国际呼吸杂志
國際呼吸雜誌
국제호흡잡지
INTERNATIONAL JOURNAL OF RESPIRATION
2015年
13期
988-993
,共6页
韩茜%杨思俊%叶秀文%麦翠和%张挪富
韓茜%楊思俊%葉秀文%麥翠和%張挪富
한천%양사준%협수문%맥취화%장나부
慢性间歇性低氧%阻塞性睡眠呼吸暂停综合征%高脂血症%炎症反应%血红素加氧酶-1
慢性間歇性低氧%阻塞性睡眠呼吸暫停綜閤徵%高脂血癥%炎癥反應%血紅素加氧酶-1
만성간헐성저양%조새성수면호흡잠정종합정%고지혈증%염증반응%혈홍소가양매-1
Chronic intermittent hypoxia%Obstructive sleep apnea syndrome%Hyperlipidemia%Inflammation%Heme oxygenase-1
目的 观察慢性间歇性低氧(CIH)及高脂高胆固醇(HFHC)饮食诱导的高脂血症对大鼠全身及心脏局部炎症反应的影响.方法 Sprague-Dawley雄性大鼠64只,随机分为对照组,慢性间歇低氧组+常规饲料喂养组(CIH组),常氧+HFHC饲料喂养组(IA/HFHC组)和慢性间歇低氧+HFHC饲料喂养组(CIH/HFHC组),每组16只.CIH组大鼠予间歇低氧环境中(4 min 10％+2 min 21％ O2,8 h/d).分别于2周或4周处死大鼠.采用ELISA检测大鼠血清及心脏局部炎症因子的表达水平:中性粒细胞化学趋化因子-1(CINC-1),IL-6,肿瘤坏死因子-α(TNF-α);免疫组织化学法检测大鼠心脏血红素加氧酶1(HO-1)表达水平,Western blot法检测心脏ERK及Akt通路活化.结果 HFHC饲料喂养大鼠导致血清总胆固醇水平升高而CIH未导致胆固醇水平改变[2周:(99.99±3.81) mg/dl vs (26.55±4.33) mg/dl;4周:(121.1±4.59) mg/dl vs (34.14±2.35) mg/dl].CIH及HFHC饮食均可时间依赖性增加血清CINC-1水平(2周:分别为1.4倍和1.9倍;4周:分别为1.9倍和2.4倍),CIH与HFHC有协同作用(2周:基础水平2.3倍;4周:基础水平3.0倍).4周的CIH及HFHC饮食可降低心脏组织炎症因子水平(CINC-1:分别为基础水平0.8和0.9;IL6:均为基础水平0.7;TNFα:均为基础水平0.7),CIH与HFHC对彼此均无协同作用.4周CIH及HFHC饲料喂养可活化ERK与Akt通路,并增加心肌细胞HO-1表达水平,CIH与HFHC对彼此均无协同作用.结论 CIH和高脂血症所致的心脏组织炎症反应可能作为阻塞性睡眠呼吸暂停综合征相关性心血管疾病的致病机制之一;另一方面,通过ERK和Akt活化引起的HO1表达上调可保护心肌免受炎症反应的损害.
目的 觀察慢性間歇性低氧(CIH)及高脂高膽固醇(HFHC)飲食誘導的高脂血癥對大鼠全身及心髒跼部炎癥反應的影響.方法 Sprague-Dawley雄性大鼠64隻,隨機分為對照組,慢性間歇低氧組+常規飼料餵養組(CIH組),常氧+HFHC飼料餵養組(IA/HFHC組)和慢性間歇低氧+HFHC飼料餵養組(CIH/HFHC組),每組16隻.CIH組大鼠予間歇低氧環境中(4 min 10％+2 min 21％ O2,8 h/d).分彆于2週或4週處死大鼠.採用ELISA檢測大鼠血清及心髒跼部炎癥因子的錶達水平:中性粒細胞化學趨化因子-1(CINC-1),IL-6,腫瘤壞死因子-α(TNF-α);免疫組織化學法檢測大鼠心髒血紅素加氧酶1(HO-1)錶達水平,Western blot法檢測心髒ERK及Akt通路活化.結果 HFHC飼料餵養大鼠導緻血清總膽固醇水平升高而CIH未導緻膽固醇水平改變[2週:(99.99±3.81) mg/dl vs (26.55±4.33) mg/dl;4週:(121.1±4.59) mg/dl vs (34.14±2.35) mg/dl].CIH及HFHC飲食均可時間依賴性增加血清CINC-1水平(2週:分彆為1.4倍和1.9倍;4週:分彆為1.9倍和2.4倍),CIH與HFHC有協同作用(2週:基礎水平2.3倍;4週:基礎水平3.0倍).4週的CIH及HFHC飲食可降低心髒組織炎癥因子水平(CINC-1:分彆為基礎水平0.8和0.9;IL6:均為基礎水平0.7;TNFα:均為基礎水平0.7),CIH與HFHC對彼此均無協同作用.4週CIH及HFHC飼料餵養可活化ERK與Akt通路,併增加心肌細胞HO-1錶達水平,CIH與HFHC對彼此均無協同作用.結論 CIH和高脂血癥所緻的心髒組織炎癥反應可能作為阻塞性睡眠呼吸暫停綜閤徵相關性心血管疾病的緻病機製之一;另一方麵,通過ERK和Akt活化引起的HO1錶達上調可保護心肌免受炎癥反應的損害.
