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普瑞巴林通过抑制 microRNA-155 减轻葡聚糖硫酸钠诱导的小鼠结肠炎。

Pristimerin reduces dextran sulfate sodium-induced colitis in mice by inhibiting microRNA-155.

机构信息

Renmin Hospital of Wuhan University, Hubei Key Laboratory of Digestive System Disease, Wuhan 430060, Hubei Province, China.

Renmin Hospital of Wuhan University, Wuhan 430060, Hubei Province, China.

出版信息

Int Immunopharmacol. 2021 May;94:107491. doi: 10.1016/j.intimp.2021.107491. Epub 2021 Mar 23.

Abstract

Pristimerin (Pris), which is a natural triterpenoid compound extracted from the Celastraceae plant, has an effect on intestinal inflammation, but its mechanism needs further study. Human genome-wide analysis found that the expression of microRNA-155 in the blood and colon tissue of patients with IBD was increased. Therefore, we studied the effect of Pris on a model of DSS-induced colitis in mice and investigated whether Pris inhibited the expression of microRNA-155. We obtained a mouse model of acute experimental colitis by allowing the mice to drink a 3% by mass DSS solution freely for 7 days. Pris solutions at different concentrations were injected via the abdomen to simulate the therapeutic effect of Pris on colitis. The body weight and faeces were measured and recorded daily. The mice were sacrificed by the cervical dislocation method after the experiment, and the colon length and histological changes, as well as the changes in Nrf2 in the colon tissue, were measured. The activities of the antioxidant enzymes GSH, GSH-Px and SOD were examined. The expression levels of microRNA-155, IL-1β, IL-6, IL-17, and TNF-α in the colon were detected by RT-PCR technology, and the expression of NF-κB p65 in the colon was detected by western blotting. Our study shows that Pris can reduce the DAI score, obviously alleviate weight loss, and decrease the colon pathological tissue damage caused by DSS. Pris can inhibit the increase in microRNA-155 expression induced by DSS-induced colitis. Our study has shown that Pris may reduce DSS-induced colitis in mice by inhibiting the expression of microRNA-155, and further inhibition of the inflammatory response and oxidative stress occurred.

摘要

棓丙酯(Pris)是从卫矛科植物中提取的一种天然三萜类化合物,对肠道炎症有作用,但作用机制尚需进一步研究。人类全基因组分析发现,IBD 患者血液和结肠组织中 microRNA-155 的表达增加。因此,我们研究了 Pris 对 DSS 诱导的结肠炎小鼠模型的作用,并探讨了 Pris 是否抑制 microRNA-155 的表达。我们通过让小鼠自由饮用 3%质量 DSS 溶液 7 天,获得了急性实验性结肠炎的小鼠模型。通过腹部注射不同浓度的 Pris 溶液模拟 Pris 对结肠炎的治疗作用。每天测量和记录体重和粪便。实验结束后,采用颈椎脱位法处死小鼠,测量和记录结肠长度和组织学变化,以及结肠组织中 Nrf2 的变化。检测抗氧化酶 GSH、GSH-Px 和 SOD 的活性。通过 RT-PCR 技术检测结肠中 microRNA-155、IL-1β、IL-6、IL-17 和 TNF-α 的表达水平,通过 Western blot 检测结肠中 NF-κB p65 的表达。我们的研究表明,Pris 可以降低 DAI 评分,明显减轻体重减轻,并减少 DSS 引起的结肠病理组织损伤。Pris 可以抑制 DSS 诱导的结肠炎引起的 microRNA-155 表达增加。我们的研究表明,Pris 可能通过抑制 microRNA-155 的表达来减轻 DSS 诱导的结肠炎,从而进一步抑制炎症反应和氧化应激的发生。

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