针灸通过阻断BDNF/TrkB信号通路改善肠易激综合征大鼠的肠道屏障功能和内脏疼痛  

Acupuncture improves intestinal barrier function and visceral pain in rats with irritable bowel syndrome by blocking BDNF/TrkB signaling pathway

作　　者：杨敏 辛欢 邹燃 王琼 李悦 YANG Min;XIN Huan;ZOU Ran;WANG Qiong;LI Yue(Department of Acupuncture and Moxibustion,Wuhan Integrated Traditional Chinese and Western Medicine Hospital(Wuhan First Hospital),Wuhan 430030,China)

机构地区：[1]武汉市中西医结合医院(武汉市第一医院)针灸科,武汉430030

出　　处：《中国免疫学杂志》2024年第6期1234-1239,共6页Chinese Journal of Immunology

基　　金：湖北省卫生健康委员会联合基金项目(WJ2019H418)。

摘　　要：目的:探究针灸是否通过调节脑源性神经营养因子(BDNF)及其下游酪氨酸激酶受体B(TrkB)对肠易激综合征(IBS)大鼠的肠道屏障和内脏疼痛产生影响,探究BDNF/TrkB信号通路作为针灸治疗新靶点的可能性。方法:将60只SD大鼠随机分为健康组、IBS组、针灸组、阳性对照组、针灸+TrkB激活组,每组12只。建立IBS大鼠模型,腹部撤回反射(AWR)检测各组大鼠内脏疼痛;检测各组大鼠结肠TNF-α、IL-1β水平;免疫组化检测结肠黏膜胞质紧密黏连蛋白1(ZO-1)、闭合蛋白(occludin)表达水平;荧光定量PCR及Western blot检测各组大鼠结肠BDNF、TrkB mRNA及蛋白表达水平。结果:与健康组相比,IBS组大鼠结肠黏膜出现破损,ZO-1、occludin表达显著降低,大鼠AWR评分、粪便含水量、TNF-α、IL-1β含量、结肠BDNF、TrkB mRNA及BDNF蛋白表达量、TrkB磷酸化程度显著升高(P<0.05);与IBS组相比,针灸组、阳性对照组大鼠结肠黏膜逐渐恢复,ZO-1、occludin表达显著升高,大鼠AWR评分、粪便含水量、TNF-α、IL-1β含量、结肠BDNF、TrkB mRNA及BDNF蛋白表达量、TrkB磷酸化程度显著降低(P<0.05);与针灸组相比,针灸+TrkB激活组大鼠结肠黏膜仍有病变,ZO-1、occludin表达显著降低,大鼠AWR评分、粪便含水量、TNF-α、IL-1β含量、结肠BDNF、TrkB mRNA及BDNF蛋白表达量、TrkB磷酸化程度显著升高(P<0.05)。结论:针灸可通过调控BDNF/TrkB通路,抑制相关蛋白表达,改善肠道屏障功能,减轻内脏疼痛及炎症反应,缓解IBS。Objective:To explore whether acupuncture can affect intestinal barrier and visceral pain of rats with irritable bowel syndrome(IBS)by regulating brain-derived neurotrophic factor(BDNF)and its downstream tyrosine kinase receptor B(TrkB),and to explore the possibility of BDNF/TrkB signaling pathway as a new target for acupuncture treatment.Methods:Sixty SD rats were ran-domly grouped into healthy group,IBS group,acupuncture group,positive control group and acupuncture+TrkB activation group,with 12 rats in each group.An IBS rat model was established,abdominal withdrawal reflex(AWR)was used to detect visceral pain of rats in each group;levels of TNF-αand IL-1βin colon of rats in each group were measured;expression levels of colonic mucosal cyto-plasmic Claudin 1(ZO-1)and occludin were measured with immunohistochemistry;expression levels of BDNF and TrkB mRNA and protein in colon of rats in each group were measured with fluorescence quantitative PCR and Western blot.Results:Compared with healthy group,colonic mucosa of rats in IBS group was damaged,expressions of ZO-1 and occludin were significantly reduced,AWR score,fecal water content,TNF-αand IL-1βcontents,colonic BDNF,TrkB mRNA and BDNF protein expressions,and TrkB phos-phorylation were significantly increased(P<0.05);compared with IBS group,colon mucosa of acupuncture group and positive control group gradually recovered,expressions of ZO-1 and occludin were significantly increased,AWR score,fecal water content,TNF-αand IL-1βcontents,colonic BDNF,TrkB mRNA and BDNF protein expressions,and TrkB phosphorylation were significantly re-duced(P<0.05);compared with acupuncture group,colonic mucosa of rats in acupuncture+TrkB activation group still had lesions,expressions of ZO-1 and occludin were significantly reduced,AWR score,fecal water content,TNF-αand IL-1βcontents,colonic BDNF,TrkB mRNA and BDNF protein expressions,and TrkB phosphorylation were significantly increased(P<0.05).Conclusion:Acupuncture can regulate BDNF/TrkB pathway,inhibit expression of relate

关 键 词：脑源性神经营养因子 酪氨酸激酶受体B 针灸 肠易激综合征 肠道屏障 内脏疼痛 

分 类 号：R574[医药卫生—消化系统]