昼夜节律对大鼠局灶性脑缺血再灌注损伤的影响

Effect of circadian rhythm on local cerebral ischemia-reperfusion injury in rats

目的观察昼夜节律对大鼠局灶性脑缺血再灌注损伤的影响。方法将大鼠置人工光(6:00-18:00)暗(18:00-6:00)环境中,适应性饲养4周。然后将大鼠随机分为6:00组、12:00组、18:00组和24:00组,分别在相应的时间点采用线栓法制备局灶性脑缺血再灌注损伤大鼠模型。再灌注24 h后,观察昼夜节律对模型大鼠神经损伤症状,脑梗死范围,脑组织超氧化物歧化酶(SOD)活性和MDA含量,脑细胞内游离Ca2+浓度,血清中内皮素(ET)和血管内皮细胞生长因子(VEGF),以及脑组织病理变化的影响。结果各组大鼠均具有明显的神经损伤症状,其中24:00组大鼠的神经损伤症状明显轻于6:00组;6:00、12:00组大鼠脑梗死范围明显大于18:00、24:00组;18:00、24:00组大鼠SOD活性均显著高于6:00、12:00组,MDA含量均显著低于6:00组;24:00组大鼠脑细胞内游离Ca2+浓度显著低于6:00和12:00组,18:00组大鼠脑细胞内游离Ca2+浓度显著低于6:00;18:00、24:00组大鼠血清ET含量显著低于6:00组大鼠;24:00组大鼠血清VEGF含量显著低于6:00、12:00组;18:00、24:00组大鼠脑组织病理变化明显轻于6:00、12:00组。结论昼夜节律对大鼠脑缺血再灌注损伤具有显著影响。

Objective To observe the effect of circadian rhythm on local cerebral ischemia-reperfusion injury in rats. Methods One hundred SPF male SD rats （body weight 320 ＋ 20 g） were raised in light（6：00 - 18：00） -dark （ 18： 00-6：00） cycle environment for 4 weeks. Then all rats were randomly divided into 6：00 group, 12：00 group, 18：00 group and 24：00 group. Rat models of cerebral ischemia-reperfusion injury were induced by middle cerebral artery occlu- sion at corresponding time points for each group. The neurological symptoms were evaluated, cerebral infarction area and SOD and MDA levels in brain tissue were determined, intracellar Ca2 ＋ concentration of brain tissue was measured, the level of serum endothelin （ET） and VEGF were assayed, and the pathological changes of brain tissue at 24 h after ischemia- reperfusion were examined. Results All rats showed typical neurological symptoms, which were milder in the 24：00 group than that of the 6：00 group, and the cerebral infarction areas of the 6：00 group and 12：00 group were significantly larger than that of the 18：00 group and 24：00 group. The SOD activities of 18：00 group and 24：00 group were significantly high- er than that of the 6：00 group and 12：00 group, and the MDA levels of 18：00 group and 24：00 group were significantly lower than that of the 6：00 group and 12：00 group. The concentration of intracellular Ca2＋ of the 24：00 group was lower than that of 6：00 group and 12：00 group, and the concentration of intracellular Ca^2＋ of the 18：00 group was significantly lower than that of the 6：00 group. The contents of serum ET in the 18：00 group and 24：00 group were significantly lower than that in the 6：00 group. The content of serum VEGF of 24：00 group was obviously lower than that of the 6：00 group and 12：00 group. The brain pathological changes of the 18：00 group and 24：00 group were obviously milder than that of the 6：00 group and 12：00 group. Conclusion Circadian rhythm may significantly influence the cerebral ischemia-reper- fusion injury in rats.