목적 관찰만성간헐성저양(CIH)급고지고담고순(HFHC)음식유도적고지혈증대대서전신급심장국부염증반응적영향.방법 Sprague-Dawley웅성대서64지,수궤분위대조조,만성간헐저양조+상규사료위양조(CIH조),상양+HFHC사료위양조(IA/HFHC조)화만성간헐저양+HFHC사료위양조(CIH/HFHC조),매조16지.CIH조대서여간헐저양배경중(4 min 10％+2 min 21％ O2,8 h/d).분별우2주혹4주처사대서.채용ELISA검측대서혈청급심장국부염증인자적표체수평:중성립세포화학추화인자-1(CINC-1),IL-6,종류배사인자-α(TNF-α);면역조직화학법검측대서심장혈홍소가양매1(HO-1)표체수평,Western blot법검측심장ERK급Akt통로활화.결과 HFHC사료위양대서도치혈청총담고순수평승고이CIH미도치담고순수평개변[2주:(99.99±3.81) mg/dl vs (26.55±4.33) mg/dl;4주:(121.1±4.59) mg/dl vs (34.14±2.35) mg/dl].CIH급HFHC음식균가시간의뢰성증가혈청CINC-1수평(2주:분별위1.4배화1.9배;4주:분별위1.9배화2.4배),CIH여HFHC유협동작용(2주:기출수평2.3배;4주:기출수평3.0배).4주적CIH급HFHC음식가강저심장조직염증인자수평(CINC-1:분별위기출수평0.8화0.9;IL6:균위기출수평0.7;TNFα:균위기출수평0.7),CIH여HFHC대피차균무협동작용.4주CIH급HFHC사료위양가활화ERK여Akt통로,병증가심기세포HO-1표체수평,CIH여HFHC대피차균무협동작용.결론 CIH화고지혈증소치적심장조직염증반응가능작위조새성수면호흡잠정종합정상관성심혈관질병적치병궤제지일;령일방면,통과ERK화Akt활화인기적HO1표체상조가보호심기면수염증반응적손해.
Objective Obstructive sleep apnea syndrome (OSAS),with intermittent hypoxia during sleep,is increasingly recognized as an independent risk factor of cardiovascular diseases (CVD).Oxidative stress and inflammation are pathogenic mechanisms in CVD,but majority of studies have focused on the systemic status.The aim of this study was to use an animal model to evaluate oxidative stress and inflammation in response to chronic intermittent hypoxia (CIH) with or without diet-induced hyperlipidemia,with special reference to any difference in the systemic and cardiac response,and the mechanistic pathways involved.Methods Male Sprague-Dawley rats were divided into four groups:regular chow diet or high fat high cholesterol (HFHC) diet plus intermittent air (IA) or IH treatment,and rats were sacrificed at 2 or 4 weeks.Serum and cardiac levels of oxidative and pro-inflammatory markers were assayed with ELISA,the expression of HO-1 was examined by immunohistochemistry and activation of signaling pathways in the heart were analyzed by Western blot.Results IH and HFHC diet alone or together caused time-dependent elevation in serum CINC-1 levels.In contrast,suppression of the cardiac levels of pro-inflammatory markers were seen,accompanied by upregulation of expression of cardiac heam-oxygenase,HO 1,a cytoprotective protein at 4 weeks,when cardiac activations of ERK and Akt were also observed.Conclusions Inflammation resulted from CIH and hyperlipidemia may serve as a potential mechanism underlying OSAS-related CVD.However,the upregulation of HO-1 expression via ERK and Akt activation in cardiac tissues may help to protect the heart from inflammatory insults.
