慢性间歇性低压低氧对大鼠动脉血管收缩功能的影响

本研究旨在探讨慢性间歇性低压低氧(chronicintermittent hypobaric hypoxia,CIHH)对大鼠胸主动脉和肺动脉收缩功能的影响及其机制.雄性Sprague-Dawley大鼠随机分为4组:CIHH处理14天组(CIHH 14)、28天组(CIHH 28)、42天组(CIHH 42)和对照组(...     

黄连对正常氧和慢性间歇性低压低氧大鼠离体胸主动脉收缩活动的影响

目的：观察黄连对正常氧和慢性间歇性低压低氧（CIHH）大鼠离体胸主动脉收缩活动的影响并探讨其作用机制。方法：取青年雄性SD大鼠,随机分为正常氧组和CIHH组。前者不予任何处理,后者于低压氧舱接受28d模拟海拔5000m高度的低压低氧（PB=404mmHg,PO2=84mmHg,11．1％O2）处理,每天6h。制备大鼠离体胸主动脉环并将其恒温灌流,记录黄连对动脉环收缩活动的影响并研究其作用机制。结果：黄连使去甲肾上腺素（NE）和氯化钾（KCl）诱发的正常氧和CIHH大鼠离体动脉环收缩活动明显减弱,但其对两组大鼠动脉收缩的抑制作用无明显差异。除去内皮后各组收缩幅度均无显著变化。以收缩幅度为指标,用Logit法计算正常氧组黄连对NE和KCl诱发收缩的ICso分别为2．99g／L和6．14g／L,CIHH组则分别为3．45g／L和5．81g／L。格列苯脲、左旋硝基精氨酸甲酯可部分阻断黄连对两组大鼠动脉环收缩活动的抑制作用,吲哚美辛还能抑制黄连对正常氧大鼠动脉的舒张作用。黄连明显抑制NE诱发的两组血管细胞内钙性和细胞外钙性收缩。结论：黄连对正常氧和CIHH大鼠离体胸主动脉环具有明显舒张作用,该作用不依赖血管内皮,且在两组之间无显著差异。其抑制CIHH大鼠血管收缩的机制可能是通过激活ATP敏感型钾通道,增加一氧化氮浓度,抑制肌浆网释放Ca2＋及细胞外Ca2＋内流;对正常氧大鼠动脉的舒张作用可能还通过增加局部前列环素。     

姜黄素预处理通过保护线粒体和抗氧化应激减轻干热环境热射病大鼠肝损伤

目的:研究姜黄素预处理对干热环境热射病大鼠肝脏的保护作用及机制。方法:将50只SD大鼠随机分为5组(n=10):常温对照组(Control),干热对照组(HS),50-cur组,100-cur组和200-cur组。Control组、HS组给予生理盐水灌胃,50-cur组、100-cur组、200-cur组分别给予50 mg/kg、100 mg/kg、200 mg/kg浓度的姜黄素灌胃,每天1次,连续7天。第8天除Control组外,其余4组大鼠转移至西北特殊环境人工实验舱(环境温度41±0.5℃,湿度10±1%)进行实验。实验的第150分钟,检测肛温,麻醉后取材。同时Control组直接检测肛温并麻醉取材。检测血清谷丙转氨酶(ALT)、谷草转氨酶(AST)、肝组织丙二醛(MDA)、超氧化物歧化酶(SOD)、过氧化氢酶(CAT)的含量和细胞色素C(Cyt-c)的表达情况。电镜观察肝细胞超微结构的变化。结果:(1)第150分钟,各组大鼠体温均超过42℃,达到热射病状态。姜黄素预处理组体温较HS组降低(P0.01)。姜黄素预处理组组间差异无统计学意义(P0.05)。(2)HS组ALT、AST水平较Control组升高(P0.01)。姜黄素预处理组ALT、AST水平较HS组降低(P0.05),姜黄素预处理组组间差异有统计学意义(P0.05)。(3)HS组与Control组相比MDA水平升高,SOD、CAT水平降低(P0.01)。姜黄素预处理组与HS组相比MDA水平降低,SOD、CAT水平升高(P0.01),姜黄素预处理组组间差异有统计学意义(P0.05)。(4)电镜下,HS组肝细胞内线粒体增生肿胀,嵴结构紊乱、破坏,部分肝细胞核结构破坏;姜黄素预处理组肝细胞内线粒体增生为主,无嵴结构破坏和胞核的改变。(5)HS组肝细胞质内Cyt-c表达(1.29±0.19)较Control组(0.24±0.02)明显增多(P0.01)。姜黄素预处理组Cyt-c表达(50-cur、100-cur、200-cur分别为0.75±0.08、0.64±0.08、0.48±0.06)较HS组相对减低(P0.05),姜黄素预处理组组间差异有统计学意义(P0.05)。结论:干热环境热射病大鼠肝脏损伤明显,姜黄素预处理能减轻干热环境热射病导致的肝损伤,其机制可能与保护线粒体和抗氧化应激有关。姜黄素对热射病大鼠肝脏的保护作用具有剂量依赖性。     

