Dexmedetomidine protects against renal ischemia and reperfusion injury by inhibiting the JAK/STAT signaling activation

Journal of Translational Medicine

Daqing Ma²  Akbar Vohra¹  Xiaobing Yang³  Jinsong Wang³  Chenhui Liu⁴  Li Xu⁴  Yuan Zhang⁴  Hongwei Shi⁴  Liu Han⁴  Hongguang Bao⁴  Yanna Si⁴ 

[1] Manchester Academic Health Sciences Centre, Manchester Royal Infirmary, Manchester M13 9WL, UK;Anaesthetics, Pain Medicine and Intensive Care, Department of Surgery and Cancer, Faculty of Medicine, Imperial College London, Chelsea Westminster Campus, 369 Fulham Rd, London Sw10 9NH, UK;Department of Pathology, Nanjing First Hospital, Nanjing Medical University, Nanjing 210006, People’s Republic of China;Department of Anesthesiology, Nanjing First Hospital, Nanjing Medical University, Nanjing 210006, People’s Republic of China

关键词: Renoprotection;    JAK/STAT;    AG490;    Ischemia and Reperfusion Injury;    Dexmedetomidine;   

Others  :  827451
DOI  :  10.1186/1479-5876-11-141

 received in 2013-03-10, accepted in 2013-05-22,  发布年份 2013

【 摘 要 】

Background

The α₂-adrenoreceptor agonist dexmedetomidine is known to provide renoprotection against ischemia and reperfusion (I/R) injury. However the underlying molecular mechanisms remain unclear. The purpose of this study was to investigate whether the Janus kinase and signal transducer and activator of transcription (JAK/STAT) signaling pathway plays a role in dexmedetomidine’s renoprotection.

Methods

I/R model was induced by bilateral renal pedicle clamping for 45 min followed by 48 h of reperfusion in male Wistar rat. Sham laparotomy served as controls. Animals received dexmedetomidine (50 μg/kg, i.p.) in the absence or presence of atipamezole (250 μg/kg, i.p.), or vehicle (DMSO) in the absence or presence of selective JAK2 inhibitor tyrphostin AG490 (10 mg/kg, i.p.) before ischemia. Renal function, histology, apoptosis, expression of cleaved caspase 3 protein, intercellular adhesion molecule-1 (ICAM-1), monocyte chemoattractant protein-1 (MCP-1) and phosphorylations of JAK2, STAT1 and STAT3 were assessed.

Results

The animals treated with either dexmedetomidine or AG490 exhibited an improved renal functional recovery, attenuated histological lesions and reduced number of apoptotic tubular epithelial cells. Either dexmedetomidine or AG490 inhibited the phosphorylations of JAK2 and its downstream molecule STAT1 and STAT3, accompanied by down-regulation the expression of cleaved caspase 3, ICAM-1 and MCP-1 proteins, and significantly ameliorated renal I/R injury.

Conclusions

Dexmedetomidine protects kidney against I/R injury, at least in part, through its inhibitory effects on injury-induced activation of JAK/STAT signaling pathway. If our data can be extrapolated to clinical setting, then dexmedetomidine may therefore serve as a clinical strategy to treat/prevent perioperative renal I/R injury.

【 授权许可】

   
2013 Si et al.; licensee BioMed Central Ltd.

【 图 表 】

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