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Abstract：
UNASSIGNED: This study explored the molecular mechanisms by which dexmedetomidine (Dex) alleviates cisplatin (CP)-induced acute kidney injury (AKI) in rats.
UNASSIGNED: CP-induced AKI models were established, and Dex was intraperitoneally injected at different concentrations into rats in the model groups. Subsequently, rats were assigned to the control, CP, CP + Dex 10 μg/kg, and CP + Dex 25 μg/kg groups. After weighing the kidneys of the rats, the kidney arterial resistive index was calculated, and CP-induced AKI was evaluated. In addition, four serum biochemical indices were measured: histopathological damage in rat kidneys was detected; levels of inflammatory factors, interleukin (IL)-1β, IL-18, IL-6, and tumor necrosis factor alpha, in kidney tissue homogenate of rats were assessed through enzyme-linked immunosorbent assay (ELISA); and levels of NLRP-3, caspase-1, cleaved caspase-1, gasdermin D (GSDMD), and GSDMD-N in kidney tissues of rats were determined via western blotting.
UNASSIGNED: Dex treatment reduced nephromegaly and serum clinical marker upregulation caused by CP-induced AKI. In addition, hematoxylin and eosin staining revealed that Dex treatment relieved CP-induced kidney tissue injury in AKI rats. ELISA analyses demonstrated that Dex treatment reduced the upregulated levels of proinflammatory cytokines in the kidney tissue of AKI rats induced by CP, thereby alleviating kidney tissue injury. Western blotting indicated that Dex alleviated CP-induced AKI by inhibiting pyroptosis mediated by NLRP-3 and caspase-1.
UNASSIGNED: Dex protected rats from CP-induced AKI, and the mechanism may be related to NLRP-3/Caspase-1-mediated pyroptosis.
UNASSIGNED: CP-induced AKI models were established, and Dex was intraperitoneally injected at different concentrations into rats in the model groups. Subsequently, rats were assigned to the control, CP, CP + Dex 10 μg/kg, and CP + Dex 25 μg/kg groups. After weighing the kidneys of the rats, the kidney arterial resistive index was calculated, and CP-induced AKI was evaluated. In addition, four serum biochemical indices were measured: histopathological damage in rat kidneys was detected; levels of inflammatory factors, interleukin (IL)-1β, IL-18, IL-6, and tumor necrosis factor alpha, in kidney tissue homogenate of rats were assessed through enzyme-linked immunosorbent assay (ELISA); and levels of NLRP-3, caspase-1, cleaved caspase-1, gasdermin D (GSDMD), and GSDMD-N in kidney tissues of rats were determined via western blotting.
UNASSIGNED: Dex treatment reduced nephromegaly and serum clinical marker upregulation caused by CP-induced AKI. In addition, hematoxylin and eosin staining revealed that Dex treatment relieved CP-induced kidney tissue injury in AKI rats. ELISA analyses demonstrated that Dex treatment reduced the upregulated levels of proinflammatory cytokines in the kidney tissue of AKI rats induced by CP, thereby alleviating kidney tissue injury. Western blotting indicated that Dex alleviated CP-induced AKI by inhibiting pyroptosis mediated by NLRP-3 and caspase-1.
UNASSIGNED: Dex protected rats from CP-induced AKI, and the mechanism may be related to NLRP-3/Caspase-1-mediated pyroptosis.
摘要：
■本研究探索右美托咪定(Dex)减轻顺铂(CP)诱导的大鼠急性肾损伤(AKI)的分子机制。
■建立CP诱导的AKI模型，模型组大鼠腹腔注射不同浓度的Dex。随后，大鼠被分配到对照组，CP,CP+Dex10μg/kg，和CP+Dex25μg/kg组。称重大鼠的肾脏后，计算了肾动脉阻力指数，并对CP诱导的AKI进行评价。此外,检测4项血清生化指标:检测大鼠肾脏组织病理学损伤;白细胞介素（IL）-1β，IL-18、IL-6和肿瘤坏死因子α，通过酶联免疫吸附试验（ELISA）评估大鼠肾组织匀浆中的NLRP-3，caspase-1，cleavedcaspase-1，gasderminD（GSDMD）的水平，通过蛋白质印迹法测定大鼠肾组织中的GSDMD-N。
■Dex治疗可减少CP诱导的AKI引起的肾肥大和血清临床标志物上调。此外,苏木精和伊红染色显示Dex治疗减轻了CP诱导的AKI大鼠肾组织损伤。ELISA分析表明，Dex治疗降低了CP诱导的AKI大鼠肾组织中促炎细胞因子的上调水平，从而减轻肾组织损伤。Western印迹表明Dex通过抑制NLRP-3和caspase-1介导的焦亡减轻CP诱导的AKI。
■Dex保护大鼠免受CP诱导的AKI，其机制可能与NLRP-3/Caspase-1介导的细胞凋亡有关。
■建立CP诱导的AKI模型，模型组大鼠腹腔注射不同浓度的Dex。随后，大鼠被分配到对照组，CP,CP+Dex10μg/kg，和CP+Dex25μg/kg组。称重大鼠的肾脏后，计算了肾动脉阻力指数，并对CP诱导的AKI进行评价。此外,检测4项血清生化指标:检测大鼠肾脏组织病理学损伤;白细胞介素（IL）-1β，IL-18、IL-6和肿瘤坏死因子α，通过酶联免疫吸附试验（ELISA）评估大鼠肾组织匀浆中的NLRP-3，caspase-1，cleavedcaspase-1，gasderminD（GSDMD）的水平，通过蛋白质印迹法测定大鼠肾组织中的GSDMD-N。
■Dex治疗可减少CP诱导的AKI引起的肾肥大和血清临床标志物上调。此外,苏木精和伊红染色显示Dex治疗减轻了CP诱导的AKI大鼠肾组织损伤。ELISA分析表明，Dex治疗降低了CP诱导的AKI大鼠肾组织中促炎细胞因子的上调水平，从而减轻肾组织损伤。Western印迹表明Dex通过抑制NLRP-3和caspase-1介导的焦亡减轻CP诱导的AKI。
■Dex保护大鼠免受CP诱导的AKI，其机制可能与NLRP-3/Caspase-1介导的细胞凋亡有关。
