盐酸洛哌丁胺促进大鼠结肠黏膜下神经丛小胶质细胞M2极化  

Loperamide hydrochloride promotes M2 polarization of microglia in submucosal plexus of colon in rats

作　　者：罗慧娟 赵玉琼 任博 任晓洁 贾冰涵 白晓燕 李军平[1] LUO Huijuan;ZHAO Yuqiong;REN Bo;REN Xiaojie;JIA Binghan;BAI Xiaoyan;LI Junping(Department of Human Anatomy,Histology and Embryology,School of Basic medicine,Ningxia Medical University,Yinchuan 750004,China)

机构地区：[1]宁夏医科大学基础医学院人体解剖与组织胚胎学系,银川750004

出　　处：《神经解剖学杂志》2023年第5期509-516,共8页Chinese Journal of Neuroanatomy

基　　金：国家自然科学基金(31860275);宁夏自然科学基金(2022AAC02032)。

摘　　要：目的:利用阿片类药物诱发结肠运动功能障碍(OICMD)大鼠模型,探究肠内小胶质细胞在OICMD大鼠结肠黏膜下神经丛的分布特点及优势表型。方法:将大鼠随机分为正常对照组(NCG)、生理盐水组(NSG)和阿片类药物诱发结肠运动功能障碍组(OICMD)。腹腔注射盐酸洛哌丁胺溶液(5 mg/kg)制备OICMD大鼠模型;通过测量造模过程中3组大鼠体重变化以及对比3组大鼠在造模结束12 h后肠道推进速度进行模型评价;运用免疫荧光组织化学双重标记技术检测离子钙接头蛋白分子1(Iba-1)和跨膜蛋白119(TMEM119)与μ阿片受体(MOR)、精氨酸酶1(Arg1)和CD86在远段结肠黏膜下神经丛细胞中的分布特点;采用Western Blot方法检测Iba-1、Arg1、CD86、白细胞介素-4(IL-4)、白细胞介素-1β(IL-1β)等在远段结肠黏膜下层的表达。结果:OICMD大鼠在造模第2 d时,体重明显下降,随着造模时间延长,体重又缓慢增加,约3 g/d;造模结束12 h后,OICMD大鼠肠道推进速度明显降低(P<0.05);免疫荧光组织化学双重标记显示,在大鼠远段结肠黏膜下神经丛内可见TMEM119、MOR、Arg1和CD86等阳性细胞分布,并且均与Iba-1有共存;Western Blot结果显示,OICMD大鼠远段结肠黏膜下层内Iba-1和MOR及M2型表型相关因子Arg1、IL-4表达明显增加(P<0.05),而M1型表型相关因子CD86、IL-1β的表达明显降低(P<0.05)。结论:在大鼠远段结肠黏膜下神经丛内有肠内小胶质细胞分布;OICMD大鼠结肠黏膜下神经丛中肠内小胶质细胞被激活,主要表现为M2型。Objective:Using the opioid-induced colonic motility disorder(OICMD)rat model explore the distribution characteristics and dominant phenotypes of intestinal microglia in the submucosal plexus of the colon.Methods:Experimental rats were randomly divided into normal control group(NCG),normal saline group(NSG),and opioid-induced colonic motility disorder group(OICMD).Rats in the model group were prepared by intraperitoneal injection of loperamide hydrochloride solution(5 mg/kg).The model evaluation was carried out by measuring the weight changes of the three groups of rats during the modeling process and comparing the intestinal propulsion velocity of the three groups of rats 12 h after the end of the modeling.The distribution characteristics of ionized calcium-binding adaptor molecule-1(Iba-1)and transmembrane protein 119(TMEM119),μopioid receptor(MOR),arginase 1(Arg1),and CD86 in distal colonic submucosal plexus cells were detected by immunofluorescence histochemical double labeling technology.Western Blot was used to observe the expression changes of Iba-1,Arg1,CD86,interleukin-4(IL-4),and interleukin-1β(IL-1β)in colonic submucosa.Results:The weight of OICMD rats decreased significantly on the second day of molding,and with the extension of molding,the weight slowly increased,about 3 g/d.After 12 h after the completion of molding,the intestinal propulsion velocity of OICMD rats was significantly reduced(P<0.05).Immunofluorescence histochemical double labeling showed that the distribution of positive cells such as TMEM119,MOR,Arg1,and CD86 in the submucosal plexus of the distant colon of rats was visible,and all coexisted with Iba-1.The Western Blot results showed that the expression of Iba-1,MOR,and M2 phenotypic correspondents Arg1 and IL-4 in the distal submucosa of OICMD rats was significantly increased(P<0.05),while the expression of M1-type phenotypic correspondents CD86 and IL-1βwas significantly reduced(P<0.05).Conclusion:Distribution of intestinal microglia in the submucosal plexus of the distant colon

关 键 词：阿片类诱发结肠运动功能障碍 黏膜下神经丛 Μ阿片受体 肠内小胶质细胞 大鼠 

分 类 号：R965[医药卫生—药理学]