胃泌素受体在胃癌中表达的意义

目的研究胃癌组织表达胃泌素受体（ＧＲ）的特征,是临床应用ＧＲ拮抗剂调控胃癌细胞生长的基础。方法应用受体的放射配基结合分析法测定３４例胃癌及癌旁胃粘膜组织ＧＲ含量及亲和力（Ｋｄ）。结果３４例胃癌组织中,１６例胃癌组织ＧＲ阳性,其中２例属低亲和力ＧＲ;１４例属高亲和力ＧＲ,计高含量ＧＲ９例（３９．５４±１４．４３ｆｍｏｌ／ｍｇ蛋白）和低含量ＧＲ５例（６．０３±２．８３ｆｍｏｌ／ｍｇ蛋白）。胃癌组织表达高含量ＧＲ的平均含量较癌旁胃粘膜组织高。胃体癌表达高亲和力ＧＲ的阳性率为７７．８％,胃底贲门癌为５０．０％,而胃窦癌为２１．１％。晚期胃癌表达高亲和力ＧＲ的阳性率为５２．２％,早、中期胃癌为１０．０％。结论４７．１％胃癌组织能表达ＧＲ;高亲和力、高含量ＧＲ在胃体癌、胃底贲门癌中表达的阳性率高;晚期胃癌表达的ＧＲ多属高亲和力。     

胆囊收缩素与糖尿病

胆囊收缩素是一类作用广泛的胃肠激素,近来的研究表明胆囊收缩素及其受体水平的变化或基因突变可能与糖尿病发病有关。通过其受体的介导,胆囊收缩素具有调节中枢摄食,能量平衡,刺激胰岛素分泌,抗炎及通过抑制蛋白酪氨酸碳酸酶1B减轻胰岛素抵抗等功能,具有潜在的糖尿病治疗作用。     

推按运经仪对家兔胆囊壁胆囊收缩素受体基因表达的影响

[目的]观察推按运经仪对家兔胆囊壁胆囊收缩素(CCKA)受体基因表达的影响及其作用机制.[方法]将30只胆囊结石家兔随机分为2组,各15只,对照组不行推按运经仪治疗;实验组空腹时每日行推按运经仪治疗,观察2组胆囊体积和胆囊壁CCK-A受体基因表达的差异.[结果]实验组胆囊体积明显小于对照组,而胆囊平滑肌CCK A受体基因表达明显大于对照组,差异均有统计学意义(P＜0.05).[结论]推按运经仪治疗胆囊结石可增强胆囊壁CCK-A受体基因表达,加强胆囊收缩,可能是其防治胆囊结石的作用机制之一.     

胆囊收缩素受体及胆囊运动与胆囊结石形成相关性研究进展

胆囊结石是消化系统的常见病 ,国内外多年的研究已证实胆囊结石的形成与胆囊运动功能障碍有密切的关系。为了从分子水平更进一步地探讨胆囊结石的成因 ,近年来国内外学者开始了对胆囊收缩素受体的研究。通过一系列的研究发现 ,胆囊收缩素受体的变化影响胆囊的运动功能 ,从而导致胆囊结石的形成。     

胆囊收缩素与消化道运动

胆囊收缩素（CCK）是一种重要的脑肠肽激素，对消化道运动有广泛而重要的调节功能，本综述CCK的分子结构和受体，对消化道运动的调节作用及CCK与消化道动力性疾病的关系。     

胆囊收缩素与消化道运动

胆囊收缩素(CCK)是一种重要的脑肠肽激素,对消化道运动有广泛而重要的调节功能。本文综述CCK的分子结构和受体,对消化道运动的调节作用及CCK与消化道动力性疾病的关系。     

胰腺癌胆囊收缩素受体蛋白表达的研究

目的探讨胆囊收缩素受体在正常胰腺组织、胰腺癌组织、胰腺癌细胞株SW1990中的表达，以明确胆囊收缩素受体与胰腺癌的关系。方法应用免疫组织化学法和免疫细胞化学法分别检测正常胰腺组织、胰腺癌组织、胰腺癌细胞株SW1990中胆囊收缩素受体A、B亚型的表达。结果在正常胰腺组织中缺乏胆囊收缩素受体A、B亚型的表达；在胰腺癌组织、人胰腺癌细胞株SW1990中也不表达胆囊收缩素受体A亚型，但可见胆囊收缩素受体B亚型的表达；胆囊收缩素受体在癌细胞株SW1990中的表达主要位于细胞膜上，细胞质内也可见。结论胆囊收缩素受体B在胰腺癌组织、腺癌细胞株SW1990中表达；胆囊收缩素受体B亚型主要位于细胞膜上；胆囊收缩素受体B亚型在胰腺癌细胞生长中可能发挥重要作用。     

