酸敏感离子通道3对肠易激综合征大鼠内脏高敏感性的影响及其机制  

Effect and mechanism of acid-sensing ion channel 3 on visceral hypersensitivity in rats with irritable bowel syndrome

作　　者：张立霞 闫波[3] 潘颖 田平平 张卫洁 李欢 袁丽萍[1] Zhang Li-Xia;Yan Bo;Pan Ying;Tian Ping-Ping;Zhang Wei-Jie;Li Huan;Yuan Li-Ping(Department of Pediatrics,the First Affiliated Hospital of Anhui Medical University,Hefei,Anhui 230022,China;Department of Pediatrics,Suzhou Hospital of Anhui Medical University,Suzhou,Anhui 234000,China;Department of Medical Technology,Anhui Medical College,Hefei,Anhui 230026,China)

机构地区：[1]安徽医科大学第一附属医院儿科,安徽合肥230022 [2]安徽医科大学附属宿州医院儿科,安徽宿州234000 [3]安徽医学高等专科学校医学技术系,安徽合肥230026

出　　处：《解放军医学杂志》2023年第10期1162-1166,共5页Medical Journal of Chinese People's Liberation Army

基　　金：安徽高校自然科学研究重大项目(KJ2020ZD67)。

摘　　要：目的探讨酸敏感离子通道3(ASIC3)对肠易激综合征(IBS)大鼠内脏敏感性的影响及可能的信号通路调节机制。方法孕龄鼠产后第2天开始,将分娩的6只幼鼠与母鼠继续在原笼中饲养,作为对照组,其余幼鼠采取母婴分离(NMS)法制作IBS模型。待NMS幼鼠生长至成年(8周龄),通过腹部回撤反射(AWR)评分筛选出16只造模成功的大鼠,将其随机分为NMS组(n=8)与NMS+APETx2组(n=8),NMS+APETx2组每日给予ASIC3特异性阻滞剂APETx2100μg/kg腹腔注射,NMS组及对照组腹腔注射等量生理盐水,持续1周。采用AWR评分评估内脏敏感性,墨汁染色法检测肠道传输速率以评估肠道动力,ELISA法检测结肠组织5-羟色胺(5-HT)水平,免疫组化法检测结肠组织5-HT4受体、ASIC3表达水平。结果与对照组比较,NMS组大鼠在结直肠压力为40、60、80 mmHg时的AWR评分明显增加,肠道传输速率降低,5-HT、ASIC3及5-HT4受体表达水平升高,差异均有统计学意义(P<0.01);而与对照组比较,NMS+APETx2组的AWR评分及肠道传输速率无明显变化(P>0.05),但结肠组织5-HT、ASIC3及5-HT4受体表达水平升高,差异均有统计学意义(P<0.01)。与NMS组比较,NMS+APETx2组大鼠AWR评分降低,肠道传输速率增高,5-HT、ASIC3及5-HT4R受体表达水平降低,差异均有统计学意义(P<0.01或P<0.05)。结论ASIC3参与了IBS大鼠内脏高敏感性的形成,可能与其促进大鼠体内5-HT通路活化有关。Objective To explore the effect and mechanism of acid-sensitive ion channel 3(ASIC3)expression on visceral sensitivity in irritable bowel syndrome(IBS)rats and the possible regulatory mechanisms of signalling pathways.Methods From the 2nd day postpartum,6 neonatal rats and their mother were kept in their original cages as control group;the rest of the neonatal rats were separated from their mother to make IBS models.After the neonatal rats grow into rats,use abdominal withdrawal reflex(AWR)score to screen 16 rats that were successful in IBS modeling,and they were randomly divided into neonatal maternal separation(NMS)group and NMS+APETx2 group,with 8 rats in each group.NMS+APETx2 group was given the ASIC3-specific blocker APETx2100μg/kg intraperitoneally for 1 week while NMS group and control group were intraperitoneally injected with same amount of normal saline.Visceral pain response was measured by abdominal withdraw reflex(AWR)score,the intestinal transmission rate was measured by ink staining,the 5-hydroxytrgptamine(5-HT)level in colonic tissue was measured by enzyme-linked immunosorbent assay(ELISA),and the expression levels of 5-HT4 receptor and ASIC3 in colonic tissue were measured by immunohistochemistry.Results Compared with control group,rats in NMS group showed significantly increased AWR scores at colorectal pressures of 40,60,80 mmHg,decreased intestinal transmission rate,intestinal 5-HT,ASIC3 and 5-HT4 receptor expression increased,all with statistically significant differences(P<0.01).There was no significant difference in AWR score and intestinal propulsion rate in NMS+APETx2 group compared with control group(P>0.05),but the expression levels of 5-HT,ASIC3 and 5-HT4 receptors increased compared with control group with significant difference(P<0.01).Compared with NMS group,the application of ASIC3-specific blocker APETx2 in NMS+APETx2 group resulted in lower AWR scores,enhanced intestinal transmission rate,and the expression levels of 5-HT,ASIC3 and 5-HT4 receptor decreased,and the differences we

关 键 词：肠易激综合征 酸敏感离子通道3 APETx2 5-羟色胺 5-羟色胺4受体 

分 类 号：R725.7[医药卫生—儿科]