Pang Ran, Dong Lei, Liu Jingfeng, Ji Xiaojun, Zhuang Haizhou, Duan Meili
Department of Critical Care Medicine, Beijing Friendship Hospital, Capital Medical University, Beijing, China.
Heliyon. 2023 Feb 14;9(3):e13796. doi: 10.1016/j.heliyon.2023.e13796. eCollection 2023 Mar.
Sepsis often causes acute kidney injury (AKI). Autophagy of renal tubular epithelial cells is considered a cytoprotective mechanism in septic AKI; however, the role of autophagy of renal endothelial cells is uninvestigated. The current study examined whether autophagy was induced by sepsis in renal endothelial cells and whether induction of autophagy in these cells attenuated the degree of AKI. Cecal ligation and puncture (CLP) was used as a model of sepsis in rats. Four experimental groups included: sham, CLP alone, CLP + rapamycin (RAPA), and CLP + dimethyl sulfoxide (DMSO), where RAPA was used as an activator of autophagy. CLP increased renal LC3-II protein levels with an additional transient increase by RAPA at 18 h. In addition, CLP induced autophagosome formation in renal endothelial cells had an additional increase induced by RAPA. Interestingly, the levels of bone morphogenetic protein and activin membrane-bound inhibitor (BAMBI), an endothelial cell-specific protein in the kidney, were also increased by CLP, albeit it was transiently downregulated by RAPA at 18 h. Serum thrombomodulin increased and renal vascular endothelial (VE)-cadherin decreased following CLP, and these changes were attenuated by RAPA. The renal cortex exhibited and inflammatory tissue damage after CLP, and RAPA alleviated these histopathological injuries. The current findings indicate that autophagy was induced by sepsis in renal endothelial cells, and upregulation of autophagy in these cells alleviated endothelial injury and AKI. In addition, BAMBI was induced by sepsis in the kidney, which may play a role in regulating endothelial stability in septic AKI.
脓毒症常导致急性肾损伤（AKI）。肾小管上皮细胞自噬被认为是脓毒症诱导的急性肾损伤中的一种细胞保护机制；然而，肾内皮细胞自噬的作用尚未得到研究。本研究探讨脓毒症是否能诱导肾内皮细胞自噬，以及诱导这些细胞自噬是否能减轻急性肾损伤的程度。采用盲肠结扎穿孔术（CLP）建立大鼠脓毒症模型。四个实验组包括：假手术组、单纯CLP组、CLP + 雷帕霉素（RAPA）组和CLP + 二甲基亚砜（DMSO）组，其中RAPA用作自噬激活剂。CLP使肾LC3-II蛋白水平升高，RAPA在18小时时使其额外短暂升高。此外，CLP诱导肾内皮细胞自噬体形成，RAPA使其进一步增加。有趣的是，骨形态发生蛋白和激活素膜结合抑制剂（BAMBI）（一种肾脏中的内皮细胞特异性蛋白）的水平也因CLP而升高，尽管RAPA在18小时时使其短暂下调。CLP后血清血栓调节蛋白升高，肾血管内皮（VE）-钙黏蛋白降低，而RAPA减轻了这些变化。CLP后肾皮质出现炎症组织损伤，RAPA减轻了这些组织病理学损伤。目前的研究结果表明，脓毒症可诱导肾内皮细胞自噬，这些细胞自噬的上调减轻了内皮损伤和急性肾损伤。此外，脓毒症可诱导肾脏中的BAMBI表达，这可能在脓毒症诱导的急性肾损伤中调节内皮稳定性方面发挥作用。
