Qin Z, Hua Y, Liu W, Silbergleit R, He Y, Keep R F, Hoff J T, Xi G
Department of Neurosurgery, Room 5018, BSRB, University of Michigan, Ann Arbor, MI 48109-2200, USA.
Acta Neurochir Suppl. 2008;102:317-20. doi: 10.1007/978-3-211-85578-2_60.
New protein synthesis is key to ischemic tolerance induced by preconditioning and ribosomal protein S6 kinases (p70 S6 K) are important enzymes in protein synthesis. Hyperbaric oxygen preconditioning (HBOP) reduces ischemic brain damage. This study investigated if HBOP can activate p70 S6 K and increase new protein synthesis and if HBOP induces brain tolerance against brain swelling after intracerebral hemorrhage (ICH).
There were two parts of the studies. 1) Rats received five consecutive sessions of HBOP. Twenty-four hours after HBOP, the rats had an ICH and were sacrificed one or three days later for brain edema measurement. 2) Rats received five sessions of HBOP or control pretreatment and were sacrificed for Western blot analysis and immunohistochemistry of activated p70 S6 K and heme oxygenase-1 (HO-1).
Five sessions of HBOP significantly reduced brain edema in the ipsilateral basal ganglia after ICH. Western blot analysis showed that HBOP activated p70 S6 K and increased HO-1 levels in the basal ganglia. Strong activated p70 S6 K immunoreactivity was also found in the basal ganglia.
Our results suggest activation of p70 S6 K may have a role in heat shock protein synthesis after HBOP and may contribute to HBOP-induced brain protection.
新蛋白质合成是预处理诱导的缺血耐受的关键,核糖体蛋白S6激酶(p70 S6 K)是蛋白质合成中的重要酶。高压氧预处理(HBOP)可减轻缺血性脑损伤。本研究调查了HBOP是否能激活p70 S6 K并增加新蛋白质合成,以及HBOP是否能诱导大脑对脑出血(ICH)后脑肿胀的耐受性。
研究分为两部分。1)大鼠连续接受5次HBOP治疗。HBOP治疗24小时后,大鼠发生ICH,并在1天或3天后处死以测量脑水肿。2)大鼠接受5次HBOP或对照预处理,然后处死进行Western印迹分析以及对活化的p70 S6 K和血红素加氧酶-1(HO-1)进行免疫组织化学分析。
5次HBOP治疗可显著减轻ICH后同侧基底神经节的脑水肿。Western印迹分析显示,HBOP可激活基底神经节中的p70 S6 K并提高HO-1水平。在基底神经节中也发现了强烈的活化p70 S6 K免疫反应性。
我们的结果表明,p70 S6 K的激活可能在HBOP后的热休克蛋白合成中起作用,并可能有助于HBOP诱导的脑保护。