基于氧化应激及水通道蛋白探讨高原低氧暴露对大鼠脑损伤的影响  

Effects of high-altitude hypoxia exposureon brain injury in rats based on oxidative stress and aquaporins

作　　者：张鑫珏 曹旺杰 苏韫 龚红霞[1,2,3] 黄勇 刘永琦 和建政 郭家旺[1,2,3] 张能贤 ZHANG Xin-jue;CAO Wang-jie;Su Yun;GONG Hong-xi;HUANG Yong;LIU Yong-qi;HE Jian-zheng;GUO Jia-wang;ZHANG Neng-xian(School of Basic Medicine,Gansu University of Chinese Medicine,Lanzhou 730101,Gansu Province,China;Key Laboratory of Molecular Medicine and Traditional Chinese Medicine Prevention and Treatment for Major Diseases in Higher Education Institutions in Gansu Province,Lanzhou 730000,Gansu Province,China;DunhuangKey Laboratory of Medicine and Translational Education of the Ministry of Education,Lanzhou 730000,GansuProvince,China)

机构地区：[1]甘肃中医药大学基础医学院,甘肃兰州730101 [2]甘肃省高校重大疾病分子医学与中医药防治研究重点实验室,甘肃兰州730000 [3]敦煌医学与转化教育部重点实验室,甘肃兰州730000

出　　处：《中国临床药理学杂志》2025年第1期81-85,共5页The Chinese Journal of Clinical Pharmacology

基　　金：甘肃省自然科学基金资助项目(23JRRA1210);甘肃省高等学校青年博士基金资助项目(2022QB-102);甘肃省教育厅高等学校科技创新基金资助项目(2023A-087);兰州市科技计划基金资助项目(2022-2-106);甘肃中医药大学引进人才科研启动基金资助项目(2023YJRC-06)。

摘　　要：目的探讨不同时间点低压低氧暴露下SD大鼠的脑损伤情况。方法用低压低氧动物实验舱模拟海拔6000m构建大鼠高原脑水肿(HACE)模型。将36只SD雄性大鼠随机分为对照组和低压低氧暴露3、7、14d组,每组9只。除对照组外,其余各组大鼠分别连续低压低氧暴露3、7、14d。造模结束后,经腹主动脉取血,收集血清并取其脑组织样本。计算脑组织湿干比(W/D),检测血清和脑组织中相关氧化酶含量,用实时荧光定量聚合酶链反应法检测脑组织中低氧诱导因子-1α(HIF-1α)和水通道蛋白4(AQP4)mRNA的表达水平。结果对照组和低压低氧暴露3、7、14d组的脑组织W/D分别为4.46±0.12、4.98±0.16、5.07±0.18和4.95±0.07,超氧化物歧化酶含量分别为(111.86±2.45)、(90.73±1.48)、(79.64±2.56)和(55.33±1.45)U·g^(-1),谷胱甘肽含量分别为(126.91±5.18)、(125.26±1.53)、(56.20±2.17)和(122.73±1.78)μg·mL^(-1),丙二醛含量分别为(230.94±2.00)、(362.65±3.28)、(407.34±3.47)和(237.50±1.59)nmol·g^(-1),HIF-1α mRNA相对表达水平分别为1.00±0、2.99±0.49、4.72±0.49和1.91±0.28,AQP4 mRNA相对表达水平分别为1.00±0、2.62±0.34、8.38±0.84和5.27±0.42。低压低氧暴露3、7、14d组的上述指标与对照组比较,在统计学上差异均有统计学意义(P<0.05,P<0.01)。结论不同低压低氧暴露时间均可以上调HACE大鼠AQPs蛋白的表达并造成血脑屏障的破坏,且在低压氧舱6000m干预7d构建的HACE模型较为稳定。Objective To explore the brain damage of SD rats under different time points of hypobaric hypoxia exposure.Methods A rat high-altitube cerebral edema(HACE)model was constructed by simulating an altitude of 6000 m in a hypobaric hypoxia animal experimental chamber.Thirty-six SD male rats were randomly divided into the control group and the hypobaric hypoxia exposure 3,7 and 14 d groups,with 9 rats in each group.Except for the control group,the rats in each group were continuously exposed to hypobaric hypoxia for 3,7,and 14 d.At the end of the modeling period,serum was collected by blood sampling via the abdominal aorta,and brain tissue samples were taken.The wet-to-dry ratio(W/D)of brain tissue was calculated,and the levels of relevant oxidative enzymes in serum and brain tissue were measured.The expression levels of hypoxia-inducible factor-1α(HIF-1α)and aquaporin 4(AQP4)mRNAs in brain tissue were detected by real-time fluorescence quantitative polymerase chain reaction.Results The W/D of brain tissues in the control group and the group exposed to hypobaric hypoxia for 3,7 and 14 d were 4.46±0.12,4.98±0.16,5.07±0.18 and 4.95±0.07;the superoxide dismutase contents were(111.86±2.45),(90.73±1.48),(79.64±2.56)and(55.33±1.45)U·g^(-1);the glutathione contents were(126.91±5.18),(125.26±1.53),(56.20±2.17)and(122.73±1.78)μg·mL^(-1);the malondialdehyde contents were(230.94±2.00),(362.65±3.28),(407.34±3.47)and(237.50±1.59)nmol·g^(-1);the relative expression levels of HIF-1α mRNA were 1.00±0,2.99±0.49,4.72±0.49 and 1.91±0.28;the relative expression levels of AQP4 mRNA were 1.00±0,2.62±0.34,8.38±0.84 and 5.27±0.42,respectively.Statistically significant differences were found between the above indexes in the 3,7 and 14 d of hypobaric hypoxia exposure group compared with the control group(P<0.05,P<0.01).Conclusion Different time of hypobaric hypoxia exposure can up-regulate the expression of AQPs proteins in HACE rats and cause the disruption of the blood-brain barrier,and the HACE model construct

关 键 词：水通道蛋白 高原低氧 高原脑水肿 氧化应激 血脑屏障 

分 类 号：R97[医药卫生—药品]