol/L 到(1316.00±197.36)μmol/L],pH 值(从1.06±1.20到5.29±1.25)和溃疡指数(从0.62±0.23到32.01±16.11)均明显增高(P<0.01);CCK-8S 显著增强胃窦和幽门肌条收缩和胃窦 SMC 的[Ca~(2+)]i[从(65.8±7.4)nmol/L 升至(472.1±35.6)nmol/L,P<0.01]及 I_(Ca-L)[从(-56.42±6.57)pA 增至(-88.54±5.71)pA,P<0.01],但可被相应拮抗剂所抑制。结论与应激时 CCK-8升高所致的胃窦动力紊乱相关,胆汁反流存在于应激过程中,是应激性胃黏膜损伤的重要因素。     

Effect of a new cholecystokinin antagonist (FK 480) on gene expression of cholecystokinin and secretin in rat intestine

The effects of a new cholecystokinin (CCK) antagonist (FK 480; 0.1 mg/kg per day given by intragastric administration to rats for 3 days) on the expression of the CCK and secretin genes, plasma CCK immunoreactivity, and CCK content in the intestinal mucosa were examined. FK 480 increased the level of CCK mRNA in the intestine to 1.7 times the level in control rats, but did not affect the level of secretin mRNA. It did not increase plasma CCK immunoreactivity or CCK content in the intestinal mucosa. These results suggest that the ingested FK 480 directly increased CCK mRNA level in the intestine and produced a dissociation between the synthesis and release of CCK.     

Effect of a cholecystokinin receptor antagonist (loxiglumide) on gallbladder contractile function in guinea pigs

We evaluated the effect of the specific cholecystokinin (CCK) receptor antagonist, loxiglumide, on gallbladder contractile function in guinea pigs. Five mg/kg body weight (BW) of loxiglumide was administered orally to guinea pigs once a day for 3 days. We then investigated gallbladder contractile function and plasma CCK concentrations in the guinea pigs. Maximal gallbladder pressure induced by cerulein was significantly depressed on the 1st and 3rd days following loxiglumide administration. On the 1st day, the plasma CCK concentration was significantly increased compared with that of the control group during fasting and 15 min after the administration of an intraduodenal test meal. These results suggest that the disturbed gallbladder contraction is due to the competitive inhibition of CCK by loxiglumide. Gallbladder contractile function in guinea pigs is depressed by loxiglumide; however, this effect is reversible after short-term loxiglumide administration.     

胆囊收缩素对豚鼠近端结肠平滑肌的作用及其机制

目的 通过记录胆囊收缩素(CCK)对近端结肠平滑肌条和平滑肌细胞膜离子通道电流的影响,研究其对结肠动力的影响及其在肠易激综合征(IBS)发病中可能存在的病理机制.方法 成年豚鼠(200～250 g)实验前禁食12 h,不禁水.处死动物取近端结肠约6 cm,记录离体近端结肠肌条在浓度为1×10-7、5×10-7、1×10-6mol/L的胆囊收缩素八肽(CCK-8)作用下的张力和收缩频率变化;用EPC-10膜片钳和图像分析软件系统检测1×10-7、5×10-7、1×10-6 mol/L CCK-8及经尼非地平预处理的1×10-6mol/L CCK-8对近端结肠平滑肌细胞钙依赖钾通道电流(1BKca)的影响.结果 结肠平滑肌肌条实验中,分别加入1×10-7、5×10-7、1×10-6mol/L CCK-8后正常的收缩活动明显增强,与加药前[(0.68±0.12)g]相比,收缩幅度分别增加(15.0±1.5)%、(28.0±1.4)%和(36.0±1.6)%(n=7,P值分别=0.023、0.005和0.001),但频率变化不明显.膜片钳实验中,当越阶刺激为+60 mV时加入1×10-7、5×10-7、1×10-6mol/LCCK-8,此时IBKCa电流分别为对照组的(117.45±3.60)%、(125.42±5.30)%和(136.98±6.80)%(n=7,P值均＜0.01).预先加入尼非地平后,1×10-6mol/L CCK-8组+60 mV时IBKca为对照组的(102.23±5.60)%(n=7,P=1.491).结论 CCK通过促进Ca2+内流,增加Ibkca,进而增强结肠平滑肌的运动,主要表现为收缩幅度的加快.

