【作者】 巩倩；

【导师】 李永渝；

【作者基本信息】 同济大学 ， 病理学与病理生理学， 2007， 硕士

【摘要】 目的探讨不同浓度的草药复方制剂STW-5-NⅡ对不同化学物及机械刺激诱导的大鼠小肠传入神经电活动变化的影响,并分析其可能的机制。方法24只雄性Wister大鼠均分为4组,动物麻醉后经胃管灌入不同浓度STW-5-NⅡ药液（原液、50%原液、25%原液）及对照液。用细胞外多元肠系膜传入神经记录技术（extracellular multi-unit mesenteric afferent nerverecording）描记肠传入神经元电活动信号。给予不同剂量5-羟色胺（5-HT）（5,10,20,40μg/kg）或不同剂量缓激肽（BK）（15,30,60μg/kg）静脉注射,以及不同程度的肠管扩张（0cmH₂O～60cmH₂O）刺激,观察各种刺激前后小肠传入神经电活动的变化,比较和分析不同浓度STW-5-NⅡ对此变化的影响。结果STW-5-NⅡ对小肠传入神经基本电活动没有影响。不同剂量的5-HT和BK均可引起小肠传入神经电活动的增加;中、高浓度的STW-5-NⅡ明显降低BK的这种增加作用（P＜0.05,或P＜0.01）;肠管扩张刺激在20-60cmH₂O时小肠传入神经电活动增加,不同浓度的STW-5-NⅡ对此有降低作用,对5-HT诱导的小肠传入神经电活动的增加也有降低的趋势,但作用不明显（P＞0.05）。结论STW-5-NⅡ可以降低大鼠小肠对某些化学刺激和机械刺激的敏感性,可能有助于与内脏敏感性增高有关的胃肠道运动功能障碍性疾病的治疗。目的:研究大麻素受体激动剂、拮抗剂对高敏感小肠传入神经电活动的影响,对大鼠小肠平滑肌电活动的影响,以探讨内源性大麻素系统对胃肠运动的作用。方法:离体试验:将雄性Wistar大鼠麻醉后取空肠肠管,用细胞外多元肠系膜传入神经记录技术（extracellular multi-unit mesenteric afferent nerve recording）描记肠传入神经元电活动信号。然后肠管灌流大麻素受体激动剂(Win55,10^-5mol/L)或拮抗剂(SR141716A,10^-5mol/L),给予5-羟色胺（5-HT,500μM）、缓激肽（BK,1μM）或不同程度的肠管扩张（0cmH₂O～80cmH₂O）刺激,观察各刺激前后小肠传入神经电活动的变化。在体试验:用PowerLab微电极法,描记大鼠胃肠平滑肌电活动,大麻素受体激动剂（HU210,100μg/kg）或拮抗剂（AM251,3mg/kg）腹腔注射,观察大鼠胃肠平滑肌电活动的变化。结果:大麻素受体拮抗剂SR141716A(10^-5mol/L)明显降低肠管扩张（30cmH₂O～80cmH₂O）以及BK（1μM）诱导的离体小肠传入神经电活动的增加（P＜0.05）,而大麻素受体激动剂Win55对此类化学、机械刺激诱发的小肠传入神经电活动无明显影响;SR141716A的类似物AM251（3mg/kg）明显增强在体大鼠小肠平滑肌峰电活动的频率及幅度,而大麻素受体激动剂HU210（100μg/kg）则明显降低在体大鼠小肠平滑肌峰电活动的频率及幅度。结论:内源性大麻素系统参与大鼠胃肠运动的调节。在整体状态下,该系统对大鼠小肠平滑肌峰电活动起抑制作用;对离体肠管,大麻素受体拮抗剂以及大麻素受体激动剂对其传入神经基础电活动没有明显影响,但某些病因引起的肠管传入神经电活动的增加（高敏感状态）受大麻素受体拮抗剂所抑制,提示局部大麻素系统活动增强可能参与了肠道高敏感的发生。更多还原

【Abstract】 Objective:To investigate the effect of different concentration of a new simplified herbal combination product STW-5-NII on intestinal afferent nerve discharge after different mechanical and chemical stimuli.Methods:24 male Wister Rats were divided into four groups.STW-5-NII at a concentration of 100%,50%,25%or vehicle were administered orally in rats after anesthetized.The extracellular multi-unit mesenteric afferent nerve recordings were obtained in the proximal jejunum.Afferent discharge to 5-Hydroxytryptamine（5-HT） (5、10、20 and 40μg kg^-1,i.v.),bradykinin（BK）(15、30 and 60μg kg^-1i.v.)and luminal distension（0cmH₂O -60cmH₂O）were recorded and analyzed.Results:Afferent nerve discharge was increased after different dose of 5-HT and BK. Afferent nerve sensitivity to bradykinin but not to 5-HT was significantly different depending on the dose of pretreatment with STW-5-NII.A pressure-dependent increase in afferent nerve discharge was observed during intraluminal distension that was not significant different following pretreatment with any concentraction of STW-5-NII.Conclusions:The herbal preparation STW-5-NII desensitized intestinal afferents selectively to systemic bradykinin.This new preparation might be helpful for patients suffering from disorders associated with visceral hypersensitivity. Objective To investigate the effects of CB agonist and antagonist on the afferent nerve discharge in the intestinal experimental hypersensitivity and the intestinal myoelectric activity in rats.Methods Experiment in vitro:Wistar rats were anesthetized and ileal segments removed with the mesenteric arcade attached.The segments were perfused with Krebs’ buffer（37℃）which was either supplemented with the CB-1 receptor agonist WIN 55,212-2(10^-5mold),or the CB-1 receptor antagonist SR 141716A(10^-5mol/l), or vehicle,respectively,（n=6,each）.The changes of intestinal afferent discharge were observed after adding 5-HT（500μM）or BK（1μM）or luminal distension（0 cmH₂O～80cmH₂O）.The afferent nerve discharge was recorded using extracellular multi-unit mesenteric afferent nerve recording.Experiment in vivo:SD rat intestinal myoelectric motility was recorded using PowerLab system（Australia）,and the effect of CB receptor agonist HU210（100μg/kg）or CB receptor antagonist AM 251（3mg/kg）was observed after their intraperitoneal injection respectively（n=6, each）.Results in vitro:Using CB-1 receptor antagonist SR141716A,the intestinal afferent nerve discharge induced by bradykinin stimulation was reduced significantly （P＜0.05）,and the same effect was also found in the afferent nerve discharge induced by the noxious mechanical distension of the intestinal loop（30 to 80cmH₂O） （P＜0.05）.in vivo:CB receptor antagonist AM 251（3mg/kg）increased the frequencies and amplitudes of the intestinal spike activities in rats.While CB receptor agonist HU210（100μg/kg）got the oppositive effection on the frequencies and amplitudes of the intestinal myoelectric activities in rats.Conclusion The endocannabinoid system took part in the regulation of the gastrointestinal motility.This system seemed to play an inhibiting role in the intestinal myoelectric activity in rats.It had no effect on the baseline of the afferent discharge from the isolated intestinal segments of rats.But the increment of the afferent discharge induced by some stimulatiors was attenuated by the CB antagonist significantly,which suggested that the increased activity of the local endocannabinoid system may be involved in the pathogenesis of the small intestinal hypersensitivity.更多还原