右美托咪定对脓毒症小鼠的脑保护作用

The protective effects of dexmedetomidine on sepsis -associated encephalopathy in mice

目的探讨右美托咪定对脓毒症小鼠存活率的影响及脑保护作用并探讨其机制。方法ICR雄性小鼠,体质量20~25g,采用随机数字表法分为四组(n=20):假手术(Sham)组、脓毒症(CLP)组、脓毒症+右美托咪啶(CLP+DEX)组及脓毒症+右美托咪啶+育亨宾(CLP+DEX+Y)组。CLP组通过盲肠结扎穿孔术(CLP)制备脓毒症小鼠模型,Sham组不进行盲肠结扎和穿孔,其余处理与模型组相同。CLP+DEX组于模型制备后0、2、4、6h分别腹腔注射10μg/kg右美托咪定,CLP+DEX+Y组除术后右美托咪定治疗还需于模型制备前30min腹腔注射育亨宾3mg/kg,其他组给予等量生理盐水。于术后24h取小鼠脑组织,对其分别进行脑组织含水量、脑组织匀浆中丙二醛(MDA)含量及超氧化物歧化酶(SOD)活性、脑组织病理和脑细胞凋亡情况的检测。结果CLP组小鼠脑组织含水量增加,脑组织匀浆中MDA含量明显增加,SOD活性明显降低,组织病理学细胞破坏增多、TUNEL染色阳性细胞数增多,10μg/kg的右美托咪啶治疗可使这些变化明显缓解(P<0.05)。育亨宾能拮抗右美托咪定的保护效果。结论右美托咪定通过作用于Ⅸ:肾上腺素受体对脓毒症小鼠脑损伤有明显的保护作用,其机制可能与其抗凋亡作用以及对内源性氧化还原平衡状态的维持有关。

Objective This study aims to investigate the effects of dexmedetomidine (DEX)on the survival rate and brain injury using a mice model of sepsis -associated encephalopathy (SAE). Methods Male ICR mice weighing 20-25g were randomly divided into 4 groups :Sham,CLP,CLP + DEX and CLP + DEX + Y groups.Mice underwent cecal ligation and puncture (CLP)or sham operation.DEX (10μg/kg)was injected 4 times (0,2,4,6h)after CLP operation in group CLP + DEX and group CLP +DEX +Y.Yohimbine (3mg/kg)was given to group CLP +DEX +Y 30 min before operation.Brain water content,activities of SOD and levels of MDA in hippocampus were detected.HE staining,Nissl staining and TUNEL assay were used to observe the histopathologic changes and neuronal apoptosis.Results DEX treatment markedly alleviated pathological damage and brain edema caused by CLP operation.Levels of oxidative pmducts decreased and the activities of antioxidant enzymes increased in brain.Yohimbine can counteract the effect of DEX.Conclusion DEX targets on adrenergic α2 receptors to show the brain protective effect,which is linked to the decreased levels of oxidative products and the increased activities of antioxidant enzymes in brain.DEX may be a promising therapeutic strategy to relieve SAE.