艾灸对腹泻型肠易激综合征模型大鼠海马与结肠组织中IKKβ/IKBα/NF-κB通路的影响

目的观察艾灸对腹泻型肠易激综合征(diarrhea predominant irritable bowel syndrome,IBS-D)模型大鼠海马与结肠组织中核因子κB抑制蛋白(inhibitor of nuclear factor kappa B,IκB)激酶β(IκB kinase beta,IKKβ)、核因子κB抑制蛋白α(NF-kappa-B inhibitor alpha,IKBα)、核因子κB(nuclear factor kappa B,NF-κB)(P65)相对表达水平的影响,探讨艾灸治疗IBS-D的机制。方法将24只健康雄性SD大鼠随机分为空白组、模型组和艾灸组,每组8只。采用慢性束缚联合番泻叶灌胃方法建立IBS-D大鼠模型。艾灸组予以艾灸"天枢""上巨虚",每日30min,每日1次,共治疗7d。治疗后,观察大鼠稀便率和直肠扩张所引起腹部回缩反射(abdominal withdrawal reflex,AWR)的最小容量阈值;蛋白质印迹法检测海马和结肠组织中IKKβ、IKBα、NF-κB(P65)蛋白表达水平。结果与空白组比较,模型组AWR的最小容量阈值明显下降(P<0.05),稀便率明显升高(P<0.05);海马和结肠组织中IKKβ、IKBα、NF-κB(P65)蛋白表达水平明显增加(P<0.05)。与模型组比较,艾灸组AWR的最小容量阈值明显升高(P<0.05),稀便率明显下降(P<0.05);海马和结肠组织中IKKβ、IKBα、NF-κB(P65)蛋白表达水平显著降低(P<0.05)。结论艾灸"天枢""上巨虚"改善IBS-D大鼠腹泻症状和内脏高敏感性可能与艾灸抑制海马与结肠组织IKKβ/IKBα/NF-κB信号通路有关,且其作用机制可能是通过脑-肠轴途径实现的。

Effect of Moxibustion on the IKKβ/IKBα/NF-κB Pathway in Hippocampal and Colonic Tissue in a Rat Model of Diarrhea-predominant Irritable Bowel Syndrome

Objective To investigate the effect of moxibustion on the relative expression levels of inhibitor of nuclear factor kappa B(IκB)kinase beta(IKKβ),nuclear factor-kappa-B-inhibitor alpha(IKBα),and nuclear factor kappa B(NF-κB)in hippocampal and colonic tissue in a rat model of diarrhea-predominant irritable bowel syndrome(IBS-D),as well as the mechanism of moxibustion in the treatment of IBS-D.Methods A total of 24 healthy male Sprague-Dawley rats were randomly divided into blank group,model group,and moxibustion group,with 8 rats in each group.A rat model of IBS-D was established by chronic restraint combined with senna by gavage.The rats in the moxibustion group were treated with moxibustion at Tianshu and Shangjuxu for 30 min,once a day for 7 days.After treatment,the rats were observed in terms of the rate of loose stool and the minimum volume threshold of abdominal withdrawal reflex(AWR)caused by rectal distension,and Western blot was used to measure the protein expression of IKKβ,IKBα,and NF-κB(P65)in the hippocampal and colonic tissue.Results Comparedwith the blank group,the model group had a significant reduction in the minimum volume threshold of AWR(P<0.05),a significant increase in the rate of loose stool(P<0.05),and significant increases in the protein expression of IKKβ,IKBα,and NF-κB(P65)in the hippocampal and colonic tissue(P<0.05).Compared with the model group,the moxibustion group had a significant increase in the minimum volume threshold of AWR(P<0.05),a significant reduction in the rate of loose stool(P<0.05),and significant reductions in the protein expression of IKKβ,IKBα,and NF-κB(P65)in the hippocampal and colonic tissue(P<0.05).Conclusion Moxibustion at Tianshu and Shangjuxu can improve the symptoms of diarrhea and visceral hypersensitivity in rats with IBS-D,possibly by inhibiting the IKKβ/IKBα/NF-κB signaling pathway in hippocampal and colonic tissue,which may be achieved via the brain-gut axis.