Department of Anesthesiology, Suzhou Kowloon Hospital, Shanghai Jiaotong University School of Medicine, Suzhou 215028 , China.
Department of Thoracic Surgery, Wuzhong People's Hospital, Suzhou 215028 , China.
Cell Mol Biol (Noisy-le-grand). 2020 May 15;66(2):93-98.
The current research aimed to study the effects of dexmedetomidine (DEX) pretreatment on rats with sepsis-induced acute kidney injury (SAKI) and miR-146a expression. The model of SAKI was established through the tail vein injection of lipopolysaccharide (LSP). We used an automatic biochemical analyzer to detect serum urea nitrogen (BUN) and creatinine (Cre) levels. The expression levels of urine KIM-1 and NGAL and serum IL-1β and IL-6 were analyzed by enzyme-linked immunosorbent assay (ELISA). The content and activity of superoxide dismutase (SOD) were detected by the xanthine oxidase method. The content of malondialdehyde (MDA) was determined by the thiobarbituric acid (TBA) method. Reactive oxygen species (ROS) was detected by fluorescent probe DCFH-DA. Catalase (CAT) was detected by potassium permanganate titration. The expression level of miR-146a in the renal tissue and serum was detected by RT-PCR. The expression levels of Nrf2 and HO-1 proteins were detected by Western blot. Compared with those in the model group, rats in the DEX group had significantly lower expression levels of serum BUN, Cre, IL-1β, and IL-6, and oxidant markers MDA and ROS, but significantly higher expression levels of miR-146a and antioxidant markers SOD and CAT. DEX pretreatment could improve the kidney morphology, injury severity, and Nrf2 and HO-1 proteins of rats with SAKI. In conclusion, DEX can improve oxidative stress and inflammatory responses in rats with SAKI, reduce the severity of the renal injury, and up-regulate the expression level of miR-146a.
本研究旨在探讨右美托咪定（DEX）预处理对脂多糖（LPS）尾静脉注射诱导的脓毒症急性肾损伤（SAKI）大鼠及 miR-146a 表达的影响。采用 LPS 尾静脉注射建立 SAKI 模型。采用全自动生化分析仪检测血清尿素氮（BUN）和肌酐（Cre）水平。酶联免疫吸附试验（ELISA）检测尿 KIM-1 和 NGAL 及血清 IL-1β和 IL-6 的表达水平。黄嘌呤氧化酶法检测超氧化物歧化酶（SOD）的含量和活性。硫代巴比妥酸（TBA）法检测丙二醛（MDA）含量。荧光探针 DCFH-DA 检测活性氧（ROS）。过锰酸钾滴定法检测过氧化氢酶（CAT）。RT-PCR 检测肾组织和血清中 miR-146a 的表达水平。Western blot 检测 Nrf2 和 HO-1 蛋白的表达水平。与模型组相比，DEX 组大鼠血清 BUN、Cre、IL-1β和 IL-6 及氧化应激标志物 MDA 和 ROS 表达水平明显降低，miR-146a 及抗氧化应激标志物 SOD 和 CAT 表达水平明显升高。DEX 预处理可改善 SAKI 大鼠的肾脏形态、损伤程度及 Nrf2 和 HO-1 蛋白表达。综上所述，DEX 可改善 SAKI 大鼠氧化应激和炎症反应，减轻肾损伤程度，上调 miR-146a 的表达水平。
