APETx2对感染后肠易激综合征小鼠内脏敏感性的作用及机制  

Effects and mechanisms of APETx2 on visceral sensitivity in mice with post-infectious irritable bowel syndrome

作　　者：肖红云 李欢 闫波[2] 潘颖 田平平 袁丽萍 Xiao Hongyun;Li Huan;Yan Bo;Pan Ying;Tian Pingping;Yuan Liping(Dept of Pediatrics,Fuyang Hospital of Anhui Medical University,Fuyang 236112;Dept of Medical Technology,Anhui Medical College,Hefei 230601;Dept of Pediatrics,The First Affiliated Hospital of Anhui Medical University,Hefei 230022)

机构地区：[1]安徽医科大学附属阜阳医院儿科,阜阳236112 [2]安徽医学高等专科学校医学技术系,合肥230601 [3]安徽医科大学第一附属医院儿科,合肥230022

出　　处：《安徽医科大学学报》2023年第6期953-958,共6页Acta Universitatis Medicinalis Anhui

基　　金：安徽省高校科学研究项目(编号:KJ2020ZD67)。

摘　　要：目的探讨酸敏感离子通道3特异性拮抗剂(APETx2)对感染后肠易激综合征(PI-IBS)小鼠内脏敏感性的调控作用及其机制。方法采用旋毛虫感染NIH小鼠建立PI-IBS模型。通过测量首次排黑便的时间和6 h内收集的粪便颗粒数评估胃肠道运输功能;腹壁回撤反射(AWR)评分评估小鼠内脏敏感性;免疫组织化学法检测结肠组织中降钙素基因相关肽(CGRP)蛋白表达;通过实时定量PCR(qRT-PCR)法检测结肠组织中脑源性神经营养因子(BDNF)、CGRP mRNA表达。蛋白质印迹法(Western blot)检测脑组织中酸敏感离子通道3(ASIC3)、CGRP、瞬时受体电位香草素1(TRPV1)蛋白表达。结果与对照组比较,PI-IBS组首次排黑便时间显著降低,6 h内的粪便颗粒数,AWR评分均显著升高,结肠组织中CGRP蛋白表达显著升高,BDNF、CGRP mRNA显著升高,脑组织中CGRP、ASIC3、TRPV1的蛋白表达显著升高;与PI-IBS组比较,APETx2组首次排黑便时间显著延长,6 h内的粪便颗粒数,AWR评分均显著降低,结肠组织中CGRP蛋白表达显著降低,BDNF、CGRP mRNA表达显著降低,脑组织中CGRP、ASIC3、TRPV1的蛋白表达显著降低,差异均有统计学意义(P<0.05)。结论APETx2可通过下调BDNF、CGRP、ASIC3、TRPV1的表达,减轻PI-IBS小鼠的内脏敏感性并调节胃肠道运动。APETx2可能为治疗IBS提供一个新的治疗选择。Objective To investigate the regulatory effect and mechanism of specific antagonist of acid-sensitive ion channel 3(APETx2)on visceral sensitivity in mice with post-infectious irritable bowel syndrome(PI-IBS).Methods The PI-IBS model was established by National Institutes of Health(NIH)mice infected with Trichinella spiralis.Gastrointestinal transport function was assessed by measuring the time to first black stool and the number of fecal pellets collected for 6 hours;abdominal wall withdrawal reflex(AWR)was used to assess visceral sensitivity;the expression of calcitonin gene-related peptide(CGRP)in the colon tissue was detected by immunohistochemistry;the expression of brain-derived neurotrophic factor(BDNF)and CGRP mRNA in the colon tissues was detected by quantitative real time polymerase chain reaction(qRT-PCR).The expression levels of acid sensing ion channel 3(ASIC3),CGRP,and transient receptor potential vanilloid 1(TRPV1)protein in brain tissue were detected by Western blot analysis.Results Compared with the control group,the PI-IBS group significantly reduced the time of first black stool,the number of fecal particles and AWR score within 6 hours significantly increased,the protein expression of CGRP in colon tissue,BDNF and CGRP mRNA significantly increased,and the protein expression of CGRP,ASIC3 and TRPV1 in brain tissue significantly increased.Compared with the control group,the PI-IBS group significantly reduced the time to first black stool,the number of fecal particles and AWR score within 6 hours significantly increased,the expression of CGRP protein in colon tissue,the expression of BDNF and CGRP mRNA significantly increased,and the protein expression of CGRP,ASIC3 and TRPV1 in brain tissue significantly increased;compared with the PI-IBS group,the first time of black stool clearance in the APETx2 group was significantly prolonged,the number of fecal particles and AWR score within 6 hours were significantly reduced,the expression of CGRP protein in colon tissue,the expression of BDNF and CGRP mR

关 键 词：感染后肠易激综合征 APETx2 酸敏感离子通道3 降钙素基因相关肽 脑源性神经营养因子 瞬时受体电位香草素1 

分 类 号：R574.4[医药卫生—消化系统]