长期服用普芦卡必利对慢传输型便秘雌性大鼠肠道组织及5-HT受体表达水平影响的研究

Effect of long-term administration of prucalopride on intestinal tissue and the expression levels of 5-HT receptors in female rats with slow transit constipation

摘要

目的 探究长期口服普芦卡必利对慢传输型便秘雌性大鼠肠道组织及5-HT受体表达水平的影响，为该药在临床治疗中的规范应用提供理论支持。 方法 选用成年雌性SD大鼠，将其随机分为正常组、模型组以及普芦卡必利（力洛）组，并进行为期2个月的干预。观察指标包括大鼠首次白便排出时间、粪便含水率、结肠含水量、肠道组织病理和黏液分泌情况，以及5-羟色胺（5-Hydroxytryptamine，5-HT）、5-羟色胺3受体（5-Hydroxytryptamine Receptor 3，5-HT3R）、5-羟色胺4受体（5-Hydroxytryptamine Receptor 4，5-HT4R）蛋白表达等变化。 结果 长期服用普芦卡必利显著改善了慢传输型便秘大鼠的排便时间、结肠含水量和粪便含水率等指标（P<0.05）。结肠病理组织染色和黏液染色结果表明，该药物能够改善大鼠结肠组织的病理状态和结肠黏液分泌情况。酶联免疫吸附（Enzyme-Linked Immunosorbent Assay，ELISA）和免疫组织化学（immunohistochemistry，IHC）检测显示，与模型组相比，力洛组的5-HT、5-HT3R、5-HT4R蛋白表达水平显著升高（P<0.05），而与空白组相比，力洛组的蛋白表达水平无显著差异（P>0.05）。 结论 长期服用普芦卡必利有助于改善慢传输型便秘模型大鼠的疾病状态、肠道组织病理状态和结肠黏液分泌情况，同时提高了5-HT受体的表达水平。

Abstract

Objective To investigate the impact of long-term oral administration of prucalopride on intestinal tissue and the expression levels of 5-HT receptors in female rats with slow transit constipation，and to provide theoretical support for the standardized application of this drug in clinical treatment. Methods Adult female Sprague-Dawley rats were selected and randomly divided into normal group，model group，and prucalopride（Resolor） group，and intervention was performed for 2 months. Related indicators were observed，including time to white stool discharge，fecal water content，colonic water content，intestinal histopathology and mucus secretion，and the expression of 5-HT，5-HT3R，and 5-HT4R. Results Long-term administration of prucalopride significantly improved defecation time，colonic water content，and fecal water content in rats with slow transit constipation（P<0.05）. Colonic pathological tissue staining and mucus staining showed that the drug could improve the pathological status of colonic tissue and colonic mucus secretion in rats. ELISA and IHC showed that compared with the model group，the Resolor group had significant increases in the protein expression levels of 5-HT，5-HT3R，and 5-HT4R（P<0.05），while there were no significant differences in protein expression levels between the Resolor group and the blank group（P>0.05）. Conclusion Long-term use of prucalopride helps to improve disease status，intestinal tissue pathology，and colonic mucus secretion in rats with slow transit constipation and increase the expression levels of 5-HT receptors.

关键词

普芦卡必利 / 慢传输型便秘 / 5-羟色胺 / 5-羟色胺3受体 / 5-羟色胺4受体

Key words

prucalopride / slow transit constipation / 5-HT / 5-HT3R / 5-HT4R

基金资助

贵州省卫生健康委科学技术基金资助项目(gawkj2021-223)