慢性间歇低氧大鼠的血压变化及其颈动脉体中还原型烟酰胺腺嘌呤二核苷酸磷酸氧化酶的表达

目的 探讨慢性间歇低氧(chronic intermittent hypoxia,CIH)大鼠的血压变化及其颈动脉体中还原型烟酰胺腺嘌呤二核苷酸磷酸(NADPH)氧化酶的表达情况,以明确CIH致血压升高的可能机制.方法 清洁级雄性SD大鼠30只按随机数字表法分为CIH组、慢性持续缺氧组及对照组.尾袖法测量大鼠尾动脉收缩压,采用RT-PCR法检测大鼠颈动脉体中NADPH氧化酶各亚基gp91 phox、p22phox及p47phox mRNA的表达,对颈动脉体行免疫组织化学染色,并对p22phox的表达情况行半定量分析.结果 CIH组大鼠的尾动脉收缩压为[(145±11)mm Hg,1 mm Hg=0.133kPa],较CIH组(129±9)mm Hg及对照组(124±7)mm Hg显著升高(F值为19.895,P＜0.01),CIH组gp91phox、p22phox及p47phox mRNA的表达(分别为2.82±0.51、2.74±0.45和2.88±0.47)较慢性持续缺氧组(分别为2.35±0.42、2.25±0.38和2.41±0.43)及对照组(分别为2.23±0.35、2.16±0.30和2.30±0.36)显著升高(F值分别为5.794、6.854和7.163,P＜0.01)免疫组织化学检查结果显示CIH组p22phox蛋白相对表达量(99±12)较其他两组(分别为38±7和34±8)增多.结论 CIH可刺激大鼠颈动脉体中NADPH氧化酶的表达上调并使血压升高,NADPH氧化酶在颈动脉体中的过度表达可能与OSAHS患者发生高血压病存在相关联系.

Abstract：

Objective Chronic intermittent hypoxia (CIH) occurs in patients with obstructive sleep apnea-hyponea syndrome (OSAHS) and has adverse effects on multiple physiological functions. Previous studies have shown that reflexes arising from carotid bodies mediate CIH evoked circulation-respiratory responses, and reactive oxygen species (ROS) play important roles in eliciting systemic responses to CIH.But very little is known about the molecular mechanisms underlying CIH. NADPH oxidase is the most important sources of ROS. In the present study we examined changes of blood pressure and expression of NADPH oxidase in carotid body in rats exposed to intermittent hypoxia. Methods Thirty healthy male SD rats were randomly divided into 3 groups, a CIH group, a chronic continuous hypoxia group and a control group. The systolic blood pressure (SBP) was measured with tail-cuff method. RT-PCR was used to examine mRNA expressions of NADPH oxidase subunit gp91phox, p22phox, p47phox. Immunohistochemistry and semiquantitative analysis of NADPH oxidase subunits p22phox were done in the carotid body sections of all rats. Results Compared with normal group [ ( 124 ± 7 ) mm Hg, 1 mm Hg = 0. 133 kPa ] and chronic continuous hvpoxia group[ (129 ± 9) mm Hg], the SBP in CIH group [( 145 ± 11 ) mm Hg] was significantly higher( F = 19. 895, P ＜0. 01 ＝, and the expression of NADPH oxidase subunits gp91phox,p22phox,p47phox mRNA in CIH group ( 2. 82 ± 0. 51, 2. 74 ± 0. 45, 2. 88 ± 0. 47, respectively ) were significantly higher than those in chronic continuous hypoxia group ( 2. 35 ± 0. 42, 2. 25 ± 0. 38, 2. 41 ±0. 43, respectively)and normal group(2. 23 ±0. 35, 2. 16 ±0. 30, 2. 30 ±0. 36, respectively) ( F =5.794,6. 854, 7. 163, respectively, P ＜ 0. 01 ). The Immunohistochemistry and semiquantitative analysis showed that the expression of NADPH oxidase subunit p22phox in the carotid body in CIH group ( 99 ± 12 ) were more than those in chronic continuous hypoxia and control groups ( 38 ± 7 and 34 ± 8, P ＜ 0. 05 ).Conclusion CIH upregulates the expression of NADPH oxidase in rat carotid body and elevates the rat SBP. These results indicate that NADPH oxidase up-expression is closely associated with OSAHS patients with hypertension.

Changes of blood pressure and expression of NADPH oxidase in carotid body in rats exposed to intermittent hypoxia

Objective Chronic intermittent hypoxia (CIH) occurs in patients with obstructive sleep apnea-hyponea syndrome (OSAHS) and has adverse effects on multiple physiological functions. Previous studies have shown that reflexes arising from carotid bodies mediate CIH evoked circulation-respiratory responses, and reactive oxygen species (ROS) play important roles in eliciting systemic responses to CIH.But very little is known about the molecular mechanisms underlying CIH. NADPH oxidase is the most important sources of ROS. In the present study we examined changes of blood pressure and expression of NADPH oxidase in carotid body in rats exposed to intermittent hypoxia. Methods Thirty healthy male SD rats were randomly divided into 3 groups, a CIH group, a chronic continuous hypoxia group and a control group. The systolic blood pressure (SBP) was measured with tail-cuff method. RT-PCR was used to examine mRNA expressions of NADPH oxidase subunit gp91phox, p22phox, p47phox. Immunohistochemistry and semiquantitative analysis of NADPH oxidase subunits p22phox were done in the carotid body sections of all rats. Results Compared with normal group [ ( 124 ± 7 ) mm Hg, 1 mm Hg = 0. 133 kPa ] and chronic continuous hvpoxia group[ (129 ± 9) mm Hg], the SBP in CIH group [( 145 ± 11 ) mm Hg] was significantly higher( F = 19. 895, P ＜0. 01 ＝, and the expression of NADPH oxidase subunits gp91phox,p22phox,p47phox mRNA in CIH group ( 2. 82 ± 0. 51, 2. 74 ± 0. 45, 2. 88 ± 0. 47, respectively ) were significantly higher than those in chronic continuous hypoxia group ( 2. 35 ± 0. 42, 2. 25 ± 0. 38, 2. 41 ±0. 43, respectively)and normal group(2. 23 ±0. 35, 2. 16 ±0. 30, 2. 30 ±0. 36, respectively) ( F =5.794,6. 854, 7. 163, respectively, P ＜ 0. 01 ). The Immunohistochemistry and semiquantitative analysis showed that the expression of NADPH oxidase subunit p22phox in the carotid body in CIH group ( 99 ± 12 ) were more than those in chronic continuous hypoxia and control groups ( 38 ± 7 and 34 ± 8, P ＜ 0. 05 ).Conclusion CIH upregulates the expression of NADPH oxidase in rat carotid body and elevates the rat SBP. These results indicate that NADPH oxidase up-expression is closely associated with OSAHS patients with hypertension.