急性高原缺氧大鼠肺组织损伤及其机制研究

Studies on lung damage and expressions of AQP1/4 in rats exposed to acute high-altitude hypoxia

【目的】通过建立低压缺氧模型,模拟急性高原缺氧损伤,观察不同缺氧时间点大鼠肺组织损伤情况。【方法】选取清洁级雌性SD大鼠60只,随机分为正常对照组、缺氧6、12及24 h组。利用数控低压缺氧舱,建立急性高原缺氧损伤模型,通过HE染色观察大鼠肺组织形态学改变,利用干湿比重法检测肺组织含水量,采用生化手段检测血清乳酸脱氢酶(lactatedehydrogenase,LDH)及过氧化氢酶(catalase,CAT)活性,应用Western blotting技术检测肺组织水通道蛋白(aquaporin,AQP)1/4的表达情况。【结果】HE染色:正常对照组可见多边形或圆形薄壁囊泡,边界清楚,肺泡上皮细胞间为薄壁肺泡隔,隔内可见毛细血管断面,各低压缺氧组肺泡上皮细胞明显肿大,肺泡壁增厚,肺间隔内毛细血管扩张;与正常对照组相比,各缺氧组大鼠肺含水量显著升高(P<0.01),且随缺氧时间的延长而逐渐增高;与正常对照组相比,各缺氧组大鼠血清LDH活性显著升高(P<0.01),CAT活性显著下降(P<0.05或P<0.01);与正常对照组相比,各缺氧组大鼠肺组织中AQP1/4蛋白表达量均明显升高(P<0.01),且随缺氧时间的延长而逐渐增高。【结论】急性高原缺氧可造成实验大鼠肺水肿,且损伤程度与缺氧时间密切相关,其机制可能为上调水通道蛋白(AQP)1/4的表达所致。

【Objective】 To investigate the lung damage and regulatory expressions of AQP1/4 in rats exposed to acute high-latitude hypoxia.【Methods】Sixty female Sprague-Dawley rats were randomly divided into control group and hypoxia groups of 6 h,12 h and 24 h.The rats in hypoxia group were put into a specially designed decompression chamber to simulate altitude of 7 000 m.After hypobaric hypoxia exposure,the morphological changes of lung were observed by HE staining,and the water contents in lung were determined by the wet-dry method.The biochemical indicators like LDH and CAT in lung tissue were detected with biochemistry method,and the expressions of AQP1 and AQP4 in lung tissue were determined individually by Western blot.【Results】The morphological changes of lung in hypoxia groups by HE staining revealled different degrees of cellular injury,including edema of lung epithelial cell,thickening of alveolar wall and enlarge of micrangium.With the increasing duration of hypoxia,the degree of lung damage became serious.Compared with control group,the water contents in lung were remarkably increased in hypobaric hypoxia groups（P 0.01）.With the injure duration increased,the water contents were increased remarkably.Compared with control group,the activities of LDH were remarkably increased（P 0.01）,and the activities of CAT were creased（P 0.05 or P 0.01） in rats serum of hypoxia groups.Compared with control group,the expressions of AQP1 and AQP4 in lung tissue were significantly increased（P 0.01） after hypobaric hypoxia exposure,and the up-regulation of AQP1 and AQP4 wereenhanced with the increasing duration of hypoxia.【Conclusion】Acute high-altitude hypoxia causes the severe damages of lung tissue,such as cerebral edema,which is correlated with up-regulated expressions of AQP1 and AQP4.