Abstract：

Objective To investigate the effect of cholecystokinin (CCK) on colon motility and its mechanism in development of irritable bowel syndrome via recording ionic channels currents and contraction of guinea-pig proximal colon. Methods The guinea-pigs (body weight ranged from 200 g to 250 g) were deprived of food, but not water, for 12 hours before experiment. The animal was sacrificed and 6 cm of proximal colon was obtained. The contractile activity of isolated proximal colon in 1 × 10-7 ,5 × 10-7 or 1 × 10-6 mol/L of CCK-8 solution was recorded. The impact of 1 × 10-7 , 5 × 10-7 and 1 × 10-6 mol/L of CCK-8 and 1 × 10-6 mol/L CCK-8 nifidipin on current of calcium activated potassium channel (IBKac) was detected with an EPC-10 amplifier and an image analysis software.Results In comparison with blank [(0. 68 ±0. 12) g], the amplitude of colon contraction in 1 × 10-7 ,5×10-7 and 1×10-6 mol/L of CCK-8 was increased by (15. 0±1.5)%,(28. 0±1.4)%, and (36.0±1.6) %, respectively ( n = 7, P = 0. 023,0. 005 and 0. 01 ), but there was no significant change of frequency. When exogenous stimulation at +60 mV, the current of IBKac was enhanced to (117. 45 ± 3.60)%, (125.42± 5. 30)% or (136. 98±6. 80)% in 10-7 ,5 × 10-7 or 10-6 mol/L of CCK-8,respectively, compared with controls (n= 7, P＜0.01 ). However, after adding nifidipin, the current of IBKca was reduced to (102.23±5.60)% in 10-6mol/L of CCK-8 at +60 mV when compared with controls (n=7, P= 1. 491 ). Conclusion CCK enhances proximal colonic motility by increasing Ca2+ influx and IBKac current, which is characterized by enhancement of amplitude of contraction.     

Effect of dehydroepiandrosterone (DHEA) on monoamine oxidase activity,lipid peroxidation and lipofuscin accumulation in aging rat brain regions

Dehydroepiandrosterone (DHEA), one of the major steroid hormones, and its ester have recently received attention with regard to aging and age-related diseases like Alzheimer and others. DHEA is synthesized de novo in the brain and its substantial fall with age has been shown to be associated with neuronal vulnerability to neurotoxicity processes. Thus, DHEA is considered to be a neuroactive pharmacological substance with potential antiaging properties. A prominent feature that accompanies aging is an increase in monoamine oxidase (MAO). Increased MAO activity with correlated increase in lipid peroxidation in the aging rat brain supports the hypothesis that catecholamine oxidation is an important source of oxidative stress. The progressive accumulation of lipofuscin in neuronal cells is one of the most characteristic age related changes, an increase in body weight was also observed at 24 months. The objective of this study was to observe the changes in monoamine oxidase activity, lipid peroxidation levels and lipofuscin accumulation occurring in aging rat brain regions, and to see whether these changes are restored to normal levels after exogenous administration of DHEA (30 mg/kg/day for 1 month). The results obtained in the present work revealed that normal aging was associated with significant increases in the activity of monoamine oxidase, lipid peroxidation levels and lipofuscin accumulation in brain regions of 4, 14 and 24 months age group male rats. The present study showed that DHEA treatment significantly decreased monoamine oxidase activity, lipid peroxidation and lipofuscin accumulation in brain regions of aging rats, the increased body weight at 24 months also decreased more than the age matched controls. It can therefore be suggested that DHEA's beneficial effects seemed to arise from its antioxidant, antiobesity, antilipofuscin, antilipidperoxidative and thereby anti-aging actions. The results of this study will be useful for pharmacological modification of the aging process and development of new drugs for age related disorders.     

The changes in the rat parotid glands following total parenteral nutrition and pancreatico-biliary diversion are not mediated by cholecystokinin

Summary Conclusions The results of the present study suggest that the pancreas and parotid glands both respond with hypoplasia during absence of food in the digestive tract and with hyperplasia following pancreactico-biliary diversion (PBD). Factors other than cholecystokinin (CCK) are, however, involved in the effects on the parotid glands, since infusion of CCK-8S and devazepide was without influence. Background and Aim Total parenteral nutrition (TPN) causes reduced pancreatic weight, whereas PBD evokes hyperCCKemia and enlargement of the rat pancreas. The pancreas and parotid glands have in part similar morphology and function. Therefore, we studied the possible presence of alterations also in the parotid glands during TPN, after PBD and during infusion of sulfated cholecystokinin (CCK-8S) and the CCK-A receptor antagonist devazepide, respectively. Materials and Results Rats either received TPN for 7 d, or were kept under otherwise identical conditions with free access to food and water. TPN markedly reduced both pancreatic and parotid wet weight and thereby also the protein and amylase contents, and pancreatic DNA content was decreased. There was a significant correlation between the pancreas and parotid glands when comparing these parameters. The concentration of plasma CCK was unaffected by TPN. PBD caused a sevenfold increase in plasma CCK and a threefold increase in the pancreatic weight compared to control rats 28 d after the operation. The protein and DNA contents in the pancreas were found to be increased. The parotid glands increased twofold in weight, but their protein and amylase contents were not affected. There was a significant correlation between the pancreas and parotid glands when comparing weight, and protein and amylase concentrations. Infusion of CCK-8S during 28 d caused a marked increase in pancreatic wet wt and protein and DNA contents. The CCK-A receptor antagonist devazepide induced a reduction in protein and DNA contents in the pancreas. The parotid glands were not affected by either treatment. No effect on the labeling index of serous and ductal cells of the parotid gland was seen at 36 h, 3, 7, and 28 d of infusion with CCK-8S or devazepide.