Dexmedetomidine protects against acute kidney injury through downregulating inflammatory reactions in endotoxemia rats

Tan,Fang; Chen,Yujie; Yuan,Dongdong; Gong,Culian; Li,Xiaoyun; Zhou,Shaoli

doi:10.3892/br.2015.427

Dexmedetomidine protects against acute kidney injury through downregulating inflammatory reactions in endotoxemia rats

Authors:
- Fang Tan
- Yujie Chen
- Dongdong Yuan
- Culian Gong
- Xiaoyun Li
- Shaoli Zhou
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Affiliations: Department of Anesthesiology, The Third Affiliated Hospital of Sun Yat‑sen University, Guangzhou, Guangdong 510630, P.R. China, Department of Intensive Care Unit, Guangzhou Development District Hospital, Guangzhou, Guangdong 510730, P.R. China
Published online on: February 12, 2015 https://doi.org/10.3892/br.2015.427
Pages: 365-370

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Abstract

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 α‑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 µg/kg) 10 min before LPS injection to observe its protective effects. Of note, a unique α‑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 α (TNF‑α) 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‑α were all evidently increased in varying degrees. KIM‑1 and HMGB‑1 expression was upregulated in the LPS group (P<0.05 vs. Sham group). However, when rats were pretreated with DEX, AKI induced by LPS was decreased significantly. Renal pathological injury, plasma Cr, BUN, IL‑6, IL‑18, TNF‑α, and KIM‑1 and HMGB‑1 expression were all reduced (P<0.05 vs. LPS group). In addition, exposure of the α‑2‑adrenergic receptor antagonist, YOH, eliminated this reduction. In conclusion, DEX protected against sepsis‑induced AKI through depressing the inflammatory reaction, mechanisms of which may be associated with α‑2 receptors inhibition.

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