脑-肠互动指向性条件应激肠易激综合征动物模型的建立  

Development of irritable bowel syndrome animal model induced by brain gut interaction directed conditioned stress

作　　者：王伟岸[1] 钱家鸣[1] 潘国宗[1] 温淑豪[1] 张艳萍[2] 

机构地区：[1]中国医学科学院中国协和医科大学北京协和医院消化科 [2]中国医学科学院基础医学研究所动物实验中心

出　　处：《中华消化杂志》2004年第10期590-593,共4页Chinese Journal of Digestion

摘　　要：目的建立在肠易激综合征(IBS)发病中符合心理和胃肠生理因素互动特征的动物模型。方法Ⅱ级成年雄性Wistar大鼠作为模型动物,以樟脑丸特殊气味为条件刺激,肢体束缚加结直肠伤害性扩张刺激(气囊内压力>60mmHg)为非条件刺激,建立脑肠互动指向性条件应激肠功能紊乱模型。以cFos表达为标志,研究条件应激过程中的脑活化部位,并观测应激前30min侧脑室注射促皮质释放因子拮抗剂CRF941对内脏功能的影响。结果条件刺激和非条件刺激结合3次后,条件刺激即可稳定地诱发模型动物肠功能紊乱,持续达2h以上。与对照组相比,条件刺激后2h腹壁自发电活动增强[(5.50±0.55)次/5min比(0.83±0.75)次/5min,P<0.01];与对照组[(1.8±0.6)次/5min]相比,条件应激组近端结肠峰电位增多[(5.7±1.5)次/5min,P<0.01]。条件应激后1h大脑皮层多个部位cFos表达显著升高,其中与对照组[(2.4±1.1/HP)]相比,额前皮质在条件应激组[(30.6±11.5)/HP]和应激组[(35.6±13.5)/HP]表达显著增高(P<0.05)。在条件应激前30min侧脑室注射CRF9415μg,显著抑制条件应激诱发的内脏敏感性反应[(5.6±0.9)次/5min比(1.8±0.5)/次5min,P<0.01]。结论脑肠互动指向性条件应激可稳定诱发符合IBS发病特征的内脏功能紊乱。Objective To establish the animal model of irritable bowel syndrome (IBS) fulfilled the pathophysiological features of interaction between psychological factors and gastrointestinal physiological activity. Methods Adult male grade Ⅱ Wistar rats were used as experimental animal. Based on classical theory of conditioned reflex, the specific smell of camphor was used as conditioned stimulus, noxious colorectal distention (pressure in balloon > 60 mm Hg) and strained stress were used as non conditioned stimuli, a new bowel dysfunction animal model was developed. As a brain activation marker, c Fos expression during conditioned stress in special brain loci was investigated, and the effect of CRF 9 41 injection intracerebroventricularly was also evaluated 30 minutes before conditioned stress on visceral sensation. Results Conditioned stress, combined with non conditioned stressors for three times, induced steadily gastrointestinal dysfunction in animal lasting for more than 2 h. Comparison with controls, the activity of abdominal muscle in conditioned stress rats at 2 h after stress manifested as visceral hypersensitivity[(5.50±0.55)/5 min vs(0.83±0.75)/5 min, P <0.01] and proximal colon spike increased[(5.7±1.5) /5 min vs (1.8±0.6)/ 5 min, P <0.01]. The total sums of c Fos expression in many brain loci increased significantly in conditioned stress animals 1 h after stress, especially in prefrontal cortex[(30.6±11.5)/HP in conditioned stress rats, (35.6±13.5 )/HP in stress rats] compared that in controls( P <0.01)respectively. Administration of CRF 9 41 significantly reduced the conditioned stress induced visceral response [(5.6±0.9 )/5 min vs (1.8±0.5)5 min, P < 0.01 ]. Conclusion Brain gut interaction directed conditioned stress may induce bowel dysfunction fulfilled steadily IBS features in animals. This model would be suitable for the study of brain gut interaction in the pathogenesis of IBS.

关 键 词：应激 条件刺激 对照组 诱发 IBS 肠易激综合征 动物模型 峰电位 雄性 侧脑室注射 

分 类 号：R-332[医药卫生]