Division of Nephrology, Department of Internal Medicine, Kyung Hee University Hospital at Gangdong, Seoul 05278, Korea.
Department of Core Research Laboratory, Medical Science Institute, Kyung Hee University Hospital at Gangdong, Seoul 05278, Korea.
Int J Mol Sci. 2021 Feb 5;22(4):1627. doi: 10.3390/ijms22041627.
Renal ischemia-reperfusion injury (IRI) is involved in the majority of clinical conditions that manifest as renal function deterioration; however, specific treatment for this type of injury is still far from clinical use. Since Toll-like receptor (TLR)-mediated signaling is a key mediator of IRI, we examined the effect of a multiple-TLR-blocking peptide named TLR-inhibitory peptide 1 (TIP1), which exerts the strongest action on TLR4, on renal IRI. We subjected C57BL/6 mice to 23 min of renal pedicle clamping preceded by intraperitoneal injection with a vehicle or TIP1. Sham control mice underwent flank incision only. Mouse kidneys were harvested after 24 h of reperfusion for histology, western blot, RT-PCR, and flow cytometry analysis. Pretreatment with TIP1 lowered the magnitude of elevated plasma creatinine levels and attenuated tubular injury. TIP1 treatment also reduced mRNA expression of inflammatory cytokines and decreased apoptotic cells and oxidative stress in post-ischemic kidneys. In kidneys pretreated with TIP1, the infiltration of macrophages and T helper 17 cells was less abundant than those in the IRI only group. These results suggest that TIP1 has a potential beneficial effect in attenuating the degree of kidney damage induced by IRI.
肾缺血再灌注损伤（IRI）与大多数表现为肾功能恶化的临床病症有关；然而，针对这种损伤的特定治疗方法仍远未应用于临床。由于 Toll 样受体（TLR）介导的信号转导是 IRI 的关键介质，我们研究了一种名为 TLR 抑制肽 1（TIP1）的多 TLR 阻断肽对肾 IRI 的影响，该肽对 TLR4 具有最强的作用。我们使 C57BL/6 小鼠经历 23 分钟的肾蒂夹闭，此前通过腹腔内注射载体或 TIP1 进行预处理。假手术对照小鼠仅接受侧腹切口。再灌注 24 小时后采集小鼠肾脏进行组织学、western blot、RT-PCR 和流式细胞术分析。TIP1 预处理降低了升高的血浆肌酐水平的幅度，并减轻了肾小管损伤。TIP1 治疗还降低了缺血后肾脏中炎症细胞因子的 mRNA 表达，并减少了凋亡细胞和氧化应激。在 TIP1 预处理的肾脏中，巨噬细胞和辅助性 T 细胞 17 细胞的浸润比仅 IRI 组少。这些结果表明，TIP1 具有减轻 IRI 引起的肾脏损伤程度的潜在有益作用。
