本研究旨在调查普鲁卡必利是否,作为5-羟色胺4(5-HT4)受体激动剂,通过促进糖尿病(DM)大鼠肠神经系统(ENS)的再生来改善肠运动。通过腹腔注射链脲佐菌素建立DM大鼠模型。将大鼠随机分为4组,每组6只:对照组,DM(DM模型),DM+A(5微克/千克普鲁卡必利)和DM+B(10微克/千克普鲁卡必利)。对照组大鼠给予等体积的柠檬酸溶剂。成功建立模型后,在服用普鲁卡必利之前,高血糖水平维持了2周。使用玻璃珠放电法测量结肠通过时间。结果表明,糖尿病大鼠的结肠运输时间最长,DM+B组明显缩短。随后,结肠被收集了。Nestin的表达水平,胶质纤维酸性蛋白(GFAP),SOX10,RNA结合蛋白人抗原D(HuD)和泛素硫酯酶(PGP9.5)通过免疫组织化学分析确定。进行5‑HT4+Nestin和Ki67+Nestin的免疫荧光双重染色。使用ELISA测量5‑HT水平。与对照组相比,Nestin表达在DM和DM+A组中显著增高,它集中在柱状上皮细胞和间充质中。此外,Nestin在DM+A组的表达水平高于DM组。在DM+B组和对照组之间没有观察到Nestin表达水平的差异。5-HT蛋白的表达水平在对照组中最高;然而,DM组中5-HT蛋白的表达水平,DM+A组和DM+B组呈增加趋势。没有观察到5‑HT4和Nestin表达的类似趋势;然而,Nestin和Ki67的表达趋势相似。GFAP的表达水平,DM+A组和DM+B组的SOX10、PGP9.5和Ki67均高于DM组。在DM+A组中,与对照组相比,HuD表达降低,但与DM组相比明显升高。总之,普鲁卡必利可能通过促进DM大鼠的ENS再生来改善肠道运动。
The present study aimed to investigate whether
prucalopride, as a 5‑hydroxytryptamine 4 (5‑HT4) receptor agonist, improved intestinal motility by promoting the regeneration of the enteric nervous system (ENS) in rats with diabetes mellitus (DM). A rat model of DM was established using an intraperitoneal injection of streptozotocin. The rats were randomly divided into four groups of 6 rats/group: Control, DM (DM model), DM + A (5 µg/kg
prucalopride) and DM + B (10 µg/kg
prucalopride). The rats in the Control group were given an equal volume of citric acid solvent. After successful model establishment, high blood glucose levels were maintained for 2 weeks before administration of
prucalopride. The colonic transit time was measured using the glass bead discharge method. It was revealed that the colonic transit time of diabetic rats was the longest, and this was significantly shortened in the DM + B group. Subsequently, the colons were collected. The expression levels of Nestin, glial fibrillary acidic protein (GFAP), SOX10, RNA‑binding protein human antigen D (HuD) and ubiquitin thiolesterase (PGP9.5) were determined via immunohistochemical analysis. Immunofluorescence double staining of 5‑HT4 + Nestin and Ki67 + Nestin was performed. The 5‑HT level was measured using ELISA. Compared with that in the control group, Nestin expression was significantly increased in the DM and DM + A groups, and it was concentrated in columnar epithelial cells and the mesenchyme. Furthermore, the expression levels of Nestin in the DM + A group were higher than those in the DM group. No difference was observed in the expression levels of Nestin between the DM + B group and the Control group. The expression levels of 5‑HT protein were highest in the Control group; however, the expression levels of 5‑HT protein in the DM group, DM + A group and DM + B group exhibited an increasing trend. Similar trends in the expression of 5‑HT4 and Nestin were not observed; however, similar trends in the expression of Nestin and Ki67 were observed. The expression levels of GFAP, SOX10, PGP9.5 and Ki67 in the DM + A and DM + B groups were higher compared with those in the DM group. In the DM + A group, HuD expression was decreased compared with that in the Control group but it was markedly higher compared with that in the DM group. In conclusion,
prucalopride may improve intestinal motility by promoting ENS regeneration in rats with DM.