褪黑激素对大鼠缺血/再灌注所致脑损伤的保护机制

目的：研究褪黑激素（melatonin, MT）对大鼠全脑缺血（20 min）再灌注后24 h海马CA1区诱导型一氧化氮合酶（inducible nitric oxide synthase , iNOS）的蛋白质水平和再灌注后48h海马CA1区TUNEL阳性细胞数的影响。方法：于大鼠“四动脉结扎法”全脑缺血（20 min）/再灌注后第0、1、2、6小时4个时间点分别腹腔注射MT2.5和10 mg*kg－1两个剂量，各组大鼠再灌后24 h后用免疫细胞化学法检测海马CA1区iNOS蛋白水平，用末端脱氧核糖核苷酸转移酶介导的dUTP缺口末端标记法（TDT mediated dUTP nick end labling, TUNEL）计算了各组大鼠再灌后48 h海马CA1区TUNEL阳性细胞数。结果：MT2.5 mg*kg－1和10 mg*kg－1两个剂量于大鼠全脑缺血（20 min）/再灌注后第0、1、2、6小时4个时间点分别腹腔注射可降低再灌注24 h大鼠海马CA1区iNOS的蛋白水平，并减少再灌注48 h海马CA1区TUNEL阳性细胞数。结论：降低iNOS的蛋白质水平可能是MT对缺血敏感区神经细胞发挥保护效应的机制之一。

The mechanism of protective effects of melatonin on global ischemia/reperfusion induced brain injury in rats

Objective: To study the effects of melatonin（MT） on inducible nitric oxide synthase (iNOS) expression in hippocampal CA1 at 24 hours and TDT-mediated dUPT nick end labling (TUNEL) positive cells in hippocampal CA1 at 48 hours after global ischemia（20 min）/ reperfusion in rats. Methods: MT was injected intraperitoneally at 0 h, 1 h, 2 h and 6 h after ischemia（20 min） induced by the“occlusion of four arteries”, 2.5 mg*kg－1 or 10 mg*kg－1 each time, respectively. Researching the expression of iNOS in hippocampal CA1 with the immunocytochemistry method 24 hours after reperfusion and the number of TUNEL positive cells in hippocampal CA1 48 hours after reperfusion utilizing TUNEL. Results: At these doses, MT could decrease iNOS expression in hippocampal CA1 at 24　h after global ischemia （20 min）/reperfusion and the number of TUNEL cells in hippocampal CA1 at 48h after reperfusion in rats. Conclusion: Decreasing the expression of deleterious iNOS maybe one of the mechanisms involved in protective action of MT on ischemia-vulnerable brain region.