模拟高原低压低氧环境对大鼠心脏结构和功能影响
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摘要
目的:探讨模拟海拔7 000 m低压低氧环境对大鼠心脏结构和功能的影响。方法:96只雄性SD大鼠随机分为常压常氧对照组(对照组)和高原低压低氧组(低氧组)。低氧组大鼠放置于大型多因素复合环境模拟实验舱内,模拟海拔7 000 m高原环境饲养。实验舱运行时间23 h/d,控制昼夜比大约12 h∶12 h;对照组置于相同条件的常压常氧环境下饲养。低氧组又根据低氧时间不同分为3 d组、7 d组、14 d组和28 d组,同时设置与各低氧组相对应的对照组,每组均12只大鼠。应用超声心动图、心电图、血常规、血生化综合评价高原低压低氧环境下大鼠心脏结构和功能变化,心肌组织HE染色分析心肌组织病理变化。结果:与相同时间点对照组比较(1)随着低压低氧暴露时间延长,大鼠体质量增长明显缓慢,动脉血氧饱和度14 d和28 d显著降低(P<0.05)。(2)低氧组大鼠左心室舒张末期前壁厚度(LVAWD)及左心室舒张末期后壁厚度(LVPWD)于28 d时显著升高(P<0.05)。舒张末期左心室腔直径(LVIDD)及收缩末期左心室腔直径(LVIDS)于28 d时明显降低(P<0.05,P<0.01)。左心室射血分数(EF%)、左室短轴缩短率(FS%)、肺静脉血流峰值速度(PV peak velocity)及肺静脉血流峰梯度(PV peak gradient)于低氧7 d下降明显(P<0.05,P<0.01),低氧14 d及低氧28 d恢复。(3)低氧组大鼠心电图QRS间期与QT间期在14 d及28 d显著延长(P<0.05,P<0.01)。ST段3 d和7 d显著压低(P<0.05,P<0.01)。R波振幅于7 d、14 d及28d显著降低(P<0.05,P<0.01)。(4)低氧各组大鼠红细胞计数(RBC)、血红蛋白(HGB)、红细胞分布宽度(RDW)均明显升高(P<0.01)。血小板计数(PLT)于14 d及28 d明显下降(P<0.01)。血肌酐(CR)于14 d及28 d显著升高(P<0.05)。(5)心肌病理提示,低氧3 d和7 d可见心肌水肿、肌浆凝聚,横纹不清,灶状变性和坏死伴炎性细胞浸润。低氧14 d和28 d心肌组织炎症性病理损伤逐渐减少。心肌细胞逐渐肥大,成纤维细胞逐渐增生。心肌间质胶原纤维逐渐增多等心肌代偿修复性病理变化显著。结论:暴露于模拟海拔7 000 m低压低氧环境下3 d大鼠心功能明显降低,7 d最为显著。
Objective: To investigate the effects of simulated hypobaric hypoxia environment at 7 000 m above sea level on cardiac structure and function in rats. Methods: A total of 96 male SD rats were randomly divided into high-altitude hypobaric hypoxia group( hypoxia group) and normobaric normoxia group( control group). Rats of hypoxia group were placed in a large cabin simulated 7 000 m high-altitude hypobaric hypoxia environment. Operating time 23 h/d,the control circadian ratio of approximately 12 h ∶ 12 h. The rats in control group were bred under normobaric normoxia. The hypoxic group was divided into 3 d,7 d,14 d,28 d groups according to hypoxic time,12 rats in each group. Changes of structure and function of heart due to hypoxia were evaluated by echocardiography and electrocardiogram. Myocardial pathological changes were analyzed by hematoxylin-eosin staining( HE). Results: Compared with the control group at the same time point(1)With prolonged exposure to hypobaric hypoxia,the growth ratio of body mass in rats is slower.Arterial oxygen saturation was significantly lower in both 14 d and 28 d( P<0.05).(2) Left ventricular end-diastolic anterior wall thickness( LVAWD) and left ventricular end-diastolic posterior wall thickness( LVPWD) of rats in 28 d were increased significantly( P<0.05). Left ventricular end-diastolic diameter( LVIDD) and left ventricular internal dimension systole( LVIDS) of rats in 28 d were decreased significantly( P<0.05,P<0.01). Left ventricular ejection fraction( EF),fractional shortening of left ventricle( FS),pulmonary vein( PV) peak velocity and PV peak gradient of rats in 7 d were decreased significantly( P<0.05,P<0.01).(3)The QRS and QT interval period were significantly prolonged in 14 d and 28 d( P<0.05,P<0.01). The ST was significantly lower in 3 d and 7 d( P<0.05,P<0.01). The amplitude of R wave gradually shifted downward in 7 d,14 d,28 d( P<0.05,P<0.01).(4)The red blood cell( RBC),hemoglobin( HGB),red blood cell distribution width( RDW) in hypoxic group were increased significantly( P<0.01). The platelet count( PLT) count was decreased significantly in 14 d and 28 d( P<0.01). The serum creatinine( CR) was increased significantly in 14 d and 28 d( P<0.05).(5)Pathological changes such as myocardial edema,sarcolemma condensate,focal degeneration and necrosis with inflammatory cell infiltration could be found at early stage of hypoxia. Myocardial compensatory repair such as myocardial fibroblasts proliferation was significant at end stage of hypoxia. Conclusion: Left ventricular systolic functions of rats were decreased significantly after exposure to high altitude hypoxia hypobaric. The left ventricular systolic functions would recovery compensatory after one week exposed to high altitude hypoxia hypobaric.
