枳实水提物对大鼠泻剂结肠肠壁神经丛的影响及机制研究

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目的:探讨枳实水提物对胃肠道动力的兴奋作用是否有5-羟色胺4受体(5-HTR4)的参与,以及其与5-HTR4激动剂是否在泻剂结肠大鼠肠壁神经网络的重塑中发挥作用。方法:应用大黄建立泻剂结肠大鼠模型,随后分组予莫沙必利及不同剂量的枳实水提物灌胃治疗,持续14d。以墨汁推进试验测定其传输功能;留取结肠组织,采用透射电镜观察各组大鼠结肠组织的超微结构;Real-time PCR、Western blot及免疫组化测定5-HTR4高分子量神经丝(NF-H)mRNA/蛋白的表达水平。结果:1莫沙必利及枳实水提物高剂量组可显著改善泻剂结肠大鼠的肠道动力;2模型组、莫沙必利组及中药各剂量组结肠超微结构均出现不同程度的神经元退行性病变;3莫沙必利可上调5-HTR4蛋白质的表达,与mRNA水平呈同步变化;而枳实水提物上调5-HTR4 mRNA转录水平的同时并未使其蛋白质的表达增加。莫沙必利及枳实水提物高剂量组均可上调NF-H mRNA及蛋白质的表达。结论:莫沙必利通过兴奋5-HTR4受体增强慢传输型便秘大鼠模型结肠动力的同时,还能起到修复泻剂结肠肠壁肌间NF-H的作用。而枳实水提物促结肠动力的机制主要是通过促进NF-H生长实现的,5-HTR4是其作用的一个分子靶标,但可能不是发挥生物学活性的主要途径。 Objective: To investigate whether the excitatory effect of water extract of Fructus Aurantii on gastrointestinal motility has the participation of 5-hydroxytryptamine 4 receptor (5-HTR4) and whether it is associated with 5-HTR4 agonist in the intestinal wall nerves of laxative colon Network remodeling play a role. Methods: The rhubarb was used to establish the model of cathartic colon, then sub-treated with mosapride and different doses of citrus aurantium water extract for 14 days. The ultrastructure of colon in each group was observed by transmission electron microscope (TEM). The expression of 5-HTR4 high-molecular-weight neurofilament -H) mRNA / protein expression level. Results: 1 Mosapride and Citrus aurantium water extract high-dose group can significantly improve the intestinal motility of colon cathartic; 2 model group, mosapride group and traditional Chinese medicine dose group colon ultrastructures are different Level of neuron degeneration.3 Mosapride up-regulated the expression of 5-HTR4 protein in synchronization with mRNA level. However, the water extract of Fructus Aurantii up-regulated the transcription of 5-HTR4 mRNA, Increased expression. Mosapride and citrus aurantium water extract high-dose group can up-regulate NF-H mRNA and protein expression. CONCLUSIONS: Mosapride can also stimulate NF-H in the intestinal wall muscle of laxatives by stimulating the 5-HTR4 receptor in the colon of slow transit constipation rats. However, the mechanism of aqueous extract of Fructus Immaturei promoting colonic motility is mainly through promoting the growth of NF-H, 5-HTR4 is a molecular target of its action, but may not be the main way to exert its biological activity.
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