替加色罗对内脏感觉过敏大鼠模型的抗伤害性感觉作用

The anti-nociceptive property of tegaserod on rat model of visceral hypersensitivity

目的 了解结直肠机械刺激对大鼠内脏感觉功能的影响以及替加色罗对大鼠内脏感觉功能的调节作用。方法 8～ 2 1日龄大鼠每天行结直肠扩张 (CRD组 ,压力 6 0mmHg) ,对照组仅用导管在肛门周围轻微接触。 8～ 1 0周龄时用自制气囊扩张大鼠降结肠和直肠 ,观察动物的腹壁回撤反射(AWR)以测定内脏感觉。选取 8～ 1 0周龄的雄性大鼠分为CRD组、对照组和溶媒对照组 ,观察腹腔注射替加色罗前后的AWR评分。结果 扩张压力与AWR评分显著相关 (P <0 .0 1 ) ;CRD组在 4 0、6 0、80mmHg的压力扩张下 ,AWR评分明显高于对照组 (1 .96± 0 .1 6比 1 .36± 0 .1 6、2 .82± 0 .1 3比 2 .1 7± 0 .1 4、3.2 1± 0 .1 4比 2 .5 9± 0 .1 4 ,P <0 .0 1 ) ;在 4 0、6 0、80mmHg扩张压力下 ,CRD组的AWR评分在用替加色罗后较用药前明显降低 (1 .95± 0 .5 0比 1 .32± 0 .5 5、3.0 5± 0 .4 8比 2 .32± 0 .5 4、3.2 5± 0 .6 3比 2 .77± 0 .5 1 ,P <0 .0 5 ) ;对照组和溶媒对照组的AWR评分在用药前后差异无显著性。结论 新生大鼠给予结直肠机械刺激在成年后可导致慢性内脏感觉过敏 ;替加色罗通过提高对结直肠扩张的疼痛阈值 。

Objective To investigate the effects of colorectal dilatation on visceral sensation and the role of tegaserod in regulating visceral sensitivity in rats. Methods In study group, SD rats during postnatal days 8 to 21 were received balloon colorectal distension (CRD) every day (pressure 60 mm Hg), while in the control group, merely using catheter to touch perianus lightly. During postnatal 8 to 10 weeks, the rats were studied by using self made balloon to distend descending colon and rectum. In addition, the abdominal withdrawal reflex (AWR) was observed, and visceral sensation was measured. SD rats between postnatal 8 and 10 weeks were divided into CRD group, control group, and vehicle group. The AWR scores of three groups were recorded before and after intraperitoneal administration of tegaserod. Results There was significant correlation between distension pressure and AWR scores( P <0.01). At pressure 40, 60 and 80 mm Hg, the AWR scores in rats with CRD were significantly higher than that in control group (1.96±0.16 vs. 1.36±0.16, 2.82± 0.13 vs. 2.17±0.14, 3.21 ±0.14 vs. 2.59±0.14, P <0.01). Compared with the vehicle or control, tegaserod significantly reduced the AWR scores at the does of 0.3 mg/kg when the distension pressure was 40, 60 and 80 mm Hg (1.95±0.50 vs. 1.32±0.55, 3.05±0.48 vs. 2.32±0.54, 3.25±0.63 vs. 2.77 ±0.51, P <0.05). There was no significant difference between the AWR scores of control group and vehicle group before or after intraperitoneal administration of tegaserod. Conclusion With colon mechanical irritation during the periods of postnatal development, the adult rats can develop chronic visceral hypersensitivity. Tegaserod has an anti nociceptive property on visceral sensitivity by increasing pain threshold to CRD group.