APETx2腹腔注射对感染后肠易激综合征小鼠内脏敏感性的影响及其机制  

Effect and mechanism of intraperitoneal injection of APETx2 on visceral sensitivity in mice with post-infectious irritable bowel syndrome

作　　者：张洁[1] 闫波[2] 赵昊赟 蔡洁[1] 彭启迪 张冬冬 袁丽萍[1] ZHANG Jie;YAN Bo;ZHAO Haoyun;CAI Jie;PENG Qidi;ZHANG Dongdong;YUAN Liping(Department of Pediatrics,The First Affiliated Hospital of Anhui Medical University,Hefei 230022,China;不详)

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]安徽医学高等专科学校医学技术学院,安徽合肥230601

出　　处：《山东医药》2025年第2期11-15,共5页Shandong Medical Journal

基　　金：安徽省高校自然科学基金重大项目(KJ2020ZD67)。

摘　　要：目的观察酸敏感离子通道3特异性拮抗剂APETx2对感染后肠易激综合征(PI-IBS)小鼠内脏敏感性的影响,并探讨其机制。方法健康雄性NIH小鼠18只,随机分为对照组、模型组、实验组,每组6只。实验组和模型组采用旋毛虫感染NIH小鼠建立PI-IBS模型,对照组不予造模;造模成功后,实验组给予120µg/kg的APETx2腹腔注射,模型组和对照组给予等量0.9%氯化钠溶液腹腔注射,每天1次、共7 d。采用腹壁撤退反射(AWR)评分评估小鼠内脏敏感性;采用免疫组化法检测小鼠小肠组织中的酪氨酸激酶受体(c-Kit)蛋白;取小鼠小肠组织,分离Cajal间质细胞(ICC),采用实时定量PCR法检测ICC中的基质相互作用分子1(STIM1)、钙库操纵性Ca2+内流相关调节因子(SARAF)、钙释放-激活钙通道蛋白1(Orai1)、c-Kit mRNA。结果与对照组相比,模型组AWR评分升高,小肠组织中c-Kit蛋白表达增加,ICC中SARAF、Orai1、c-Kit mRNA表达增高(P均<0.05);与模型组相比,实验组AWR评分降低,小肠组织中c-Kit蛋白表达降低,ICC中SARAF、Orai1 mRNA表达降低(P均<0.05)。结论APETx2腹腔注射可改善PI-IBS小鼠的内脏敏感性,其机制可能与调控ICC中STIM1、SARAF、Orai1基因表达有关。Objective To observe the effect of acid-sensing ion channel 3(ASIC3)specific antagonist(APETx2)on visceral sensitivity in post-infectious irritable bowel syndrome(PI-IBS)mice and to explore its mechanism.Methods Eigh teen healthy male NIH mice were randomly divided into the control group,model group,and experimental group,with six mice in each group.In the model group and the experimental group,we established the PI-IBS models by infecting NIH mice with Trichinella spiralis,while mice in the control group were not modeled.After successful modeling,mice in the experimental group were given intraperitoneal injection of 120µg/kg APETx2,and mice in the model group and the con trol group were given equal volume of 0.9%sodium chloride solution intraperitoneally,once a day,for 7 days.The abdom inal withdrawal reflex(AWR)score was used to assess the visceral sensitivity of the mice.Immunohistochemistry was used to detect the protein expression of tyrosine kinase receptor(c-Kit)in the small intestine tissues.The small intestine tissue was taken to isolate interstitial cells of Cajal(ICC),and real-time quantitative PCR was used to detect the mRNA expres sion levels of stromal interaction molecule 1(STIM1),store-operated calcium entry-associated regulatory factor(SARAF),calcium release-activated calcium channel protein 1(Orai1),and c-Kit in ICC.Results Compared with the control group,the AWR score of the model group increased,the protein expression of c-Kit in the small intestine tissues increased,and the mRNA expression levels of SARAF,Orai1,and c-Kit in ICC increased(all P<0.05).Compared with the model group,the AWR score of the experimental group decreased,the protein expression of c-Kit in the small intestine tissues decreased,and the mRNA expression levels of SARAF and Orai1 in ICC decreased(all P<0.05).Conclusion Intraperi toneal injection of APETx2 can improve the visceral sensitivity of PI-IBS mice,and its mechanism may be related to the regulation of the gene expression of STIM1,SARAF,and Orai1 in ICC.

关 键 词：肠易激综合征 酸敏感离子通道3特异性拮抗剂 内脏敏感性 STIM1基因 SARAF基因 Orai1基因 

分 类 号：R574.4[医药卫生—消化系统]