Objective To compare the protective effect of hypobaric hypoxic preconditioning (HHPC) and normobaric hypoxic preconditioning (NHPC) on the decline of motor coordination induced by acute altitude hypoxia exposure in mice.Methods Forty-eight male Kunming mice (KM) were divided into 3 groups by body weight block randomization: control group (CON), HHPC group (HHPC) and NHPC group (NHPC). HHPC group was trained in a hypobaric chamber (mimicking 5000 m high altitude), 4 h/d for 7 d while NHPC group was trained in a normobaric chamber (simulating 5000 m high altitude), 4 h/d for 7 d. After 7 days of hypoxic preconditioning, motor coordination of the mice was measured by the coat-hanger (CH) test both at sea level and upon acute exposure to 5000 m altitude. The protein expression of hypoxia inducible factor-1α (HIF-1α) in the brain was determined by Western blot, and the localization of HIF-1α was detected using immunohistochemistry.Results ①The score of body position revealed significant effects on altitude (at both sea level and 5000 m altitude), hypoxic preconditioning (HPC) and altitude×HPC interactions. Latency taken to reach the end of the horizontal bar showed a significant effect on altitude but not on HPC or altitude×HPC interactions.Latency to fall off revealed significant effects on altitude, HPC and altitude×HPC interactions.②Western blot analysis showed that the expression of HIF-1α was significantly upregulated (P<0.01) in the brain in HHPC and NHPC, compared with CON, and HIF-1α expression was much higher in NHPC than in HHPC.③Immunohistochemical staining showed that the positive cells were dyed brown, which were mostly located in the cortex, and that the number of positive cells increased in both HHPC and NHPC compared with CON, especially in NHPC.Conclusion Motor coordination can be affected when mice are exposed to acute altitude hypoxia. Both HHPC and NHPC exert protective effects on the decline of motor coordination induced by acute altitude hypoxia exposure in mice. NHPC might protect motor coordination better than HHPC against acute hypoxia exposure. The level of HIF-1α expression in the cortex may play an important role in these protective effects.%目的 比较短期低压缺氧预处理(hypobaric hypoxic preconditioning,HHPC)与常压缺氧预处理(normobaric hypoxic preconditioning,NHPC)对小鼠急性高空缺氧暴露所导致的协调运动能力下降的保护效应.方法 48只雄性昆明小鼠按体质量区组随机划分为3组:对照组(CON组)、低压缺氧预处理组(HHPC组)和常压缺氧预处理组(NHPC组),分别采用小动物低压舱与低氧混合气法模拟5000 m高空缺氧环境进行缺氧预处理,4 h/d,连续7 d.7 d后分别在地面条件和低压舱5000 m急性暴露时进行衣架实验;蛋白印迹技术检测脑组织中缺氧诱导因子-1α(hypoxia inducible factor-1α,HIF-1α)蛋白表达;免疫组化法观察脑组织HIF-1α蛋白表达定位与变化.结果 ①衣架实验得分、从衣架上掉落的潜伏时间显示,暴露高度(地面条件和5000 m急性高空)、不同的缺氧预处理方式及二者之间的交互作用均有显著性影响(P<0.05);到达水平部末端的潜伏时间提示暴露高度有显著性影响,而不同的缺氧预处理方式及二者之间的交互作用差异无统计学意义.②蛋白印迹结果显示,与CON相比,HHPC、NHPC组脑组织HIF-1α表达均显著增加(P<0.01),且NHPC组增加比HHPC组更为明显(P<0.05).③免疫组化蛋白定位显示,HIF-1α蛋白棕黄色阳性表达主要位于大脑皮质,阳性细胞数量NHPC组>HHPC组,而HHPC组>CON组.结论 5000 m急性高空缺氧可明显降低各组小鼠的协调运动能力;HHPC、NHPC均能对小鼠急性高空缺氧暴露所致的协调运动能力下降产生防护效应,但NHPC组比HHPC组在急性高空缺氧暴露时表现出更好的运动协调能力,其保护效应的差异可能与NHPC脑皮质HIF-1α表达水平相关.
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