Yang Haotian, Zhao Yuan, Chen Yongping, Yang Tianyuan, Dou Xinyi, Li Junfeng, Yang Guiyan, Feng Guofeng, Fang Hao, Fan Honggang, Zhang Shuai
Heilongjiang Key Laboratory for Laboratory Animals and Comparative Medicine, College of Veterinary Medicine, Northeast Agricultural University, Harbin, China.
Heilongjiang Academy of Agricultural Science Branch of Animal Husbandry and Veterinary Branch, Qiqihar, China.
Inflammation. 2025 Feb;48(1):412-425. doi: 10.1007/s10753-024-02065-8. Epub 2024 Jun 19.
This study aimed to investigate the potential protective effects of Dexmedetomidine (DEX) against acute kidney injury (AKI) induced by acute stress (AS). Wistar rats were divided into five groups: Control, DEX, AS, AS + DEX, and AS + A438079. The results showed that AS led to AKI by increasing inflammatory biomarkers and oxidative stress-related indicators. The acute stress model in rats was successfully established. Renal function, histopathology, oxidative stress, and inflammation were assessed. Localization of P2X7 receptor (P2X7R) was determined by immunofluorescence. Additionally, the key inflammatory proteins of the P2X7R/NF-κB/NLRP3 signaling pathway were measured by Western blotting. DEX significantly improved kidney function, alleviated kidney injury, and reduced oxidative stress and inflammation. DEX inhibited the activation of the P2X7R, decreased the expression of NF-κB, NLRP3 inflammasome, and Caspase-1, and inhibited the expression of interleukin-1β (IL-1β) and tumor necrosis factor α (TNFα). Furthermore, DEX also alleviated AS-induced AKI by inhibiting the excessive production of reactive oxygen species (ROS) and reducing oxidative stress. In conclusion, DEX attenuates AS-induced AKI by mitigating inflammation and oxidative stress through the inhibition of the P2X7R/NF-κB/NLRP3 pathway in rats.
本研究旨在探讨右美托咪定（DEX）对急性应激（AS）诱导的急性肾损伤（AKI）的潜在保护作用。将Wistar大鼠分为五组：对照组、DEX组、AS组、AS + DEX组和AS + A438079组。结果显示，AS通过增加炎症生物标志物和氧化应激相关指标导致AKI。成功建立了大鼠急性应激模型。评估了肾功能、组织病理学、氧化应激和炎症。通过免疫荧光法测定P2X7受体（P2X7R）的定位。此外，通过蛋白质免疫印迹法检测P2X7R/NF-κB/NLRP3信号通路的关键炎症蛋白。DEX显著改善了肾功能，减轻了肾损伤，并降低了氧化应激和炎症。DEX抑制了P2X7R的激活，降低了NF-κB、NLRP3炎性小体和半胱天冬酶-1的表达，并抑制了白细胞介素-1β（IL-1β）和肿瘤坏死因子α（TNFα）的表达。此外，DEX还通过抑制活性氧（ROS）的过量产生和降低氧化应激来减轻AS诱导的AKI。总之，DEX通过抑制大鼠P2X7R/NF-κB/NLRP3途径减轻炎症和氧化应激，从而减轻AS诱导的AKI。
