Dong Youdan, Zhang Zeming, Liu Hezuo, Jia Lihong, Qin Muting, Wang Xiaofei
Department of Rheumatology, Shengjing Hospital of China Medical University Shenyang 110022, Liaoning Province, China.
Department of Child and Adolescent Health, School of Public Health, China Medical University Shenyang 110122, Liaoning Province, China.
Am J Transl Res. 2020 Feb 15;12(2):649-659. eCollection 2020.
For the development of Lupus nephritis, environmental factors are reasoned to be one of the risk factors. In recent years, the role of bisphenol A (BPA) in kidney injury has attracted wide attention. In this study, we explored the nephrotoxicity and its possible mechanism of BPA exposure to lupus-prone MRL/lpr mice. Orally exposure of BPA increased serum anti-dsDNA level and urinary protein, and aggravated renal pathological injury in MRL/lpr mice. BPA increased the expression of NF-κB protein and activated the inflammatory response in both MRL/lpr and C57 mice. Unlike C57 mice, BPA exposure partially activated autophagy associated proteins, but the autophagy signaling pathway lacked the regulation of Becline1 and LC3-associated phagocytosis deficiency, and decreased Nrf2 protein expression in renal tissue of MRL/lpr mice. Therefore, exacerbating lupus nephritis induced by BPA exposure was associated with the activation of inflammation, abnormal autophagy and decreased antioxidant ability.
对于狼疮性肾炎的发展，环境因素被认为是危险因素之一。近年来，双酚A（BPA）在肾脏损伤中的作用引起了广泛关注。在本研究中，我们探讨了BPA暴露于易患狼疮的MRL/lpr小鼠的肾毒性及其可能机制。口服BPA可增加MRL/lpr小鼠血清抗双链DNA水平和尿蛋白，并加重肾脏病理损伤。BPA增加了NF-κB蛋白的表达，并激活了MRL/lpr和C57小鼠的炎症反应。与C57小鼠不同，BPA暴露部分激活了自噬相关蛋白，但自噬信号通路缺乏Becline1的调节和LC3相关吞噬缺陷，且降低了MRL/lpr小鼠肾组织中Nrf2蛋白的表达。因此，BPA暴露诱导的狼疮性肾炎加重与炎症激活、自噬异常和抗氧化能力下降有关。