胰腺癌组织中胆囊收缩素B受体的表达

检测20例胰腺癌组织（观察组）和4例正常胰腺组织（对照组）中的胆囊收缩素B（CCKB）受体的表达情况,分析其与临床分期和病理分级之间的关系。结果观察组CCKB受体mRNA阳性17例,对照组均为阴性;观察组CCKB受体蛋白阳性15例,阳性颗粒主要分布在癌细胞的胞膜和胞质中,对照组均为阴性。不同病理学、组织学分级间CCKB受体阳性表达率无统计学差异（P均〉0.05）。表明CCKB受体在肿瘤的发生发展过程中具有一定作用,可用于胰腺癌临床诊断和治疗。     

胰腺癌胆囊收缩素受体蛋白表达的研究

目的探讨胆囊收缩素受体在正常胰腺组织、胰腺癌组织、胰腺癌细胞株SW1990中的表达,以明确胆囊收缩素受体与胰腺癌的关系.方法应用免疫组织化学法和免疫细胞化学法分别检测正常胰腺组织、胰腺癌组织、胰腺癌细胞株SW1990中胆囊收缩素受体A、B亚型的表达.结果在正常胰腺组织中缺乏胆囊收缩素受体A、B亚型的表达;在胰腺癌组织、人胰腺癌细胞株SW1990中也不表达胆囊收缩素受体A亚型,但可见胆囊收缩素受体B亚型的表达;胆囊收缩素受体在癌细胞株SW1990中的表达主要位于细胞膜上,细胞质内也可见.结论胆囊收缩素受体B在胰腺癌组织、腺癌细胞株SW1990中表达;胆囊收缩素受体B亚型主要位于细胞膜上;胆囊收缩素受体B亚型在胰腺癌细胞生长中可能发挥重要作用.     

八肽胆囊收缩素对体外胰岛素β细胞增殖及胰岛素分泌的影响

目的 研究八肽胆囊收缩素（cholecystokinin，CCK-8）对小鼠胰岛β细胞（NIT-1细胞）增殖及胰岛素分泌的影响。方法 体外培养NIT-1细胞，分别加入10^-8～10^10mmol／L浓度CCK-8处理24和48h，MTT法检测NIT-1细胞增殖情况；放免法检测用药后NIT-1细胞胰岛素分泌量。结果 与对照组比较，经不同CCK-8处理24及48h后均可显著提高NIT-1细胞的增殖及胰岛素分泌量，且具有剂量及时间依赖性。10^-8mmol／LCCK-8组与对照组相比，可提高增殖率分别为24h 48％，48h 77％；与对照组比较，10^-8mmol／LCCK-8组可增加胰岛素释放量分别为24h 181％，48h 151％。结论 CCK-8具有显著增强NIT-1胰岛β细胞增殖及胰岛素分泌的作用。     

促胃液素及其受体拮抗剂丙谷胺对人胃癌细胞系生长的影响

目的观察和分析五肽促胃液素ＰＧ及其受体拮抗剂丙谷胺ＰＧＭ对人胃癌细胞系ＭＧＣ生长的影响,为临床应用促胃液素受体拮抗剂协助治疗胃癌提供依据．方法选用５ｍｇ／Ｌ,１０ｍｇ／Ｌ,１５ｍｇ／Ｌ,２０ｍｇ／Ｌ４种浓度的ＰＧ和３０ｍｇ／Ｌ的ＰＧＭ分别作用于体外培养的浓度为２５×１０８／Ｌ的ＭＧＣ,分别培养２４,４８,７２ｈ,于酶标仪上选用波长５４０ｎｍ测定吸光值Ａ,并对数据进行比较分析．结果４种浓度的ＰＧ作用于ＭＧＣ,ＭＧＣ连续３ｄ的生长状态与对照组无明显差异,而ＭＧＣ在ＰＧＭ作用下,其连续３ｄ的平均Ａ值分别为００２９,００４６和００８４,而未被ＰＧＭ作用的ＭＧＣ的平均Ａ值分别是０１０１,０１１５和０１８２,ＭＧＣ在ＰＧＭ作用下生长明显低于对照组（Ｐ＜００５）．结论外源性的ＰＧ对ＭＧＣ无营养促进作用,而ＰＧＭ能抑制ＭＧＣ的生长     

