摘要
背景:临床研究发现,替加色罗可以明显改善肠易激综合征患者的腹部不适和腹痛,但其调节内脏感觉的机制目前尚不清楚。目的:观察替加色罗对结肠炎诱导的大鼠腰骶髓Fos、P物质(SP)和降钙素基因相关肽(CGRP)表达的影响,探讨替加色罗降低内脏敏感性的作用途径。方法:成年雄性Sprague-Dawley大鼠24只,以三硝基苯磺酸灌肠诱导结肠炎并随机分为实验组1:替加色罗灌胃,每天2mg/kg;实验组2:替加色罗灌胃,每天1mg/kg;对照组:生理盐水灌胃,2.0ml/d。连续灌胃7天后,采用免疫组化方法检测大鼠腰骶髓Fos、SP和CGRP的表达。结果:结肠炎可诱导对照组大鼠腰骶髓(L5～S1)背角深层Fos表达以及背角浅层SP和CGRP表达。实验组1大鼠腰骶髓背角Fos阳性神经元数(22.0±7.7)和SP密度(12.5%±1.4%)显著低于对照组(62.2±18.9和35.9%±8.9%,P<0.05),CGRP密度(1.2%±1.1%)与对照组(2.8%±2.4%)相比无显著差异。实验组2大鼠腰骶髓背角Fos、SP和CGRP的表达与对照组相比均无显著差异。结论:替加色罗可以明显减少结肠炎诱导的大鼠腰骶髓背角Fos和SP的表达,其降低内脏敏感性的作用可能与抑制脊髓背角SP的表达有关。
Background： In clinical studies, it has been found that tegaserod offered a rapid and sustained relief of abdominal discomfort/pain in patients with irritable bowel syndrome （IBS）. However, the mechanism of tegaserod in regulating visceral sensation is still unclarified. Aims： To observe the effects of tegaserod on expressions of Fos, substance P （SP） and calcitonin gene-related peptide （CGRP） induced by colonic inflammation of rats lumbosacral spinal cord, so as to appraise its pathway in reducing visceral sensitivity. Methods： The colitis model was induced by intraluminal administration of trinitrobenzenesulfonic acid （TNBS）, and 24 adult male Sprague-Dawley rats were divided randomly into three groups. Group h intragastric administration of tegaserod 2 mg/kg per day; Group 2： intragastric tegaserod, 1 mg/kg per day; Control group： intragastric saline, 2.0 ml/d. After 7 days of intragastric administration, the lumbosacral spinal cord was removed and processed, the expression of Fos, SP and CGRP were detected immunohistochemically. Results： In the control group, majority of Fos-labeled neurons was localized in the deeper laminae of dorsal horn of lumbosacral spinal cord （Ls-S0, while SP and CGRP were mainly expressed in the superficial laminae of dorsal horn after TNBS administration. Administration of tegaserod 2 mg/kg resulted in significant decrease of the number of Fos-labeled neurons （22.0±7.7） and SP density （12.5% ±1.4%） in the dorsal horn of lumbosacral spinal cord as compared with those of the control group （62.2±18.9 and 35.9%± 8.9%, P〈0.05）. However, no significant difference was found in the density of CGRP between group 1 and the control group （1.2%±1.1% vs. 2.8%±2.4%）. In group 2, neither Fos expression nor SP or CGRP density in the dorsal horn of lumbosacral spinal cord decreased significantly in comparison with those in the control group. Conclusions： Tegaserod can significantly decrease the colonic inflammation-induced Fos and SP expression in the dorsal horn of lumbosacral spinal cord in rats. It may reduce the visceral sensitivity by inhibiting SP expression in spinal dorsal horn.
出处
《胃肠病学》
2005年第4期203-207,共5页
Chinese Journal of Gastroenterology
