Department of Surgery, Chi Mei Medical Center, Tainan, Taiwan.
J Trauma Acute Care Surg. 2012 May;72(5):1220-7. doi: 10.1097/TA.0b013e318246ee70.
We assessed whether hyperbaric oxygen preconditioning (HBO2P) in rats induced heat shock protein (HSP)-70 and whether HSP-70 antibody (Ab) preconditioning attenuates high altitude exposure (HAE)-induced brain edema, hippocampal oxidative stress, and cognitive dysfunction.
Rats were randomly divided into five groups: the non-HBO2P + non-HAE group, the HBO2P + non-HAE group, the non-HBO2P + HAE group, the HBO2P + HAE group, and the HBO2P + HSP-70 Abs + HAE group. The HBO2P groups were given 100% O2 at 2.0 absolute atmospheres for 1 hour per day for 5 consecutive days. The HAE groups were exposed to simulated HAE (9.7% O2 at 0.47 absolute atmospheres of 6,000 m) in a hypobaric chamber for 3 days. Polyclonal rabbit anti-mouse HSP-70-neutralizing Abs were intravenously injected 24 hours before the HAE experiments. Immediately after returning to normal atmosphere, the rats were given cognitive performance tests, overdosed with a general anesthetic, and then their brains were excised en bloc for water content measurements and biochemical evaluation and analysis.
Non-HBO2P group rats displayed cognitive deficits, brain edema, and hippocampal oxidative stress (evidenced by increased toxic oxidizing radicals [e.g., nitric oxide metabolites and hydroxyl radicals], increased pro-oxidant enzymes [e.g., malondialdehyde and oxidized glutathione] but decreased antioxidant enzymes [e.g., reduced glutathione, glutathione peroxide, glutathione reductase, and superoxide dismutase]) in HAE. HBO2P induced HSP-70 overexpression in the hippocampus and significantly attenuated HAE-induced brain edema, cognitive deficits, and hippocampal oxidative stress. The beneficial effects of HBO2P were significantly reduced by HSP-70 Ab preconditioning.
Our results suggest that high-altitude cerebral edema, cognitive deficit, and hippocampal oxidative stress can be prevented by HSP-70-mediated HBO2P in rats.
我们评估了高压氧预处理（HBO2P）是否会诱导大鼠热休克蛋白（HSP）-70 的产生，以及 HSP-70 抗体（Ab）预处理是否可以减轻高海拔暴露（HAE）引起的脑水肿、海马氧化应激和认知功能障碍。
大鼠随机分为五组：非 HBO2P + 非 HAE 组、HBO2P + 非 HAE 组、非 HBO2P + HAE 组、HBO2P + HAE 组和 HBO2P + HSP-70 Ab + HAE 组。HBO2P 组每天接受 100%氧气，在 2.0 绝对大气压下持续 1 小时，连续 5 天。HAE 组在低压舱中暴露于模拟 HAE（9.7%氧气，0.47 绝对大气压，海拔 6000 米）中 3 天。多克隆兔抗鼠 HSP-70 中和 Ab 在 HAE 实验前 24 小时静脉注射。回到正常大气后，立即对大鼠进行认知性能测试，过量使用全身麻醉，然后整块取出大脑进行含水量测量和生化评估分析。
非 HBO2P 组大鼠在 HAE 中表现出认知缺陷、脑水肿和海马氧化应激（表现为毒性氧化自由基增加[如一氧化氮代谢物和羟基自由基]，促氧化剂酶增加[如丙二醛和氧化型谷胱甘肽]，但抗氧化酶减少[如还原型谷胱甘肽、谷胱甘肽过氧化物酶、谷胱甘肽还原酶和超氧化物歧化酶]）。HBO2P 诱导海马 HSP-70 过度表达，并显著减轻 HAE 引起的脑水肿、认知缺陷和海马氧化应激。HSP-70 Ab 预处理显著降低了 HBO2P 的有益作用。
我们的结果表明，HSP-70 介导的 HBO2P 可预防大鼠高原脑水肿、认知缺陷和海马氧化应激。
