高原低氧环境气虚小鼠肾、骨和脑组织反应性变化的分子机制研究

摘要

Objective To observe the molecular mechanism of adaptive response of the kidney and skeleton and brain issues in the high altitude hypoxia; To discuss the unity of yin and yang oscillation relationship of kidney and brain marrow.Methods SPF KM mice were randomly divided into control group and model group according to random number table method. Mice in the model group were exposed to high altitude hypoxia cabin for successive 21 d. On the 22nd day, mice got out of the cabin and their body weight was measured, and then they were put to death through eyeball blood sampling. The activities of lactic LDH and Na+-K+-ATPase in brain tissue were detected by spectrophotometric colorimetry. The PFK activities of brain and skeletal muscle were detected by ELISA. Meanwhile the contents of EPO and EPOR in the kidney were measured by ELISA. The mRNA expressions of HIF-1α and AQP-4 in brain were assessed by RT-PCR. At the same time, the protein expressions of HIF-1α and AQP-1 in brain and the protein expression of Mb in skeletal muscle were detected by Western blot.Results Compared with the normal group, the LDH and PFK in brain tissue and the content of EPO in kidney tissue were all raised in the model group(P<0.05). Meanwhile the mRNA expressions of HIF-1α and AQP-4 and the protein expressions of HIF-1α and AQP-1 in brain were all increased in the mice from the model group; the activities of PFK and the protein expression of Mb in skeletal muscle were also raised in the model group. But the activity of Na+-K+-ATPase in brain tissue and the content of EPOR in kidney tissue both decreased in the model group (P<0.05,P<0.01).Conclusion Adaptive response and the unity of yin and yang oscillation relationship between kidney, skeleton and brain tissue happen in high altitude hypoxia.%目的：观察高原低压低氧环境中小鼠肾、骨、脑组织的适应性反应分子机制，探讨肾与脑髓的阴阳上下升降互济的统一性。方法将 SPF 级小鼠采用随机数字表法分为正常对照组、模型组。模型组小鼠于低氧舱中模拟高海拔环境进行低氧暴露，连续21 d。第22日出舱称重后眼球采血处死小鼠。比色分析法检测各组小鼠脑组织乳酸脱氢酶（LDH）及Na+-K+-ATP酶活性。ELISA检测各组小鼠脑、骨骼肌组织磷酸果糖激酶（PFK）活性及肾组织促红细胞生成素（EPO）及其受体（EPOR）的含量。RT-PCR检测各组小鼠脑组织缺氧诱导因子-1α（HIF-1α）和水通道蛋白（AQP）-4 mRNA表达，Western blot检测脑组织HIF-1α、AQP-1及骨骼肌组织肌红蛋白（Mb）蛋白表达。结果与正常对照组比较，模型组小鼠肾组织 EPO 含量升高，脑组织LDH、PFK活性增强(P＜0.05)、HIF-1α和AQP-4的mRNA和蛋白表达水平升高（P＜0.05，P＜0.01）；模型组小鼠骨骼肌组织 PFK 活性增强和 Mb 蛋白表达水平升高（P＜0.05），脑组织 Na+-K+-ATP 酶活性和肾组织EPOR 含量降低（P＜0.05，P＜0.01）。结论高原低压低氧环境小鼠肾、骨和脑组织均发生了阴阳上下升降互济的适应性反应。