CacyBP/SIP nuclear translocation induced by gastrin promotes gastric cancer cell proliferation

AIM:To investigate the role of nuclear translocation of calcyclin binding protein,also called Siah-1 interacting protein(CacyBP/SIP),in gastric carcinogenesis.METHODS:The expression of CacyBP/SIP protein in gastric cancer cell lines was detected by Western blot.Immunofluorescence experiments were performed on gastric cancer cell lines that had been either unstimulated or stimulated with gastrin.To confirm the immunofluorescence findings,the relative abundance of CacyBP/SIP in nuclear and cytoplasmic compartments was assessed by Western blot.The effect of nuclear translocation of CacyBP/SIP on cell proliferation was examined using MTT assay.The colony formation assay was used to measure clonogenic cell survival.The effect of CacyBP/SIP nuclear translocation on cell cycle progression was investigated.Two CacyBP/SIPspecific siRNA vectors were designed and constructed to inhibit CacyBP/SIP expression in order to reduce the nuclear translocation of CacyBP/SIP,and the expression of CacyBP/SIP in stably transfected cells was determined by Western blot.The effect of inhibiting CacyBP/SIP nuclear translocation on cell proliferation was then assessed.RESULTS:CacyBP/SIP protein was present in most of gastric cancer cell lines.In unstimulated cells,CacyBP/SIP was distributed throughout the cytoplasm;while in stimulated cells,CacyBP/SIP was found mainly in the perinuclear region.CacyBP/SIP nuclear translocation generated a growth-stimulatory effect on cells.The number of colonies in the CacyBP/SIP nuclear translocation group was significantly higher than that in the control group.The percentage of stimulated cells in G1phase was significantly lower than that of control cells(69.70%±0.46%and 65.80%±0.60%,control cells and gastrin-treated SGC7901 cells,P=0.008;72.99%±0.46%and 69.36%±0.51%,control cells and gastrin-treated MKN45 cells,P=0.022).CacyBP/SIPsi1effectively down-regulated the expression of CacyBP/SIP,and cells stably transfected by CacyBP/SIPsi1 were then chosen for further cellular assays.In CacyBP/SIPsi1 stably transfected cells,CacyBP/SIP was shown to be distributed throughout the cytoplasm,irregardless of whether they were stimulated or not.After CacyBP/SIP nuclear translocation was reduced,there had no major effect on cell proliferation,as shown by MTT assay.There had no enhanced anchoragedependent growth upon stimulation,as indicated by colony formation in flat plates.No changes appeared in the percentage of cells in G0-G1 phase in either cell line(71.09%±0.16%and 70.86%±0.25%,control cells and gastrin-treated SGC7901-CacyBP/SIPsi1 cells,P=0.101;74.17%±1.04%and 73.07%±1.00%,control cells and gastrin-treated MKN45-CacyBP/SIPsi1cells,P=0.225).CONCLUSION:CacyBP/SIP nuclear translocation promotes the proliferation and cell cycle progression of gastric cancer cells.     

二甲双胍对AGS胃癌细胞生长侵袭的抑制作用

目的:研究应用安全性较好的二甲双胍对胃癌细胞的抑制作用,初步探讨可能机制.方法:以二甲双胍联合或不联合5-氟尿嘧啶干预AGS细胞作为实验组,无药物组作对照.干预24、48、72 h应用MTT检测细胞增殖,干预48 h流式细胞术检测凋亡、线粒体膜电位,72 h通过细胞划痕实验反映迁移能力改变.药物作用24 h抽提细胞RNA以RT-PCR检测相关基因转录改变.结果:AGS细胞相对活力明显降低(24、48、72h:F=99.32,127.30,235.72,均P<0.01),并具有浓度-时间依赖性,联合应用5-氟尿嘧啶显示协同作用(24h:t=2.97,P<0.05;48、72h:t=4.61,6.02,均P<0.01).线粒体膜电位下降(t=12.43,P<0.01),凋亡增加(t=8.32,P<0.01),平均迁移速率明显减慢(12、24、48 h:t=9.13,13.77,14.21,均P<0.01),cyclin D1、Bcl-2、MMP-2、MMP-9 mRNA均减少,Bax增加.结论:二甲双胍能够抑制AGS胃癌细胞增殖、迁移,促进凋亡,与5-氟尿嘧啶联合应用具有协同抑制作用.     

Effect of gastrin on gastric mucosal cell proliferation in man.

