不同频率间歇低氧下大鼠肝脏氧化应激损伤及Tempol的干预作用

A study of rat liver oxidative stress injury with different frequencies intermittent hypoxia and the effect of Tempoi

目的探讨不同频率间歇低氧（IH）对大鼠肝脏氧化应激损伤差异和Tempol的干预作用及可能机制。方法应用慢性间歇低氧（CIH）大鼠模型，模拟OSAS周期性间歇低氧／再氧和病理生理过程。56只雄性Wistar大鼠随机分为不同频率IH组（IH1，IH2，IH3，IH4，频率依次为10、20、30、40次／h），30T组（30次／h低氧Tempol干预组），30N组（30次／h低氧生理盐水对照组），以及常氧对照组（NC组），共7组，每组8只，IH各组最低氧浓度均为5％。暴露6周后，测定大鼠肝脏丙二醛（MDA）、超氧化物歧化酶（SOD）、总抗氧化能力（T-AOC）的水平。结果①4个不同频率IH组MDA水平均高于NC组（P值均〈0．05），SOD、TAOC活性均低于NC组（P值均〈0．05），且随着IH频率的升高，MDA水平逐渐升高，SOD、T—AOC活性逐渐下降，除IH3组和IH4组MDA、SOD、T—AOC水平差异均无统计学意义外（P值均〉0．05），其余IH组两两比较，以上指标差异均有统计学意义（P值均〈0．05）。②与IH3组、30N组比较，30T组MDA水平下降（P〈0．05），SOD、T—AOC活性升高（P值均〈0．05），且与NC组比较差异无统计学意义（P值均〉0．05）。③不同频率IH组MDA水平与SOD、T-AOC活性均呈负相关（r分别为-0．721，-0．653，P值均=0．000）。结论不同频率CIH对大鼠肝脏氧化应激损伤的程度不同，但并不是频率越高，损伤越重；Tempol能预防CIH大鼠肝脏氧化应激损伤的发生。

Objective To study the effect of different frequencies intermittent hypoxia on malondialdehyde （MDA）, superoxide dismutase （SOD） and total antioxidant capacity （T-AOC）of rat liver and to investigate the effect of Tempol. Methods To establish a chronic intermittent hypoxia （CIH） animal model in rats,in order to mimic the intermittent hypoxia/reoxygenation （IH/ROX） of obstructive sleep apnea syndrome in humans. 56 healthy male Wistar rats were randomly assigned to seven groups：4 different IH frequencies groups （IH1：10 times/h, IH2：20 times/h, IH3：30 times/h,IH4：40 times/h with 5% O2）,the IH3＋Tempol group （30T group）,the IH3＋normal saline control group （30N group） and normoxia control group （NC group） ,each group of eight rats. After the experiment,we measured the levels of MDA,SOD and T AOC in rat liver homogenate. Results The level of MDA in 4 different IH frequencies groups was higher than in NC group （all P 〈0.05） ,the activity of SOD,T AOC were lower than in NC group （all P d0.05）. And there was a trend as the IH frequency increased,the level of MDA was gradually increased, the activity 9f SOI3 and T-AOC were gradually decreased. The differences of MDA, SOD,T-AOC level were statistical significant between each two different IH frequencies groups （all P 〈0.05） ,except the differences between IH3 group and IH4 group （all P 〉0.05）. Compared with IH3 group,30N group,the level of MDA in 30T group was decreased （ P -（0.05） ,the activity of SOD,T-AOC were increased （all P 〈0.05）,and the levels of MDA, SOD,T-AOC in 30T group were not significant with in NC group （all P 〉0.05）. The level of MDA in 4 different IH frequencies groups was negative correlation with the activity of SOD, T-AOC （ r were -0. 721, -0. 653 respectively, all P = 0. 000）. Conclusions Different CIH frequencies had different degrees of injury of oxidative stress on rat liver,but the relationship between the degree of injury on liver and the CIH frequencies was not entirely a linear. Tempol could prevent the oxidative stress injury on the rat liver of CIH.