替加色罗对内脏高敏性大鼠直肠扩张后脊髓c-Fos表达的影响

Effects of tegaserod on spinal c-Fos expression in rats with visceral hypersensitivity after rectal distention

目的 研究替加色罗对大鼠内脏敏感性的作用。方法 新生SD大鼠出生后第 8至 2 1天予醋酸灌肠 ,建立慢性内脏高敏模型为H组 ;生理盐水灌肠为C组。待大鼠成年后 ,将H组分为H病理 、H盐水 、H溶剂 、HTeg0 .1、HTeg0 .3 和HTeg1.0 组 ;C组分为C病理 、C盐水 和CTeg1.0 组。H病理 和C病理 组不扩张直肠行病理学检查和髓过氧化物酶活性测定 ;H盐水 和C盐水 组腹腔注射生理盐水 ,H溶剂 组注射溶剂 +蒸馏水 ,HTeg0 .1、HTeg0 .3 和HTeg1.0 组分别注射替加色罗 0 .1、0 .3、1.0mg/kg ,CTeg1.0 组注射替加色罗 1.0mg/kg ,直肠球囊快速注水 (0 .4、0 .8、1.2ml)扩张观肠道 ,每次扩张持续 2 0s,间隔 5min ,察腹部撤离反射 (AWR)和脊髓 (L6～S1)c Fos表达。结果 H盐水 与H溶剂 组AWR积分明显高于其他组 (P <0 .0 5 ) ,腰骶髓c Fos阳性细胞总数明显增加 ,两组间无明显差异。HTeg0 .1、HTeg0 .3 和HTeg1.0 组比H盐水 组AWR积分明显降低 ,c Fos阳性细胞减少 (182± 14 ,16 6± 17,12 8± 15比 2 13± 13;P <0 .0 5 )。结论 替加色罗可明显降低内脏高敏大鼠的内脏敏感性 ,并剂量依赖性地减少脊髓c

Objective To assess the effects of tegaserod on rat with visceral hypersensitivity. Methods Neonatal SD rats were randomized to receive colonic acetic acid irritation between postnatal days 8 and 21 as visceral hypersensitive model (Group H) or by saline intrarectally as control group (Group C). While rats were grown-up, rectal distention (RD) was performed by a balloon rapidly inflated with increasing volumes of saline (0.4, 0.8 and 1.2 ml) for 20 seconds at five-minute intervals. The 5 subgroups of Group H were injected randomly with saline, vehicle (1-methyl-2-thpyrrolidone) or tegaserod at doses of 0.1, 0.3 and 1 mg/kg i.p., respectively. The 2 subgroups of Group C were injected with saline or tegaserod at dose of 1 mg/kg i.p.. RD was performed 10 min after injection and abdominal withdrawal reflex (AWR) was recorded, and then c-Fos expression in spinal cord (L6-S1) was analyzed quantitatively by immunohistochemistry. Results 1) Compared to saline, vehicle did not affect AWR and c-Fos expression. 2) Compared to saline, tegaserod significantly (P<0.05) inhibited AWR in Group H, but had no significant effect in Group C. Tegaserod ( 1.0 mg/kg) inhibited AWR more significantly in Group H than in Group C at the group largest volume of distention (1.2 ml). 3) Compared to saline, tegaserod dose-dependently attenuated c-Fos expression in Group H (213±13 vs. 182±14, 166±17 and 128±15; P<0.05) and in Group C (163±18 vs. 142±14; P<0.05).Conclusion Tegaserod inhibits response activity to rectal distention in rats with visceral hypersensitivity and dose-dependently attenuates spinal c-Fos expression.