Department of Anesthesiology and Perioperative Medicine, Zhengzhou Central Hospital Affiliated to Zhengzhou University, Zhengzhou 450007, China.
Research of Trauma Center, Zhengzhou Central Hospital Affiliated to Zhengzhou University, Zhengzhou 450007, China.
Cells. 2022 Feb 23;11(5):772. doi: 10.3390/cells11050772.
Inflammatory cells contribute to the pathogenesis of renal ischemia-reperfusion injury (IRI). However, the signaling mechanisms underlying the infiltration of inflammatory cells into the kidney are not well understood. In this study, we examined the effects of phosphoinositide 3 kinase γ (PI3Kγ) on inflammatory cells infiltration into the kidney in response to ischemia-reperfusion injury. Compared with wild-type mice, PI3Kγ knockout mice displayed less IRI in the kidney with fewer tubular apoptotic cell. Furthermore, PI3Kγ deficiency decreased the number of infiltrated neutrophils, macrophages, and T cells in the kidney, which was accompanied by a decrease in the expression of pro-inflammatory cytokines in the kidney. Moreover, wild-type mice treated with AS-605240, a selective PI3Kγ inhibitor, displayed less tubular damage, accumulated fewer inflammatory cells, and expressed less proinflammatory molecules in the kidney following IRI. These results demonstrate that PI3Kγ has a critical role in the pathogenesis of kidney damage in IRI, indicating that PI3Kγ inhibition may serve as a potential therapeutic strategy for the prevention of ischemia-reperfusion-induced kidney injury.
炎症细胞有助于肾缺血再灌注损伤（IRI）的发病机制。然而，炎症细胞浸润肾脏的信号机制尚不清楚。在这项研究中，我们研究了磷酸肌醇 3 激酶γ（PI3Kγ）在缺血再灌注损伤时对炎症细胞浸润肾脏的影响。与野生型小鼠相比，PI3Kγ 基因敲除小鼠的肾脏 IRI 减轻，肾小管凋亡细胞减少。此外，PI3Kγ 缺乏导致肾脏浸润的中性粒细胞、巨噬细胞和 T 细胞数量减少，同时肾脏中促炎细胞因子的表达减少。此外，用 PI3Kγ 选择性抑制剂 AS-605240 处理的野生型小鼠，在 IRI 后肾脏的小管损伤减轻，炎症细胞积聚减少，促炎分子的表达减少。这些结果表明 PI3Kγ 在 IRI 中肾脏损伤的发病机制中起关键作用，表明 PI3Kγ 抑制可能是预防缺血再灌注诱导的肾损伤的一种潜在治疗策略。
