Dexmedetomidine protects against acute kidney injury through downregulating inflammatory reactions in endotoxemia rats
Dexmedetomidine protects against acute kidney injury through downregulating inflammatory reactions in endotoxemia rats
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右美托咪定通过下调内毒素血症大鼠的炎症反应来预防急性肾损伤。
DOI：
10.3892/br.2015.427
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发表时间：
2015-05-01
影响因子：
2.3
通讯作者：
Zhou, Shaoli
中科院分区：
文献类型：
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作者：
Tan, Fang;Chen, Yujie;Zhou, Shaoli
大约42%的脓毒症患者经历了急性肾损伤(AKI)，这明显影响了患者的生存。然而，由于缺乏有效的治疗策略，因此，本研究探讨了高选择性α-2肾上腺素能受体激动剂右美托咪定(DEX)对脓毒症大鼠的保护作用。大鼠尾静脉注射脂多糖(LPS，5 mg/kg)建立脓毒症模型。大鼠在注射脂多糖前10min给予地塞米松(10 mg/kg)，观察其保护作用。值得注意的是，在DEX暴露前30分钟，一种独特的α-2-肾上腺素能受体拮抗剂育亨宾(YOH，1 mg/kg，腹腔注射)也被用来拮抗DEX的保护作用。雄性SD大鼠32只，随机分为假手术组、内毒素组、地塞米松+内毒素组和YOH+地塞米松+内毒素组，每组8只。4h后处死大鼠，观察肾组织的病理变化，包括血肌酐(Cr)、血尿素氮(BUN)、肾损伤分子-1(Kim-1)和高迁移率族蛋白-1(HMGB-1)的表达。检测IL-6、IL-18和肿瘤坏死因子-α(TNF-α)，以探讨内毒素诱导AKI与炎症反应相关的机制。结果表明，内毒素诱导的AKI较为严重。肾组织病理损伤、血浆肌酐、尿素氮、IL-6、IL-18、肿瘤坏死因子-α均有不同程度的升高。内毒素组KIM-1和HMGB-1表达上调(P
Approximately 42% of patients with sepsis undergo acute kidney injury (AKI), which evidently influences patient survival. However, effective therapy strategies are lacking, thus, the present study investigated the protective effects of dexmedetomidine (DEX), a highly selective alpha-2 adrenoceptor agonist, in rat sepsis models. Rat sepsis models were generated through lipopolysaccharide injection (LPS; 5 mg/kg) in the tail vein. Rats were pretreated with DEX (10 mu g/kg) 10 min before LPS injection to observe its protective effects. Of note, a unique alpha-2-adrenergic receptor antagonist, yohimbine (YOH; 1 mg/kg, intraperitoneally), was also used to antagonize the protective effects of DEX 30 min before DEX exposure. Thirty-two male Sprague Dawley rats were randomly divided into the Sham, LPS, DEX + LPS and YOH + DEX + LPS groups (n=8/group). All the rats were sacrificed 4 h later to observe the pathological changes of renal tissue, including plasma creatinine (Cr), blood urea nitrogen (BUN), kidney injury molecule-1 (KIM-1) and high mobility group protein 1 (HMGB-1) expression. Interleukin 6 (IL-6), IL-18 and tumor necrosis factor a (TNF-alpha) were all determined to examine the mechanisms of LPS-induced AKI relative to inflammatory reaction. The results indicated that AKI induced by LPS was serious. Renal pathological injury, plasma Cr, BUN, IL-6, IL-18 and TNF-alpha were all evidently increased in varying degrees. KIM-1 and HMGB-1 expression was upregulated in the LPS group (P