腸易激综合征模型内脏敏感性的脑-肠轴机制研究

目的观察肠易激综合征(IBS)不同亚型大鼠模型脑-肠神经系统c-fos表达变化,探索IBS内脏敏感性的机制。方法采用冰醋酸加束缚应激的方法建立腹泻型肠易激综合征(IBS-D)动物模型,冰水灌胃法建立便秘型肠易激综合征(IBS-C)动物模型。所有大鼠给予直肠内球囊扩张,检测球囊扩张引起腹部收缩反射的最小容量阈值及球囊不同容量扩张时腹部收缩反射的次数;用免疫组化方法检测各组大鼠海马、下丘脑、空肠、回肠、近端结肠、远端结肠组织中c-fos阳性细胞并进行分析。结果 IBS-D组球囊扩张腹壁收缩的阈值明显低于IBS-C组和对照组,不同容量扩张时腹部收缩次数明显高于IBS-C组和对照组,IBS-C的腹壁收缩的最小阈值明显高于对照组。IBS模型组下丘脑c-fos阳性细胞显著多于对照组,且IBS-D组多于IBS-C组。IBS模型组肌间神经丛中c-fos阳性细胞明显多于对照组。结论 IBS模型内脏敏感性的变化与脑-肠轴痛觉高敏感有一定的关系,肠神经丛初级感觉神经元的激活是IBS内脏高敏感的机制之一。

The brain-gut axis mechanism of visceral hypersensitivity of rats with irritable bowel syndrome

Objective To explore the visceral hypersensitivity mechanism in rats of different subtypes with irritable bowel syndrome(IBS) by observing the c-fos expression in the brain and gut.Methods Rat model of IBS-constipation(IBS-C) was established by stomach irrigation with 0-4 ℃ cool water whereas rat model of IBS-diarrhea(IBS-D) was established by instillation of acetic acid and restrain stress.All the rats were measured for the threshold value of balloon dilating rectum to cause abdominal contraction and abdominal contraction times of different balloon volume dilating rectum.The number of Fos positive cells in the hippocampus,hypothalamus,jejunum,ileum,proximate colon and distal colon was detected by immunohistochemical staining and analyzed semi-quantitatively by computerized color image analyzer respectively.Results The threshold volume of balloon causing abdominal contraction was significantly lower in IBS-D group than in IBS-C group and blank control group,while it was significantly higher in IBS-C group than in control group.Abdominal contraction times of different balloon volume dilating rectum were more in IBS-D group than in IBS-C group and control group.Immunohistochemical staining showed that Fos positive cells in the hypothalamus and myenteric plexus of both IBS-D and IBS-C groups outnumbered those of control group,and the number in the hypothalamus of IBS-D group was larger than that of IBS-C group.Conclusion The change of visceral hypersensitivity of rats with IBS is related to nociceptive high sensitivity in brain-gut axis,and the partial mechanism is the activation of the gut’s primary sensory neuron.