CAJ | 학술논문

目的研究慢性间歇低氧(CIH)与持续低氧(CH)对大鼠血清及组织器官局部的肾素血管紧张素(RAS)系统的影响,以探讨CIH相关性高血压及低氧性肺动脉高压的发生机制.方法 18只SD雄性大鼠按随机数字表法分为CIH组、CH组和对照组共3组,每组6只.CIH组大鼠循环给予氮气和压缩空气(每循环180 s,舱内最低氧浓度达6％～8％,维持20～25 s,然后恢复至21％,7 h/d),CH组持续给予氮气(舱内氧浓度保持8％～12％,7 h/d),对照组大鼠常规饲养.结果第6周时CIH大鼠收缩压(SBP)显著高于CH组、对照组(P＜0.05)和实验前水平(P＜0.01).CIH分别与CH和对照组比较:肾小动脉和肺小动脉中ACE及ACE2水平差异有统计学意义(P＜0.05)；血清和肾组织中AngⅡ显著增高(P＜0.05),Ang-(1-7)则明显降低(P＜0.05).CH组肺组织AngⅡ较CIH及对照组增高(P＜0.05),Ang-(1-7)降低(P ＜0.05)；SBP与血清及肾AngⅡ水平呈正相关；与Ans-( 1-7)水平呈负相关.CIH组肾小动脉及CH组肺小动脉管壁厚度、壁厚度占外径或内径的百分比(WT％)及管壁面积占血管壁总面积的百分比(WA％)分别与其他两组比较均有明显差异(P＜0.05).肺及肾的小动脉管壁厚度与其相应组织局部的AngⅡ呈正相关(r=0.386、0.414,均P＜0.05),与Ang-( 1-7)呈负相关(r=-0.401,-0.394,均P＜0.05).结论 CIH与CH两种低氧方式对大鼠血清及各组织局部的RAS系统影响程度及结果存在差异性,CIH主要影响大鼠肾组织及肾小动脉及体循环RAS系统,与血压增高密切相关；CH主要影响肺组织及肺小动脉RAS系统,可能与肺动脉重塑及肺动脉高压有关.
목적 연구만성간헐저양(CIH)여지속저양(CH)대대서혈청급조직기관국부적신소혈관긴장소(RAS)계통적영향,이탐토CIH상관성고혈압급저양성폐동맥고압적발생궤제.방법 18지SD웅성대서안수궤수자표법분위CIH조、CH조화대조조공3조,매조6지.CIH조대서순배급여담기화압축공기(매순배180 s,창내최저양농도체6％～8％,유지20～25 s,연후회복지21％,7 h/d),CH조지속급여담기(창내양농도보지8％～12％,7 h/d),대조조대서상규사양.결과 제6주시CIH대서수축압(SBP)현저고우CH조、대조조(P＜0.05)화실험전수평(P＜0.01).CIH분별여CH화대조조비교:신소동맥화폐소동맥중ACE급ACE2수평차이유통계학의의(P＜0.05)；혈청화신조직중AngⅡ현저증고(P＜0.05),Ang-(1-7)칙명현강저(P＜0.05).CH조폐조직AngⅡ교CIH급대조조증고(P＜0.05),Ang-(1-7)강저(P ＜0.05)；SBP여혈청급신AngⅡ수평정정상관；여Ans-( 1-7)수평정부상관.CIH조신소동맥급CH조폐소동맥관벽후도、벽후도점외경혹내경적백분비(WT％)급관벽면적점혈관벽총면적적백분비(WA％)분별여기타량조비교균유명현차이(P＜0.05).폐급신적소동맥관벽후도여기상응조직국부적AngⅡ정정상관(r=0.386、0.414,균P＜0.05),여Ang-( 1-7)정부상관(r=-0.401,-0.394,균P＜0.05).결론 CIH여CH량충저양방식대대서혈청급각조직국부적RAS계통영향정도급결과존재차이성,CIH주요영향대서신조직급신소동맥급체순배RAS계통,여혈압증고밀절상관；CH주요영향폐조직급폐소동맥RAS계통,가능여폐동맥중소급폐동맥고압유관.
Objective To Investigate the influences of chronic intermittent hypoxia (CIH) and continuous hypoxia (CH) on renin angiotensin system (RAS) in serum and tissues of rats,and therefore to investigate the mechanism of CIH-induced hypertension and hypoxia induced pulmonary hypertension.Methods Eighteen male Sprague-Dawley(SD) rats were divided into 3 groups: CIH group,CH group and control group(UC).CIH rats were subjected to alternating cycles of hypoxia (6％～8％ O2 in N2 for 20 ～25 s) and normoxia (21％ O2 in N2 for 2 min) every 180 s for 7 h/d.CH rats were consistently given nitrogen (oxygen concentration 8％ - 12％ in the cabin,7 h/d) ,while the UC rats were not treated.Results Systolic blood pressure (SBP) in the CIH rats at the end of 6th week was significantly elevated compared with baseline SBP (P ＜ 0.001 ),and that in the CH and the UC rats ( P ＜ 0.05 ).At the end of 6th week,the expression of ACE and ACE2 in the renal arteriole was significantly different(P ＜0.05),and the levels of Ang Ⅱ in serum and kidney tissues were increased.Ang-(1-7) was decreased in the CIH rats compared with the CH and the UC rats ( P ＜ 0.05 ).The levels of Ang Ⅱ in pulmonary tissues were increased,while the levels of Ang-(1-7) were decreased in the CH rats compared with the CIH and the UC rats ( P ＜ 0.05 ).SBP showed a positive correlation with Ang Ⅱ in serum and kidney tissues,and a negative correlation with Ang-(1-7) in serum and kidney tissues.There were significant differences in arterial wall thickness,WT％,and WA％ of renal arterioles and pulmonary arterioles among the 3 groups. Wall thickness of pulmonary arterioles and kidney arterioles was positively correlated with Ang Ⅱ in pulmonary and kidney tissues ( r =0.386,0.414,P ＜ 0.05 ),and negatively correlated with Ang-( 1-7 ) ( r =- 0.401,-0.394,P ＜ 0.05 ).Conclusion CIH and CH showed different effects on RAS in the serum and the tissues of rats.CIH mainly affected levels of RAS in the serum,kidney tissues and renal arterioles,and was closely related with blood pressure. CH mainly affected the levels of RAS in lung tissues and pulmonary small arteries,which may be related with pulmonary,hypertension and pulmonary arterial remodeling.