Objective: To investigate the effects of simulated hypobaric hypoxia environment at 7 000 m above sea level on cardiac structure and function in rats. Methods: A total of 96 male SD rats were randomly divided into high-altitude hypobaric hypoxia group( hypoxia group) and normobaric normoxia group( control group). Rats of hypoxia group were placed in a large cabin simulated 7 000 m high-altitude hypobaric hypoxia environment. Operating time 23 h/d,the control circadian ratio of approximately 12 h ∶ 12 h. The rats in control group were bred under normobaric normoxia. The hypoxic group was divided into 3 d,7 d,14 d,28 d groups according to hypoxic time,12 rats in each group. Changes of structure and function of heart due to hypoxia were evaluated by echocardiography and electrocardiogram. Myocardial pathological changes were analyzed by hematoxylin-eosin staining( HE). Results: Compared with the control group at the same time point(1)With prolonged exposure to hypobaric hypoxia,the growth ratio of body mass in rats is slower.Arterial oxygen saturation was significantly lower in both 14 d and 28 d( P<0.05).(2) Left ventricular end-diastolic anterior wall thickness( LVAWD) and left ventricular end-diastolic posterior wall thickness( LVPWD) of rats in 28 d were increased significantly( P<0.05). Left ventricular end-diastolic diameter( LVIDD) and left ventricular internal dimension systole( LVIDS) of rats in 28 d were decreased significantly( P<0.05,P<0.01). Left ventricular ejection fraction( EF),fractional shortening of left ventricle( FS),pulmonary vein( PV) peak velocity and PV peak gradient of rats in 7 d were decreased significantly( P<0.05,P<0.01).(3)The QRS and QT interval period were significantly prolonged in 14 d and 28 d( P<0.05,P<0.01). The ST was significantly lower in 3 d and 7 d( P<0.05,P<0.01). The amplitude of R wave gradually shifted downward in 7 d,14 d,28 d( P<0.05,P<0.01).(4)The red blood cell( RBC),hemoglobin( HGB),red blood cell distribution width( RDW) in hypoxic group were increased significantly( P<0.01). The platelet count( PLT) count was decreased significantly in 14 d and 28 d( P<0.01). The serum creatinine( CR) was increased significantly in 14 d and 28 d( P<0.05).(5)Pathological changes such as myocardial edema,sarcolemma condensate,focal degeneration and necrosis with inflammatory cell infiltration could be found at early stage of hypoxia. Myocardial compensatory repair such as myocardial fibroblasts proliferation was significant at end stage of hypoxia. Conclusion: Left ventricular systolic functions of rats were decreased significantly after exposure to high altitude hypoxia hypobaric. The left ventricular systolic functions would recovery compensatory after one week exposed to high altitude hypoxia hypobaric.
引文
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[10]郭郑昊,黄付敏,陆慧,等.不同海拔高度对健康成年男性心脏血流动力学和心电图的影响[J].中国应用生理学杂志,2012,28(1):1-4.
[11]Caravita S,Faini A,Bilo G,et al.Ischemic changes in exercise ECG in a hypertensive subject acutely exposed to high altitude.Possible role of a high-altitude induced imbalance in myocardial oxygen supply-demand[J].Int J Cardiol,2014,171(3):e100-102.
[12]Nepal O,Pokharel BR,Khanal K,et al.Relationship between arterial oxygen saturation and hematocrit,and effect of slow deep breathing on oxygen saturation in Himalayan high altitude populations[J].Kathmandu Univ Med J(KUMJ),2012,10(39):30-34.
[2]Meier D,Collet TH,Locatelli I,et al.Does this patient have acute mountain sickness?:The rational clinical examination systematic review[J].JAMA,2017,318(18):1810-1819.
[3]Llanos AJ,Ebensperger G,Herrera EA,et al.The heme oxygenase-carbon monoxide system in the regulation of cardiorespiratory function at high altitude[J].Respir Physiol Neurobiol,2012,184(2):186-191.
[4]Singh M,Shukla D,Thomas P,et al.Hypoxic preconditioning facilitates acclimatization to hypobaric hypoxia in rat heart[J].J Pharm Pharmacol,2010,62(12):1729-1739.
[5]王延玲,王荣,杨锁泉,等.急进不同低海拔环境对大鼠心肌的影响[J].南方医科大学学报,2014,34(3):312-316.
[6]Huang HH,Tseng CY,Fan JS,et al.Alternations of heart rate variability at lower altitude in the predication of trekkers with acute mountain sickness at high altitude[J].Clin J Sport Med,2010,20(1):58-63.
[7]饶明月,覃军,高旭滨,等.急性高原暴露后左心功能变化及与急性高原病的关系[J].中国应用生理学杂志,2014,30(3):223-226.
[8]Rao M,Li J,Qin J,et al.Left ventricular function during acute high-altitude exposure in a large group of healthy young Chinese men[J].PLo S One,2015,10(1):e0116936.
[9]Oikawa M,Wu M,Lim S.et al.Cyclic nucleotide phosphodiesterase 3A1 protects the heart against ischemiareperfusion injury[J].J Mol Cell Cardiol,2013,64:11-19.
[10]郭郑昊,黄付敏,陆慧,等.不同海拔高度对健康成年男性心脏血流动力学和心电图的影响[J].中国应用生理学杂志,2012,28(1):1-4.
[11]Caravita S,Faini A,Bilo G,et al.Ischemic changes in exercise ECG in a hypertensive subject acutely exposed to high altitude.Possible role of a high-altitude induced imbalance in myocardial oxygen supply-demand[J].Int J Cardiol,2014,171(3):e100-102.
[12]Nepal O,Pokharel BR,Khanal K,et al.Relationship between arterial oxygen saturation and hematocrit,and effect of slow deep breathing on oxygen saturation in Himalayan high altitude populations[J].Kathmandu Univ Med J(KUMJ),2012,10(39):30-34.