还原型辅酶Ⅱ氧化酶抑制剂对慢性间歇缺氧大鼠血压的影响及相关机制

目的 探讨还原型辅酶Ⅱ(NADPH)氧化酶抑制剂罗布麻宁对慢性间歇缺氧(CIH)模型大鼠血压可能的影响及相关作用机制.方法 使用随机数字表法将30只雄性SD大鼠分为健康对照组、CIH组及罗布麻宁治疗组,每组10只.采用气囊加压法测定大鼠尾动脉收缩压,应用实时PCR检测外周血单核细胞NADPH氧化酶亚基p22phox的mRNA表达,并用Western blot检测胸主动脉组织匀浆中p22phox蛋白的表达,采用比色法测定胸主动脉组织匀浆中一氧化氮及超氧阴离子含量,采用化学比色法测定大鼠外周血丙二醛及超氧化物歧化酶(SOD)水平.各组均数之间比较采用单因素方差分析,组内两两比较采用SNK-q检验.结果 CIH组p22phox mRNA(2.85±0.47)及其蛋白(0.63±0.15)的表达明显高于健康对照组(2.26±0.48,0.27 ±0.13,q值分别为3.202、6.522,均P＜0.05),罗布麻宁治疗组p22phox mRNA(2.75±0.50)及其蛋白(0.57±0.16)的表达与CIH组比较两组无明显差异,但治疗后可显著逆转由慢性间歇缺氧导致的丙二醛、超氧阴离子及尾动脉收缩压的升高以及SOD和一氧化氮水平的降低.结论 NADPH氧化酶亚基p22phox的过度表达在慢性间歇缺氧导致的高血压发生过程中起重要作用,这可能是OSAHS患者并发高血压的病理生理基础之一;抑制NADPH氧化酶的活性可能对OSAHS合并高血压的治疗有一定积极的意义.

Effect of NADPH oxidase activity inhibitor apocynin on blood pressure in rats exposed to chronic intermittent hypoxia and the possible mechanisms

Objective To investigate the effect of NADPH oxidase activity inhibitor apocynin on the blood pressure of rats exposed to chronic intermittent hypoxia (CIH).Methods Thirty healthy male SD rats were randomly divided into 3 groups of 10 each,a CIH group,an apecynin treatment group and a control group.The systolic blood pressure (SBP) was measured with tail-cuff method.RT-PCR and Western blot were used to examine mRNA and protein expression of NADPH oxidase subunit p22phox.The level of MDA,SOD,NO and ·O2-were detected by eoiorimetric method.ResultsCompared to the normal group,the expression of p22phox mRNA and protein were significantly increased in CIH group ( q = 3.202,6.522,P ＜0.05 ).There were no statistic difference of p22phox mRNA and protein expression between CIH group and apocynin treatment group ( P ＞ 0.05 ).Compared with those of CIH group,the levels of MDA,·O2-and the systolic blood pressure decreased significantly.( P ＜ 0.05 ),while SOD and NO activity increased significantly ( q = 6.960,4.385,P ＜ 0.05 ) in apocynin treatment group.Conclusions These results indicate that NADPH oxidase up-expression is closely associated with hypertension in OSAHS.Inhibition of NADPH oxidase activity may be hopefully served as a useful strategy for prevention and treatment of OSAHS induced hypertension.