利培酮诱导大鼠便秘作用研究

发布时间：2018-03-23 21:42

本文选题：利培酮　切入点：平滑肌收缩　出处：《中国新药杂志》2017年04期

【摘要】：目的:探讨利培酮应用诱导大鼠便秘的作用及其相关机制。方法:离体实验研究利培酮对大鼠离体胃、空肠和结肠肌条收缩的作用;在体实验考察利培酮对大鼠排便习惯的作用;采用Western blot方法考察利培酮对炎症相关蛋白表达的作用。结果:在10~160μmol·L~(-1)剂量范围内,利培酮显著抑制大鼠离体胃,空肠和结肠平滑肌收缩,其中对空肠平滑肌的收缩性抑制作用最明显。灌胃(ig)利培酮2周的大鼠小肠组织中NO,前列腺素-2(PGE-2),肿瘤坏死因子(TNF-α),白细胞介素6(IL-6),白细胞介素1β(IL-1β)含量均显著增加。其机制可能与环氧合酶2(COX-2)以及核转录因子Kappa B(NF-κB),ERK蛋白的表达增加相关。结论:利培酮具有抑制大鼠胃肠动力的作用。同时慢性应用利培酮可通过ERK通路介导的NF-κB激活i NOS和COX-2,诱发炎症。本研究为揭示利培酮胃肠道的不良反应机制提供科学参考信息,为以后预防利培酮胃肠道不良反应提供临床依据。
[Abstract]:Objective: to investigate the effects of risperidone on constipation induced by risperidone in rats. Methods: the effects of risperidone on contraction of isolated gastric, jejunum and colonic muscle strips in rats were studied in vitro. The effect of risperidone on defecation habit of rats was investigated in vivo, and the effect of risperidone on the expression of inflammatory related protein was investigated by Western blot method. Results: Risperidone significantly inhibited the expression of inflammatory related protein in isolated rat stomach at the dose of 10 ~ 160 渭 mol / L ~ (-1). The smooth muscle of the jejunum and colon contracts, The contractile inhibition of jejunal smooth muscle was most obvious. The contents of no, prostaglandin 2, TNF- 伪, IL-6, IL-1 尾 in the small intestine of rats fed with risperidone for 2 weeks were significantly increased. The mechanism may be related to the increased expression of cyclooxygenase 2 (COX-2) and nuclear transcription factor Kappa BnNF- 魏 BnERK protein. Conclusion: risperidone can inhibit gastrointestinal motility in rats. Meanwhile, chronic risperidone can activate NF- 魏 B via ERK pathway. I NOS and COX-2, which induce inflammation. This study provides scientific reference information for revealing the mechanism of risperidone gastrointestinal adverse reactions. To provide a clinical basis for the prevention of risperidone gastrointestinal adverse reactions.
【作者单位】：天津中医药大学第一附属医院;天津市安定医院;
【分类号】：R574.62

【参考文献】