急性缺氧缺血后亚低温对新生鼠脑能量代谢的影响

目的:研究亚低温治疗对缺氧缺血脑损伤(HIBD)新生大鼠的脑组织葡萄糖、ATP水平的影响及对脑线粒体琥珀酸脱氢酶(SDH)、复合酶II的活性及ATP合成能力的影响,以探讨亚低温的神经保护机制。方法:将HIBD模型鼠随机分为缺氧缺血(HI)常温恢复组和亚低温干预组,同时设对照组。各组动物在HI后不同时点(0、2、6、24、48、72h)断头取脑,测定脑匀浆葡萄糖及ATP含量;用密度离心及差速离心法提取线粒体,生化法测定脑线粒体琥珀酸脱氢酶(SDH)和复合酶II的活性,并用酶萤光法检测脑线粒体的ATP合成能力。结果:缺氧缺血常温恢复组脑组织匀浆葡萄糖在HI后即刻明显低于HI前,HI后2h与HI前无显著差异。脑ATP的量及SDH活性在HI后2、6h先下降后恢复,72h达高峰但仍明显低于正常;脑线粒体复合酶II的活性及脑线粒体ATP合成能力在HI后2h开始恢复,6h出现第二次下降,72h与正常无显著差异。亚低温干预组各时点脑组织ATP、脑线粒体SDH活性、脑线粒体复合酶II的活性及ATP的合成能力均显著高于同一时点常温组,ATP在24h与正常对照组无明显差异,SDH在72h与正常对照组无明显差异,复合酶II在48h与正常对照组无明显差异,ATP合成能力在24h与正常对照组无明显差异。结论:亚低温可减轻HIBD大鼠脑组织ATP含量、线粒体SDH及复合酶II活性的下降,增加脑ATP的合成,改善能量代谢,从而保护脑组织。

Moderate hypothermia post hypoxia-ischemia improves the cerebral energy metabolism in the immature rats

AIM: To study the effect of moderate hypothermia on immature rats with hypoxic-ischimic brain damage (HIBD). METHODS: The rats with HIBD were divided into normothermic recovered group (IN) and moderate-hypothermic recovered group (IH). Sham-operated rat pups were normothermic control group (NC) and moderate-hypothermic control group (HC). 0, 2, 6, 24, 48, 72 h after the end of hypoxic-ischemic (HI) insult, the brain was homogenized for measuring glucose and ATP, brain mitochondria was extracted for SDH activity, complex II activity and the capacity of ATP synthesization. RESULTS: In IN group, the brain glucose was significantly lower at 0 h, and recovered as normal at 2 h. The brain ATP and brain-mitochondrial SDH activities were firstly decreased at 2 h, 6 h and then recovered gradually, it was at it's peak value at 72 h. Brain-mitochondrial complex II activity and the capacity of ATP synthesis were recovered at 2 h, but they decreased again at 6 h and came to normal level at 72 h. In moderate-hypothermic group, all the indexes were significantly higher at all the time point than that in IN groups. CONCLUSION: Moderate hypothermia inhibits the decrease in the mitochondrial SDH activity, mitochondrial complex II activity and the capacity of ATP synthesis, increases the brain ATP concentration, improves the energy metabolism, and then protects the brain tissue.