The imidazopyridine derivative X22 prevents diabetic kidney dysfunction through inactivating NF-kappa B signaling
The imidazopyridine derivative X22 prevents diabetic kidney dysfunction through inactivating NF-kappa B signaling
复制标题
咪唑并吡啶衍生物 X22 通过灭活 NF-kappa B 信号传导预防糖尿病肾功能障碍
DOI：
10.1016/j.bbrc.2020.03.016
复制
发表时间：
2020
影响因子：
3.1
通讯作者：
Qian Jianchang
中科院分区：
文献类型：
--
作者：
Jiang Yuchen;Yang Libin;Yang Xiaojing;Yin Sihui;Zhuang Fei;Liu Zhiguo;Wang Yi;Liang Guang;Qian Jianchang
糖尿病肾病（DKD）是一种由高血糖引起的慢性炎症性肾脏疾病。因此，即使对血糖水平进行细致的控制也不能有效地预防DKD的进展。炎症反应的管理可能是最有希望的治疗策略之一。我们先前验证了咪唑并吡啶衍生物（X22）作为抑制脂多糖诱导的炎症的活性化合物。然而，其预防DKD的潜力尚未得到证实。在本研究中，使用链脲佐菌素诱导的1型糖尿病小鼠，通过Q-PCR和免疫印迹法研究X22对DKD相关炎症和纤维化的影响。结果显示，X22能显著抑制炎症细胞因子（IL-6、TNF-α）和纤维化生物标志物的产生。与此同时，肾功能得到了显著改善。为了阐明X22的作用机制，我们研究了其对NRK-52 E细胞系的作用。值得注意的是，X22恢复了IKB-α的蛋白水平，并阻断了P65的核转位。总的来说，数据表明X22可以减轻糖尿病肾功能障碍和炎症损伤，并可能代表治疗DKD的潜在药物。它可能是一种潜在的药物，用于治疗DKD。
Diabetic kidney disease (DKD) is considered a chronic inflammatory renal disease induced by hyperglycemia. Therefore, even meticulous control of blood glucose levels cannot prevent the progression of DKD efficiently. Management of the inflammatory response could be one of the most promising strategies for treatment. We previously validated an imidazopyridine derivative (X22) as an active compound in suppressing lipopolysaccharide-induced inflammation. However, its potential for protection against DKD has not been exanimated. In the present study, streptozotocin-induced type 1 diabetic mice were used to study the effect of X22 on DKD associated inflammation and fibrosis by Q-PCR and immunoblotting assays. The results showed that X22 significantly inhibited the production of inflammatory cytokines (IL-6, TNF-α) and fibrosis biomarkers. At the same time, kidney function was dramatically improved. To elucidate the mechanism of action of X22, we examined its effects on the NRK-52E cell line. Strikingly, X22 restored the protein level of IKB-α and blocked the nuclear translocation of P65. Collectively, the data indicate that X22 can attenuate diabetic kidney dysfunction and inflammatory injury and may represent a potential agent for the treatment of DKD. It could be a potential agent for use in the treatment of DKD.