右美托咪啶预处理经AMPK/SIRT1通路抑制大鼠脑缺血再灌注损伤的炎性反

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Abstract Objective To investigate the mechanism of Dexmedetomidine (Dex) pretreatment on inflammation after cerebral ischemia/reperfusion (I/R) injury in rats. Methods Seventy-two SD rats were randomly divided into 6 groups (n=12). In sham group, after anesthesia by 3% Pentobarbital sodium (50 mg/kg), the rates were isolated the right internal carotid artery, but they were not made into the middle cerebral artery occlusion (MCAO) model. In IR group, after the molding, the rat brain was received reperfusion at 90 min after ischemia. In Dex10 and Dex50 groups, after the molding, they were intraperitoneal injected Dex (10 μg/kg or 50 μg/kg) at 30 min before ischemia. In Dex50+Yoh group, after the molding, they were intraperitoneal injected Yoh (0.5 mg/kg) before 50 μg/kg of Dex. In Yoh group, after the molding, they were intraperitoneal injected Yoh (0.5 mg/kg) before ischemia. The neurofunctional damage assessment, infarct area assessment, the levels of TNF-α and IL-1β, TUNEL staining, SIRT1 protein detection and Neuro-motor function score (TMS) in each group were detected respectively. Results In the IR group, neurofunctional scores, infarction area, TUNEL (+) cell count, levels of TNF-a and IL-1 β and SIRT1 protein expression were significantly higher than those in the sham group, while the TMS scores at 1, 2 and 5 days after reperfusion were lower than those in the sham group, with highly statistically significant difference (P < 0.01). The neurofunctional scores, infarction area, TUNEL (+) cell count, and TNF-a and IL-1 β levels in the Dex10 group and Dex50 group were significantly lower than those in the IR, Dex50+YOH and YOH group, while the TMS score and SIRT1 protein expression were higher than those in the IR, Dex50+YOH and YOH group, with highly statistically significant difference (P < 0.01). The nerve function scores, infarction area, TUNEL (+) cell count, and TNF-a and IL-1 β levels in the Dex50 group were significantly lower than those in the Dex10 group, TMS score and SIRT1 protein expression were significantly higher than those in the Dex10 group (P < 0.01). There was no statistically significant difference between the test indexes of Dex50+YOH group and YOH group (P > 0.05). Conclusion Dexmedetomidine preconditioning can activate α2 adrenergic receptor through AMPK/SIRT1 pathway to inhibit cerebral ischemia reperfusion injury in rats, and reduce the inflammation.

Key words： Dexmedetomidine Inflammation Reperfusion injury Brain ischemia

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	DONG Haiping ZHOU Wei WANG Zhenhong HE Zhenzhou▲

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DONG Haiping ZHOU Wei WANG Zhenhong HE Zhenzhou▲. Dexmedetomidine pretreatment inhibits the cerebral ischemia/reperfusion-induced neuroinflammation via AMPK/SIRT1 pathway in rats[J]. 中国医药导报, 2018, 15(1): 4-9.

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