替加色罗对结肠炎大鼠内脏敏感性的影响及其与结肠内P物质和降钙素基因相关肽表达的关系

目的评价替加色罗对结肠炎大鼠内脏敏感性的影响,并探讨其调节内脏敏感性的作用途径。方法成年雄性SD大鼠42只,经三硝基苯磺酸(TNBS)灌肠诱导结肠炎后随机分为4个实验组和4个对照组:其中3个结-直肠扩张(CRD)实验组(n=6)及3个CRD对照组(n=4)分别给大鼠替加色罗和生理盐水灌胃,在灌胃3、7、14 d后记录腹壁肌电活动;1个免疫组化(IH)实验组(n=6)及其对照组(n=6)分别在替加色罗和生理盐水灌胃7d后,采用免疫组织化学法观察大鼠结肠内P物质(SP)和降钙素基因相关肽(CGRP)的表达。结果替加色罗灌胃3 d后,在1.2、1.6mL扩张容量下,大鼠腹肌收缩次数(6.00±1.10,3.17±0.98)较对照组明显减少(9.50±2.52,13.0±2.31,P<0.05)。替加色罗连续灌胃7 d和14 d后,在0.4、0.8、1.2、1.6 mL扩张容量下,大鼠腹肌收缩次数均明显少于对照组(P<0.01)。替加色罗灌胃7 d后,结肠内SP染色评分下降,而CGRP染色强度与对照组比较无明显变化。结论替加色罗可以明显降低结肠炎大鼠对结肠球囊扩张刺激的敏感性,其降低内脏敏感性的作用可能与其抑制胃肠道内脏感觉传入神经表达SP有关。

Effects of tegaserod on visceral sensitivity and expression of SP and CGRP in the rat colon

Objective To investigate the effects of tegaserod on visceral sensitivity and explore the regulating mechanism.Methods Forty-two male Spragre-Dawley rats,which were induced colonic inflammation by intraluminal administration of trinitrobenzenesulfonic acid(TNBS),were randomly divided into eight groups.In the three colorectal distention(CRD) treated groups(n=6),abdominal contractions were recorded after 3,7 and 14 days of intra-gastric administration of tegaserod 2mg/kg d.In the three CRD control groups(n=4),abdominal contractions were recorded after 3,7 and 14 days of intra-gastric injection of saline 2.0mL/d.In immunohistochemistry(IH) treated group(n=6) and IH control group(n=6),samples of colon were removed and processed for SP and CGRP immunohistochemistry after 7 days of intra-gastric administration of tegaserod and saline,respectively.Results Abdominal contractions induced by colonic distention decreased significantly at 1.2mL and 1.6mL distention volume after 3 days of tegaserod administration(P<0.05).After 7 and 14 days of intra-gastric administration of tegaserod,abdominal contractions decreased significantly at 0.4,0.8,1.2mL and 1.6mL distention volume compared with those of the control rats(P<0.01).In the rats treated with tegaserod for 7 days,the scoring of substance P in the colon reduced significantly.However,staining of CGRP in the colon did not significantly decrease.Conclusion Tegaserod can significantly reduce visceral sensitivity to colonic distention in conscious rats.It may reduce visceral sensitivity by inhibiting SP expression of the primary visceral afferents in the colon.