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丙酮酸钙在二乙基亚硝胺诱导的大鼠肠易激综合征模型中发挥有益作用。

Calcium Pyruvate Exerts Beneficial Effects in an Experimental Model of Irritable Bowel Disease Induced by DCA in Rats.

机构信息

CIBER-EHD, Department of Pharmacology, Center for Biomedical Research (CIBM), University of Granada, 18071 Granada, Spain.

Instituto de Investigación Biosanitaria de Granada (ibs.GRANADA), 18012 Granada, Spain.

出版信息

Nutrients. 2019 Jan 10;11(1):140. doi: 10.3390/nu11010140.

Abstract

Pyruvate is a normal constituent of the body that participates in carbohydrate metabolism and functions as a scavenger of free radicals. Calcium pyruvate monohydrate (CPM) is a more stable derivative that has proved its anti-inflammatory effect in experimental colitis, among other disorders, and that could also be considered a source of calcium. Thus, it would be useful for the treatment of diseases with an inflammatory component and a high prevalence of osteoporosis like the irritable bowel syndrome (IBS). The aim of the present study is to evaluate the effects of CPM in a rat model of chronic post-inflammatory visceral pain induced by deoxycholic acid (DCA) that resembles IBS. Rats were administered DCA for three days intracolonically and then treated daily with CPM (40 and 100 mg/kg) or gabapentin (70 mg/kg) (positive control) by oral gavage for 17 days. The treatments reduced the visceral hypersensitivity measured by response to colorectal distension and referred pain. DCA induced changes in the colonic immune response characterized by increased expression of the cytokine and the inducible enzyme , which was reduced by the treatments. DCA also decreased the gut expression of the mucins and , which was normalized by CPM, whereas gabapentin only increased significantly . Moreover, DCA increased the expression of , which was decreased to basal levels by all the treatments. However, the serotonin receptor , which was also elevated, was not affected by any of the treatments, indicating no effect through this signalling pathway. In conclusion, CPM ameliorated the visceral hypersensitivity and the referred pain caused by DCA, being as effective as the control drug. Furthermore, it improved the immune status of the animals, which could contribute to the visceral analgesia and the regeneration of the intestinal epithelial barrier integrity.

摘要

丙酮酸是人体的正常组成部分,参与碳水化合物代谢,作为自由基的清除剂。丙酮酸钙一水合物(CPM)是一种更稳定的衍生物,已被证明在实验性结肠炎等疾病中具有抗炎作用,并且也可以被认为是钙的来源。因此,它对于治疗具有炎症成分和骨质疏松症高发的疾病(如肠易激综合征(IBS))可能是有用的。本研究的目的是评估 CPM 在脱氧胆酸(DCA)诱导的慢性炎症后内脏疼痛大鼠模型中的作用,该模型类似于 IBS。大鼠经结肠内给予 DCA 三天,然后每天通过口服灌胃给予 CPM(40 和 100 mg/kg)或加巴喷丁(70 mg/kg)(阳性对照)治疗 17 天。这些治疗方法降低了通过结肠扩张和牵涉痛测量的内脏高敏性。DCA 诱导的结肠免疫反应改变,特征为细胞因子 和诱导型酶 的表达增加,这些改变被治疗方法所降低。DCA 还降低了肠道黏蛋白 和 的表达,CPM 使其恢复正常,而加巴喷丁仅显著增加 。此外,DCA 增加了 的表达,所有治疗均将其降低至基础水平。然而,DCA 还增加了 5-羟色胺受体 的表达,所有治疗均未对此产生影响,表明该信号通路无作用。总之,CPM 改善了 DCA 引起的内脏高敏性和牵涉痛,与对照药物一样有效。此外,它改善了动物的免疫状态,这可能有助于内脏镇痛和肠道上皮屏障完整性的再生。

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