Department of Gastroenterology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China.
Department of Physiology and Neurobiology, School of Basic Medicine Sciences, Zhengzhou University, Zhengzhou, China.
Fundam Clin Pharmacol. 2021 Oct;35(5):852-860. doi: 10.1111/fcp.12650. Epub 2021 Mar 4.
Ulcerative colitis is a chronic inflammatory bowel disorder, which is having higher mortality rate. The present report evaluates the protective effect of miR-199a-3p oligomer for the treatment of Ulcerative colitis (UC). Ulcerative colitis was induced by administration of dextran sulfate sodium [DSS (3%)] with drinking water for the duration of one week in mice and miR-199a-3p oligomer was treated for the same duration. Effect of miR-199a-3p oligomer was determined by estimating the body weight, blood stool and length of colon in UC mice. Inflammatory cytokines, oxidative stress parameters and Treg/Th17 ratio was determined in the serum, intestinal and spleen tissue of UC mice. mRNA expression of TGFβ, Foxp3, RORγt and STAT3 was estimated in the intestinal tissue of UC mice. Moreover, permeability of intestine was determined by estimating the expression of FITC-dextran in the serum and expression of junction protein in the tissue of UC mice. The data of the study suggest that treatment with miR-199a-3p oligomer ameliorates the altered condition in ulcerative colitis mice. There was reduction in the level of cytokines and parameters of oxidative stress in the intestine of miR-199a-3p oligomer than UC group. Moreover, intestinal permeability was enhanced in miR-199a-3p oligomer treated UC mice. The level of Th17 in the serum and mRNA expression of TGFβ, Foxp3, RORγt and STAT3 was attenuated in miR-199a-3p oligomer treated UC mice. In conclusion, the data of the study suggest that treatment with miR-199a-3p oligomer ameliorates intestinal barrier in ulcerative colitis by down regulating the IL-17A/IL-23 axis.
溃疡性结肠炎是一种慢性炎症性肠病，死亡率较高。本报告评估了 miR-199a-3p 寡聚物治疗溃疡性结肠炎（UC）的保护作用。通过在小鼠饮用水中给予葡聚糖硫酸钠[DSS（3%）]为期一周诱导溃疡性结肠炎，并对 miR-199a-3p 寡聚物进行相同时间的治疗。通过估计 UC 小鼠的体重、血便和结肠长度来确定 miR-199a-3p 寡聚物的作用。测定 UC 小鼠血清、肠道和脾脏组织中的炎性细胞因子、氧化应激参数和 Treg/Th17 比值。估计 UC 小鼠肠道组织中 TGFβ、Foxp3、RORγt 和 STAT3 的 mRNA 表达。此外，通过估计血清中 FITC-右旋糖酐的表达和 UC 小鼠组织中连接蛋白的表达来确定肠道的通透性。研究数据表明，miR-199a-3p 寡聚物治疗可改善溃疡性结肠炎小鼠的改变情况。miR-199a-3p 寡聚物治疗组肠道中细胞因子和氧化应激参数水平降低。此外，miR-199a-3p 寡聚物治疗的 UC 小鼠肠道通透性增强。血清中 Th17 水平和 TGFβ、Foxp3、RORγt 和 STAT3 的 mRNA 表达在 miR-199a-3p 寡聚物治疗的 UC 小鼠中减弱。总之，该研究的数据表明，miR-199a-3p 寡聚物通过下调 IL-17A/IL-23 轴改善溃疡性结肠炎的肠道屏障。
