Yu Cheng, Gao Cui-Min, Xie Na, Wang Xiao-Qing, Ma Yu-Qing
Department of Anesthesiology, First Hospital of Lanzhou University, Lanzhou, Gansu 730000, P.R. China.
Exp Ther Med. 2021 May;21(5):475. doi: 10.3892/etm.2021.9906. Epub 2021 Mar 12.
The aim of the present study was to determine whether the effects and underlying mechanisms of ticagrelor in a rat model of sepsis-induced acute kidney injury (AKI) were mediated via the CD62P pathway. A total of 15 rats were randomly assigned to the following groups: Normal, sham, cecal ligation and puncture (CLP), CLP + clinical dose of ticagrelor (CCD) and CLP + loading dose of ticagrelor (CLD). Ticagrelor was administered 12 h before modeling, immediately after modeling, and 12 h after modeling at a dose of 8.6 and 46.42 mg/kg in the CCD and CLD groups, respectively. Rats in the normal, sham and CLP groups were treated with the same volume of distilled water. Serum creatinine (SCr), CD62P and interleukin-1β (IL-1β) levels, myeloperoxidase (MPO) activity in the renal tissue and the apoptosis rate of renal cells were increased in the CLP group, compared with in the normal and sham groups (P<0.05). In addition, ticagrelor treatment reduced SCr, CD62P and IL-1β expression levels, renal tissue MPO activity and renal cell apoptosis in rats with sepsis-induced AKI (P<0.05). CD62P expression was closely associated with the occurrence of sepsis-induced AKI. The mechanism of ticagrelor-mediated reductions in inflammation, renal neutrophil infiltration and renal cell apoptosis is possibly associated with reductions in CD62P expression.
本研究的目的是确定替格瑞洛在脓毒症诱导的急性肾损伤（AKI）大鼠模型中的作用及其潜在机制是否通过CD62P途径介导。总共15只大鼠被随机分为以下几组：正常组、假手术组、盲肠结扎穿孔（CLP）组、CLP + 替格瑞洛临床剂量组（CCD）和CLP + 替格瑞洛负荷剂量组（CLD）。在建模前12小时、建模后立即以及建模后12小时分别给予替格瑞洛，CCD组和CLD组的剂量分别为8.6和46.42 mg/kg。正常组、假手术组和CLP组的大鼠用相同体积的蒸馏水治疗。与正常组和假手术组相比，CLP组血清肌酐（SCr）、CD62P和白细胞介素-1β（IL-1β）水平、肾组织髓过氧化物酶（MPO）活性以及肾细胞凋亡率均升高（P<0.05）。此外，替格瑞洛治疗降低了脓毒症诱导的AKI大鼠的SCr、CD62P和IL-1β表达水平、肾组织MPO活性以及肾细胞凋亡（P<0.05）。CD62P表达与脓毒症诱导的AKI的发生密切相关。替格瑞洛介导的炎症、肾中性粒细胞浸润和肾细胞凋亡减少的机制可能与CD62P表达降低有关。
