Effect and mechanism of intraperitoneal injection of APETx2 on visceral sensitivity in mice with post-infectious irritable bowel syndrome
ZHANG Jie
YAN Bo
ZHAO Haoyun
CAI Jie
PENG Qidi
ZHANG Dongdong
YUAN Liping
Abstract：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 120 µg/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.
Keywords：irritable bowel syndromeacid-sensing ion channel 3 specific antagonistvisceral sensitivitySTIM1 geneSARAF geneOrai1 gene
Publication Date：2025-02-28
Online Publishing Date：2025-08-15(First online date of this platform, not the publication date of the document)
Pages：5( 11-15 )