右美托咪定预处理发挥神经保护作用，抑制 TLR4/NF-κB 通路脑缺血再灌注模型。
Dexmedetomidine preconditioning plays a neuroprotective role and suppresses TLR4/NF-κB pathways model of cerebral ischemia reperfusion.
机构信息
Shandong Provincial Hospital, Shandong University, Jinan, Shandong Province, China.
Qianfoshan Hospital Affiliated to Shandong University, Jinan, Shandong Province, China.
出版信息
Biomed Pharmacother. 2017 Sep;93:1337-1342. doi: 10.1016/j.biopha.2017.06.051. Epub 2017 Jul 24.
BACKGROUND
Dexmedetomidine has been reported to play an efficient role on multi-organ protection. Our study aims to investigate the neuroprotective of dexmedetomidine preconditioning on cerebral ischemic reperfusion (I/R) injury and investigate the underlining signaling mechanisms.
METHODS
Cerebral I/R models were established with SD rats through middle cerebral artery occlusion (MCAO). After 2h of ischemia followed by 7days of reperfusion, the degree of cerebral tissue injury was detected by HE, Nissl and TUNEL staining. Glial fibrillary acidic protein (GFAP) positive and TNF-α positive cells were stained by immunohistochemistry and counted under microscope. TLR4, NF-κB and TIR-domain containing adapter-inducing interferon-β (TRIF) expression were detected by real time PCR and western blot.
RESULTS
Dexmedetomidine preconditioning markedly prevented the ischemia-induced cellular damage observed from HE and Nissl staining in hippocampus and cortex. Dexmedetomidine observably decreased the number of apoptotic cells in TUNEL staining. Besides, yohimbine could specifically suppress the protective effect of dexmedetomidine. GFAP expression was distinctly inhibited by dexmedetomidine preconditioning (10μg/kg, 20μg/kg) in cerebral ischemia area. Dexmedetomidine preconditioning inhibited the expression of TLR4 and NF-κB and increased that of TRIF.
CONCLUSION
The results of this study suggest that dexmedetomidine preconditioning plays a neuroprotective role against I/R injury. Dexmedetomidine might suppress TLR4/NF-??B pathway and drive TLR4/TRIF signaling pathway to reduce the inflammatory injury.
背景
右美托咪定已被报道在多器官保护方面发挥有效作用。我们的研究旨在探讨右美托咪定预处理对脑缺血再灌注（I/R）损伤的神经保护作用，并探讨其潜在的信号机制。
方法
通过大脑中动脉闭塞（MCAO）建立 SD 大鼠脑 I/R 模型。缺血 2h 后再灌注 7d，采用 HE、尼氏和 TUNEL 染色检测脑组织损伤程度。免疫组织化学染色和显微镜下计数观察胶质纤维酸性蛋白（GFAP）阳性和肿瘤坏死因子-α（TNF-α）阳性细胞。采用实时 PCR 和 Western blot 检测 TLR4、NF-κB 和 TIR 结构域包含衔接诱导干扰素-β（TRIF）的表达。
结果
右美托咪定预处理显著预防了海马和皮质区 HE 和尼氏染色观察到的缺血诱导的细胞损伤。TUNEL 染色显示右美托咪定明显减少了凋亡细胞的数量。此外，育亨宾可特异性抑制右美托咪定的保护作用。右美托咪定预处理（10μg/kg、20μg/kg）明显抑制了脑缺血区 GFAP 的表达。右美托咪定预处理抑制了 TLR4 和 NF-κB 的表达，增加了 TRIF 的表达。
结论
本研究结果表明，右美托咪定预处理对 I/R 损伤具有神经保护作用。右美托咪定可能通过抑制 TLR4/NF-κB 通路，驱动 TLR4/TRIF 信号通路，减少炎症损伤。
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