Coutinho S V, Meller S T, Gebhart G F
Department of Pharmacology, University of Iowa, Iowa City 52242, USA.
Brain Res. 1996 Oct 14;736(1-2):7-15. doi: 10.1016/0006-8993(96)00661-0.
The present study examined the effects of colonic inflammation on reflex responses to colorectal distension (CRD) in awake rats. Visceromotor responses (VMR) to CRD were recorded in rats that received either no treatment or intracolonic saline or zymosan. Three hours following zymosan treatment (25 mg/ml; 1 ml) VMR response magnitudes were significantly increased at all intensities of CRD tested (10-80 mmHg). The enhanced responses to CRD were attenuated in a dose-dependent fashion by intrathecal administration of the non-competitive N-methyl-D-aspartate (NMDA) receptor channel blocker MK-801 to 60% of control and by the non-NMDA receptor antagonist DNQX to less than 20% of control. The metabotropic receptor antagonist AP-3 was without effect. Signs of multi-focal colonic inflammation were clearly present 3 h after zymosan treatment, characterized by an ingress of inflammatory cells and damaged crypts in and around these foci. Taken together these findings suggest that tissue inflammation increases the sensitivity of the colon to mechanical stimuli, leading to enhanced responses to CRD. This enhancement involves the activation of spinal NMDA as well as non-NMDA receptors, but not metabotropic receptors.
本研究检测了结肠炎症对清醒大鼠结直肠扩张（CRD）反射反应的影响。记录了未接受任何处理、接受结肠内注射生理盐水或酵母聚糖的大鼠对CRD的内脏运动反应（VMR）。酵母聚糖处理（25mg/ml；1ml）3小时后，在所有测试的CRD强度（10 - 80mmHg）下，VMR反应幅度均显著增加。鞘内注射非竞争性N - 甲基 - D - 天冬氨酸（NMDA）受体通道阻滞剂MK - 801，可使对CRD增强的反应以剂量依赖方式减弱至对照的60%，而注射非NMDA受体拮抗剂DNQX可使其减弱至对照的20%以下。代谢型受体拮抗剂AP - 3则无此作用。酵母聚糖处理3小时后，明显出现多灶性结肠炎症迹象，其特征为炎症细胞浸润以及这些病灶及其周围隐窝受损。综上所述，这些发现表明组织炎症会增加结肠对机械刺激的敏感性，导致对CRD的反应增强。这种增强涉及脊髓NMDA以及非NMDA受体的激活，但不涉及代谢型受体。
