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孤儿G蛋白偶联受体55在糖尿病性胃轻瘫小鼠发病中的作用

林旭红, 魏丹丹, 王慧超, 王斌, 白春洋, 王亚强, 李国恩, 李荟苹, 任学群^*

河南大学1淮河医院检验科；2第一附属医院肾内科；3淮河医院消化内科；4淮河医院普外科，开封 475000

摘要

文旨在探讨孤儿G蛋白偶联受体55 (GPR55)在糖尿病性胃轻瘫(diabetic gastroparesis, DG)小鼠发病中的作用。采用链脲菌素(streptozotocin, STZ, 65 mg/kg)腹腔注射制备小鼠DG模型。观察造模后小鼠体重及血糖含量变化，同时测定胃电图和酚红排空功能，用放射免疫分析法测定血浆胃动素(motilin, MTL)、胃泌素(gastrin, GAS)、血管活性肠肽(vasoactive intestinal peptide, VIP)、生长抑素(somatostatin, SS)水平，用Real-time PCR和Western blot测定胃组织GPR55表达，用免疫组织化学法观察胃组织GPR55分布，并观察GPR55激动剂溶血磷脂酰肌醇(lysophosphatidylinositol, LPI)对DG的治疗作用。结果显示，STZ组小鼠血糖于STZ注射后第4周末升至(26.6 ± 1.2) mmol/L，体重明显减轻，胃电图慢波振幅下降，胃排空能力明显降低，而腹腔注射LPI可逆转STZ导致的上述变化；STZ小鼠血浆中MTL、GAS明显低于对照组(P < 0.01)，而SS、VIP明显升高(P < 0.01)，LPI可拮抗STZ对四种激素的影响；GPR55存在于正常小鼠胃组织，在DG时其表达明显上调，LPI不影响正常小鼠GPR55表达和分布，但可拮抗STZ对GPR55表达和分布的影响。以上结果提示，GPR55参与调节DG胃运动，可以作为DG治疗的新靶点；GPR55激动剂LPI对STZ导致的DG小鼠有保护作用，该作用机制与GPR55表达的改变、胃肠激素的调整有关。

关键词： G蛋白偶联受体55; 糖尿病性胃轻瘫; 溶血磷脂酰肌醇

分类号：R363.2

[Role of orphan G protein-coupled receptor 55 in diabetic gastroparesis in mice.] [Article in Chinese]

LIN Xu-Hong, WEI Dan-Dan, WANG Hui-Chao, WANG Bin, BAI Chun-Yang, WANG Ya-Qiang, LI Guo-En, LI Hui-Ping, REN Xue-Qun^*

1Department of Clinical Laboratory, Huaihe Hospital Affiliated to Henan University, Kaifeng 475000, China； 2Department of Nephrology, First Affiliated Hospital of Henan University, Kaifeng 475000, China； 3Department of Digestive Medicine, Huaihe Hospital Affiliated to Henan University, Kaifeng 475000, China； 4Department of General Surgery, Huaihe Hospital Affiliated to Henan University, Kaifeng 475000, China

Abstract

The aim of the present study was to explore the role of orphan G protein-coupled receptor 55 (GPR55) in diabetic gastroparesis (DG). Streptozotocin (STZ) was used to mimic the DG model, and the body weight and blood glucose concentration were tested 4 weeks after STZ injection (i.p.). Electrogastrogram and phenolsulfonphthalein test were used for detecting gastric emptying. Motilin (MTL), gastrin (GAS), vasoactive intestinal peptide (VIP), and somatostatin (SS) levels in plasma were determined using radioimmunology. Real-time PCR and Western blot were applied to identify the expression of GPR55 in gastric tissue, and immunohistochemistry was used to detect the distribution. The effect of lysophosphatidylinositol (LPI), an agonist of GPR55, was observed. STZ mice showed increased blood glucose concentration, lower body weight, decreased amplitude of slow wave, and delayed gastric emptying. LPI antagonized these effects of STZ. Compared to the control group, STZ caused significant decreases of MTL and GAS levels (P < 0.01), as well as increases of SS and VIP levels (P < 0.01). The changes of these hormones induced by STZ were counteracted when using LPI. GPR55 located in mice stomach, and it was up-regulated in DG. Although LPI showed no effects on the distribution and expression of GPR55 in normal mice, it could inhibit STZ-induced GPR55 up-regulation. These results suggest GPR55 is involved in the regulation of gastric movement of DG, and may serve as a new target of DG treatment. LPI, an agonist of GPR55, can protect against STZ-induced DG, and the mechanism may involve the change of GPR55 expression and modification of gastrointestinal movement regulating hormones.

Key words: G protein-coupled receptor 55; diabetic gastroparesis; lysophosphatidylinositol

收稿日期：2013-09-17　　录用日期：2013-11-07

通讯作者：任学群　　E-mail: hhyyrxq@126.com

引用本文：

林旭红, 魏丹丹, 王慧超, 王斌, 白春洋, 王亚强, 李国恩, 李荟苹, 任学群. 孤儿G蛋白偶联受体55在糖尿病性胃轻瘫小鼠发病中的作用[J]. 生理学报 2014; 66 (3): 332-340.

LIN Xu-Hong, WEI Dan-Dan, WANG Hui-Chao, WANG Bin, BAI Chun-Yang, WANG Ya-Qiang, LI Guo-En, LI Hui-Ping, REN Xue-Qun. [Role of orphan G protein-coupled receptor 55 in diabetic gastroparesis in mice.] [Article in Chinese]. Acta Physiol Sin 2014; 66 (3): 332-340 (in Chinese with English abstract).