Shi Chongxu, Zhao Danyang, Lyubenov Lyuben, Motrapu Manga, Li Na, Steiger Stefanie, Mammadova-Bach Elmina, Yang Luying, Liu Dong, Anders Hans-Joachim
Nantong Laboratory of Development and Diseases, School of Life Sciences, Medical College, Nantong University, Nantong, China.
Renal Division, Medizinische Klinik und Poliklinik IV, Klinikum der Universität München, Ludwig-Maximilians University Munich, Munich, Germany.
Front Cardiovasc Med. 2022 Jul 28;9:974759. doi: 10.3389/fcvm.2022.974759. eCollection 2022.
Cholesterol crystal (CC) embolism can cause acute tissue infarction and ischemic necrosis via triggering diffuse thrombotic angiopathy occluding arterioles and arteries. Neutrophils contribute to crystal-induced immunothrombosis as well as to ischemic necrosis-related necroinflammation. We speculated that CC embolism-induced acute kidney injury (AKI) would be circadian rhythm-dependent and associated with cyclic differences in neutrophil function. Injection of CC into the left kidney induced thrombotic angiopathy progressing starting as early as 3 h after CC injection followed by a progressive ischemic cortical necrosis and AKI at 24 h. In C57BL/6J mice, circulating CD11bLy6G neutrophils were higher during the day phase [Zeitgeber time (ZT) 0-12] compared to the dark phase (ZT12-24). In the time frame of thrombus formation at ZT13, more neutrophils were recruited into the injured kidney 24 h later compared to CC embolism at ZT5. This effect was associated with an increased circulating number of CXCR2 neutrophils as well as an upregulated kidney adhesion molecule and chemokine expression. These findings were associated with a significant increase in kidney necrosis, and endothelial injury at ZT13. Thus, the time of day has an effect also on CC embolism-related AKI in association with the circadian rhythm of neutrophil recruitment.
胆固醇结晶（CC）栓塞可通过引发弥漫性血栓性血管病，阻塞小动脉和动脉，从而导致急性组织梗死和缺血性坏死。中性粒细胞在晶体诱导的免疫血栓形成以及与缺血性坏死相关的坏死性炎症中发挥作用。我们推测，CC栓塞诱导的急性肾损伤（AKI）具有昼夜节律依赖性，并与中性粒细胞功能的周期性差异有关。将CC注入左肾会引发血栓性血管病，最早在注入CC后3小时开始进展，随后在24小时出现进行性缺血性皮质坏死和AKI。在C57BL/6J小鼠中，与黑夜阶段（ Zeitgeber时间[ZT]12 - 24）相比，白天阶段（ZT0 - 12）循环中的CD11bLy6G中性粒细胞数量更高。在ZT13形成血栓的时间范围内，与ZT5时的CC栓塞相比，24小时后更多的中性粒细胞被募集到受损肾脏中。这种效应与循环中CXCR2中性粒细胞数量增加以及肾脏黏附分子和趋化因子表达上调有关。这些发现与ZT13时肾脏坏死和内皮损伤的显著增加有关。因此，一天中的时间也会对与CC栓塞相关的AKI产生影响，这与中性粒细胞募集的昼夜节律有关。
