The ameliorative effects of α7 nicotinic acetylcholine receptor (α7nAChR) agonists have been demonstrated in acute kidney injury (AKI) caused by multiple stimulations. However, the ameliorative effect of α7nAChR on sepsis-induced acute kidney injury (SAKI) in the cecal ligation and puncture (CLP) model is unclear. Previous studies have demonstrated that α7nAChR is highly expressed on the surface of CD4+CD25+ regulatory T cells (Tregs). However, the role of Tregs in SAKI is unclear. We hypothesized that Tregs might play a role in the ameliorative effect of α7nAChR on SAKI. Hence, in this study, we determined the effects of PNU-282987 (a selective α7nAchR agonist) on SAKI and evaluated whether PNU-282987 would attenuate SAKI via regulating Tregs. Our study showed that immediate administration of PNU-282987 after CLP surgery in rats improved renal function, reduced levels of systemic inflammatory factors (tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), etc.), inflammatory cell infiltration and tubular apoptosis in renal tissues, and increased forkhead/winged helix transcription factor p3 (Foxp3) and cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) expression indicating activated Tregs. Moreover, in in vitro experiments, isolated Tregs co-cultured with PNU-282987 also displayed enhanced expression of CTLA-4 and Foxp3. Furthermore, Tregs were co-cultured with PNU-282987 for 24 hours and then reinfused into rats through the tail vein immediately after CLP surgery, and a significant renal protective effect was observed 24 hours postoperatively. These results demonstrate that PNU-282987 exerts its renal protective effects on SAKI through activation of Tregs.

中文翻译：

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α7nAChR 激动剂 PNU-282987 通过大鼠中的 CD4+CD25+ 调节性 T 细胞改善败血症引起的急性肾损伤。

α7 烟碱型乙酰胆碱受体 (α7nAChR) 激动剂的改善作用已在多重刺激引起的急性肾损伤 (AKI) 中得到证实。然而，α7nAChR 对盲肠结扎穿孔 (CLP) 模型中败血症诱导的急性肾损伤 (SAKI) 的改善作用尚不清楚。先前的研究表明，α7nAChR 在 CD4+CD25+ 调节性 T 细胞 (Tregs) 的表面高表达。然而，Tregs 在 SAKI 中的作用尚不清楚。我们假设 Tregs 可能在 α7nAChR 对 SAKI 的改善作用中发挥作用。因此，在本研究中，我们确定了 PNU-282987（一种选择性 α7nAchR 激动剂）对 SAKI 的影响，并评估了 PNU-282987 是否会通过调节 Treg 来减轻 SAKI。我们的研究表明，在大鼠 CLP 手术后立即给予 PNU-282987 可改善肾功能，降低全身炎症因子（肿瘤坏死因子-α (TNF-α)、白介素-6 (IL-6) 等）的水平，肾组织中的炎症细胞浸润和肾小管细胞凋亡，叉头/翼状螺旋转录因子 p3 (Foxp3) 和细胞毒性 T 淋巴细胞相关蛋白 4 (CTLA-4) 表达增加，表明 Treg 激活。此外，在体外实验中，与 PNU-282987 共培养的分离 Tregs 也表现出增强的 CTLA-4 和 Foxp3 表达。此外，Tregs 与 PNU-282987 共培养 24 小时，然后在 CLP 手术后立即通过尾静脉回输给大鼠，术后 24 小时观察到显着的肾脏保护作用。