基础医学与临床2026，Vol.46Issue(6)：765-771,7.DOI:10.16352/j.issn.1001-6325.2026.06.0765
特异性敲除小鼠肠神经系统多巴胺D2受体促进肠道转运
Specific knockout of dopamine D2 receptor in the enteric nervous system promotes intestinal transit in mice
摘要
Abstract
Objective To establish a mouse model with specific knockout of dopamine D2 receptor(D2R)in the enteric nervous system(ENS)and elucidate its mechanism in promoting intestinal motility.Methods The Cre-LoxP system was employed to generate ENS-specific D2R knockout mice(D2RNmu-CKO)and control mice(D2Rflox/flox).Expression levels of D2R and choline acetyltransferase(ChAT)were detected using immunofluores-cence staining,DAB staining,RT-qPCR,and Western blot.Acetylcholine(ACh)content was measured by ELISA.Intestinal transit was assessed in vivo using X-ray imaging in live small animals.Results Immunofluo-rescence staining confirmed the co-localization of D2R with the neuronal marker PGP 9.5 as well as the cholin-ergic neuronal marker ChAT in the duodenal myenteric plexus(MP)of wild-type mice,indicating that D2R is expressed in cholinergic neurons of the duodenal ENS.Genotyping confirmed successful establishment of D2RNmu-CKO mice(genotypes:Nmu-Cre+/+D2R-flox+/+or Nmu-Cre+/-D2R-flox+/+)and control D2Rflox/flox mice(genotype:Nmu-Cre-/-D2R-flox+/+).Compared with control mice,D2RNmu-CKO mice exhibited significantly re-duced mRNA(n=6,P＜0.001)and protein(n=8,P＜0.01)expression of D2R in the duodenal muscle layer,while mRNA(n=6,P＜0.001)and protein(n=6,P＜0.05)expression of ChAT were markedly in-creased.The content of ACh was also significantly elevated(n=8,P＜0.01).DAB staining further revealed a significant increase in the number of ChAT-positive neurons in the duodenal MP of D2RNmu-CKO mice(n=6,P＜0.01).Intestinal transit assays demonstrated accelerated intestinal transit and significantly shortened whole-gut transit time in D2RNmu-CKO mice(n=5,P＜0.05).Conclusions This study successfully established an ENS-specific D2R knockout mouse model and revealed that loss of ENS D2R promotes intestinal transit by enhancing ACh release.These findings provide a theoretical basis for novel strategies targeting ENS D2R to treat gastrointestinal motility disorders such as functional dyspepsia and slow-transit constipation.关键词
肠神经系统/多巴胺D2受体/乙酰胆碱/肠道转运Key words
enteric nervous system/dopamine D2 receptor/acetylcholine/intestinal transit分类
医药卫生引用本文复制引用
汪国庆,朱愔喆,王益嘉,冯小燕..特异性敲除小鼠肠神经系统多巴胺D2受体促进肠道转运[J].基础医学与临床,2026,46(6):765-771,7.基金项目
北京市自然科学基金(7222010) （7222010）
国家自然科学基金(32071126) （32071126）