The effect of short-term infusion of a large dose of pentagastrin and a small dose of synthetic human gastrin I (SHG) on the rate of cell proliferation in gastric mucosa was studied in normal human subjects. Moreover, the kinetic parameters were compared with the serum gastrin concentrations in fasting patients. Endoscopic biopsies were labelled in vitro with 3H-thymidine and autoradiographs were prepared. The percentage of DNA-synthesising cells in the progenitor cell region was estimated. In healthy volunteers infusion of a large dose of pentagastrin (10 mug/kg per hour) was followed by a marked increase in the labelling index in fundic mucosa. The antral mucosa was not responsive to this effect. In the same subjects, infusion of a low dose of SHG (8 ng/kg per min) did not affect the rate of cell proliferation, either in fundic or in antral mucosa. In 46 patients with different gastric diseases no correlation between the serum gastrin concentrations and the labelling indices was found. The results suggest that human fundic mucosa is responsive to a trophic action of pentagastrin. If it exists, however, a physiological action of gastrin as a trophic hormone for human gastric mucosa must be considerably more complex than previously believed.     

曲古菌素A对人胃癌细胞增殖和细胞周期的作用

目的 观察曲古菌素A(TSA)对人胃癌细胞株SGC-7901细胞增殖及细胞周期的影响,探讨其可能的机制.方法 TSA干预人胃癌SGC-7901细胞24 h后.采用四甲基偶氮唑盐法检测其对细胞增殖的影响,流式细胞技术检测细胞周期,实时PCR检测细胞周期素D1和p21 mRNA的表达情况.结果 经TSA干预24 h后,人胃癌SGC-7901细胞增殖受抑制,TSA 0.1、0.5和2.0μmol/L组抑制率分别为3.52%±6.11%、13.29%±4.13%和14.24%±2.80%;同时TSA 0.5μmol/L组(71.26%±0.51%)和TSA 2.0μmol/L组(71.03%±0.12%)的G0/Gl期细胞比例明显高于对照组(51.12%±1.17%);TSA 0.5μmol/L组(13.55%±0.44%)和TSA 2.0 μmol/L组(10.63%±0.63%)的S期细胞比例明显低于对照组(34.60%±0.60%).出现G0/G1细胞周期阻滞.TSA干预后细胞周期相关基因细胞周期素D1 mRNA表达下调和p21 mRNA表达上调.结论 TSA通过调控细胞周期相关基因细胞周期素D1和p21的表达,抑制人胃癌SGC-7901细胞的增殖,引起G0/G1期细胞周期阻滞,最终影响肿瘤细胞的生长.     

胃泌素受体拮抗剂丙谷胺对原代培养大肠癌细胞作用的研究

目的：在体外观察胃泌素受体持抗剂丙谷胺（PGL）对原代培养大肠癌活细胞数（吸光度，A值）和DNA合成（脉冲数，CPM值）的影响，为大肠癌病人临床应用胃泌素受体拮抗剂治疗提供实验依据。方法：对25例大肠癌根治术病人的新鲜标本进行细胞分离和原代培养，采用MTT比色分析法检测活细胞数；3H－TdR掺入法测定DNA合成．结果：PGL组高、中和低分化腺癌活细胞数和DNA合成与对照组比差异均无显著性（P均>0.05),5肽胃泌素（PG）组活细胞数和DNA合成均显著高于对照组（P均＜0．01），PGL＋PG组活细胞数和DNA合成均显著低于PG组（P均＜0．01），而与对照组比差异无显著性（P均＞0．05）。结论：丙谷胺对原代培养大肠癌细胞的增殖无明显影响，但可抑制胃泌素对大肠癌细胞的促增殖作用。     

吴茱萸碱对人胃癌SGC7901细胞增殖、侵袭的影响及机制探讨

目的观察吴茱萸碱对胃癌细胞增殖、侵袭的影响,并探讨其机制。方法采用不同浓度的吴茱萸碱处理人胃癌细胞SGC7901,用软琼脂集落培养试验检测癌细胞增殖情况,Boyden小室检测癌细胞侵袭能力;分别采用荧光实时定量RT-PCR法和Western blot法检测癌细胞中的中期因子（MK）mRNA及其蛋白。结果 SGC7901经吴茱萸碱处理后,恶性增殖和穿膜细胞数均明显下降,且呈剂量依赖性（P均〈0.05）;吴茱萸碱处理后,SGC7901的MK mRNA及蛋白表达均明显下调,且呈时间、浓度依赖性（P均〈0.01）。结论吴茱萸碱可明显抑制胃癌细胞的增殖及侵袭能力,其机制可能与下调MK基因表达有关。