抗氧化剂对慢性间歇性乏氧所致小鼠心肌重构的保护作用  

Protective effects of antioxidants on chronic intermittent hypoxia-induced cardiac remodeling in mice

作　　者：尹霞[1] 李柏成[2] 赵宇光[3] 孙伟霞[4] 郑杨[1] 

机构地区：[1]吉林大学第一医院心血管疾病诊疗中心,长春130021 [2]吉林省肿瘤医院体检中心 [3]吉林大学第一医院肿瘤中心,长春130021 [4]吉林大学第一医院肾病中心,长春130021

出　　处：《中华心血管病杂志》2014年第11期944-950,共7页Chinese Journal of Cardiology

摘　　要：目的 探讨慢性间歇性乏氧（chronic intermittent hypoxia,CIH）所致心肌重构的病理机制,并观察两种抗氧化剂对CIH所致心肌重构的保护作用.方法 FVB小鼠,雄性,8- 10周龄,随机数字法分为对照组、CIH组、APO组、CIH＋ APO组、SOD组和CIH＋ SOD组,共6组,每组5只小鼠.CIH处理方案为20.9％O2与8％O2吸入氧浓度分数（FIO2）交替进行,30次/h,12 h/d,最低氧饱和度变化维持在60％ - 70％,持续20 s.APO组予以腹腔注射夹竹桃毒素3 mg·kg^-1·d^-1,SOD组予以腹腔注射MnTMPyP 5 mg · kg^-1·d^-1.CIH处理4周后,应用超声心动图测定小鼠心脏结构及其功能,应用分子生物学技术及生物化学方法检测心肌组织炎症反应、凋亡、纤维化及心肌组织丙二醛（MDA）含量.结果 （1）CIH可诱导心肌重构：干预4周后,CIH组小鼠体质量与对照组比较差异无统计学意义,但心脏质量大于对照组（P＜0.05）.CIH组与对照组小鼠组间舒张期室间隔厚度、收缩期室间隔厚度、舒张期左心室后壁厚度及收缩期左心室后壁厚度差异无统计学意义,但CIH组LVIDd及LVIDs大于对照组（P均＜0.05）,且左心室射血分数及左心室短轴缩短率低于对照组（P均＜0.05）.CIH组小鼠心房利钠肽（ANP）的蛋白表达水平高于对照组（P＜0.05）.（2）CIH可诱导心肌组织炎性反应和纤维化：CIH组小鼠心肌组织炎性细胞浸润及炎性标志物血管细胞黏附分子-1（VCAM-1）蛋白表达水平高于对照组,心肌MDA含量亦高于对照组（P均＜0.05）.CIH组小鼠可检测到凋亡的心肌细胞,且凋亡标志物CIEBP同源蛋白（CHOP）表达水平高于对照组（P＜0.05）.天狼星红染色显示CIH组小鼠心肌组织有胶原沉积明显,且心肌纤维化相关指标结缔组织生长因子（CTGF）和血纤维蛋白溶酶原激活物抵制剂-1（PAI-1）的表达水平均高于对照组（P＜0.05）.（3）抗氧化剂治疗可抑制CIH诱导的心肌损伤：APO组与CIObjective Chronic intermittent hypoxia （CIH）animal model was used to mimic the status of obstructive sleep apnea （OSA） in order to investigate the pathological mechanism of CIH-induced cardiac remodeling and observe the protective effect of antioxidants.Methods FVB mice （8-10 weeksold） were randomly divided into control （saline,i.p.） group and CIH group,reduced form of nicotinamide adenine dinucleotide phosphate oxidase inhibitor,apocynin （APO,3 mg · kg^-1 · d^-1,i.p.） alone or CIH＋APO,SOD mimic MnTMPyP （SODM,5 mg · kg^-1 d^-1,i.p.） alone or CIH ＋ SODM （n =5 each）.After 4 weeks,cardiac function and structure were determined by echocardiography,cardiac inflammation,apoptosis,cardiac fibrosis and cardiac MDA contents were examined by Western blot and chemical-biological methods,respectively.Results （1） Heart weight,LVIDd and LVIDs were increased while LYEF and FS were reduced in CIH group compared to control group （all P 〈 0.05）.（2） Myocardial protein expression of ANP and VCAM-1 was significantly upregulated,myocardial MDA content and apoptosis as well as myocardial fibrosis marker CTGF and PAI-1 were increased in CIH group compared to control group （all P 〈 0.05）.（3） Above parameters were similar between APO and CIH ＋ APO as well as SODM and CIH ＋ SODM （all P 〉 0.05）.Conclusion CIH could induce cardiac remodeling and CIH-induced cardiac inflammation,cardiac oxidative injury,cardiac apoptosis and cardiac fibrosis serve as the pathological mechanisms of CIH-induced cardiac remodeling.The protective effects of the two antioxidants suggest that the main mechanism of CIH-induced cardiac injury is oxidative stress.

关 键 词：睡眠呼吸暂停 阻塞性 心室重构 抗氧化剂 缺氧 

分 类 号：R766[医药卫生—耳鼻咽喉科]