白细胞介素-6 受体阻断通过抑制炎症小体改善糖尿病肾病。
IL-6 receptor blockade ameliorates diabetic nephropathy via inhibiting inflammasome in mice.
机构信息
Department of Nephrology, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai 200233, China.
Department of Nephrology, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Jiangsu University Affiliated Shanghai Eighth People's Hospital, Shanghai 200233, China.
出版信息
Metabolism. 2018 Jun;83:18-24. doi: 10.1016/j.metabol.2018.01.002. Epub 2018 Jan 12.
BACKGROUND AND OBJECTIVE
Interleukin 6 (IL-6) has been identified as a key mediator in inflammation, immune responses and glucose metabolism. In this study, we assessed the effects of an IL-6 receptor antibody on diabetic nephropathy in a mouse model of type 2 diabetes mellitus.
METHODS
Twelve week old male db/db mice were treated with Tocilizumab (an IL-6 receptor antibody), normal IgG1 control antibody, insulin or normal saline for 12 weeks. Renal injury, inflammation and insulin resistance were assessed.
RESULTS
Db/db mice treated with Tocilizumab exhibited reduced proteinuria and glomerular mesangial matrix accumulation compared to db/db + IgG controls. Additionally, Tocilizumab suppressed inflammatory response, oxidative stress and the IL-6 signaling pathway in the diabetic kidneys. It is noteworthy that blockade of IL-6 receptor blunted the activation of NLRP3 inflammasome partly through inhibition of IL-17A. Furthermore, insulin resistance assessed by glucose tolerance test, was ameliorated by Tocilizumab treatment.
CONCLUSIONS
The protective effects of an IL-6 receptor blockade against diabetic renal injury may be due to decreased insulin resistance and inhibition of the inflammasome.
背景与目的
白细胞介素 6（IL-6）已被确定为炎症、免疫反应和葡萄糖代谢中的关键介质。在本研究中，我们评估了 IL-6 受体抗体在 2 型糖尿病小鼠模型中对糖尿病肾病的作用。
方法
12 周龄雄性 db/db 小鼠接受托珠单抗（一种 IL-6 受体抗体）、正常 IgG1 对照抗体、胰岛素或生理盐水治疗 12 周。评估肾脏损伤、炎症和胰岛素抵抗。
结果
与 db/db+IgG 对照组相比，接受托珠单抗治疗的 db/db 小鼠蛋白尿和肾小球系膜基质积聚减少。此外，托珠单抗抑制了糖尿病肾脏中的炎症反应、氧化应激和 IL-6 信号通路。值得注意的是，阻断 IL-6 受体部分通过抑制白介素 17A 使 NLRP3 炎性小体的激活减弱。此外，托珠单抗治疗改善了葡萄糖耐量试验评估的胰岛素抵抗。
结论
IL-6 受体阻断对糖尿病肾脏损伤的保护作用可能是由于胰岛素抵抗降低和炎性小体抑制。
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