姜黄素预处理对沙漠干热环境热射病大鼠肺损伤及HMGB-1和ICAM-1 mRNA的影响

目的:研究姜黄素预处理对干热环境热射病大鼠肺损伤的保护作用及可能机制。方法:将50只SD大鼠随机分为5组(n=10):常温对照组(NC)、干热对照组(DHC)、低剂量姜黄素预处理组(50 mg/kg),中剂量姜黄素预处理组(100 mg/kg)及高剂量姜黄素预处理组(200 mg/kg)。NC、DHC组给予生理盐水灌胃,姜黄素预处理组给予不同剂量的姜黄素灌胃,每天1次,连续7天。第8天除NC组外,其余4组大鼠转移至西北特殊环境人工实验舱内进行实验,环境温度(41±0.5)℃,湿度(10±1)%。实验的第150分钟达到热射病状态,麻醉后取材。大鼠肺组织通过HE染色并进行肺损伤病理学评分,并应用RT-PCR检测肺组织HMGB1 mRNA和ICAM-1 mRNA的表达。结果:干热对照组大鼠肺组织病理评分、肺组织HMGB1和ICAM-1 mRNA表达较常温对照组、中、高剂量姜黄素预处理组均显著升高(P0.01),高剂量姜黄素预处理组大鼠肺组织病理评分明显低于低、中剂量姜黄素预处理组(P0.01),肺组织HMGB1和ICAM-1 mRNA表达在高剂量姜黄素预处理组明显低于低剂量姜黄素预处理组(P0.01)。肺组织HMGB1和ICAM-1 mRNA的表达均与肺损伤评分具有显著正相关性(r=0.629、0.689,P0.01),HMGB1 mRNA和ICAM-1 mRNA之间的表达也呈显著正相关性(r=0.437,P0.01)。结论:姜黄素可能部分通过抑制HMGB1表达的上调,减少下游的ICAM-1的表达来减轻炎症反应,从而发挥肺损伤保护作用。     

电针预处理促进缺血再灌注后GSK-3β磷酸化诱导脑缺血耐受效应

目的:探索糖原合成激酶3β(GSK-3β)在电针预处理诱导的脑缺血再灌损伤保护中的作用.方法:60只雄性SD大鼠随机分成5组(n=12):假手术(Sham)、大脑中动脉栓塞组(MCAO)、电针预处理组(EA)、电针预处理加LY294002组(EA+LY)、电针预处理加溶剂组(vehicle);通过梗死面积及Garcia评分评价脑损伤程度,通过Western Blot检测GSK-3β活性.结果:与MCAO组相比,EA组梗死容积减少,Garcia评分改善(P＜0.05);与vehicle组相比,EA+LY组梗死容积增加,Garcia评分降低(P＜0.05);与MCAO组相比再灌注后2小时EA组GSK-3β磷酸化水平升高(P＜0.05);与EA组相比EA+LY组GSK-3β3磷酸化水平降低(P＜0.05).结论:电针预处理通过促进缺血再灌注后GSK-3β的磷酸化发挥脑保护作用.     

缺氧预处理对神经干细胞间隙连接蛋白的表达及半通道功能的影响

目的:检测缺氧预处理对神经干细胞间隙连接蛋白的表达情况及半通道功能的影响,为探究缺氧预处理后神经干细胞间细胞通讯提供理论依据。方法:采用免疫组织化学方法检测对照组及缺氧预处理1小时组、缺氧预处理4小时组、缺氧预处理8小时组、缺氧预处理12小时组神经干细胞中cx43、cx36、cx47的表达情况。通过激光共聚焦激光扫描显微镜测量钙黄绿素滤过情况以评估半通道功能的变化。结果:与对照组(1.03±0.14%)比较,在0.5%氧气条件下暴露8小时(3.05±0.40%)和12小时(5.51±0.31%)的神经干细胞坏死率较显著升高(P0.05)。与对照组相比,缺氧预处理4、8、12小时组神经干细胞中cx43、cx36、cx47的表达显著增加,且随着缺氧预处理时间的延长而显著增加(P0.05)。与对照组及加入半通道阻滞剂组相比,缺氧预处理组半通道滤过功能显著增强(P0.05)。结论:缺氧预处理可以以时间依赖性方式提高神经干细胞间隙连接蛋白的表达和半通道滤过功能。神经干细胞暴露于低氧环境而不引起坏死显著增加的最佳时间为4小时。     

镁预处理对兔全脑缺血神经保护作用的实验研究

目的探讨硫酸镁预处理对兔全脑缺血神经保护作用及其机制.方法 45只兔随机分为3组:对照组(n=15)、缺血组(n=15)和镁预处理组(n=15).阻断血管,诱导全脑缺血,缺血时间为 6 min.测定缺血再灌注30 min 兔海马谷氨酸、天冬氨酸、γ-氨基丁酸和甘氨酸含量.检测缺血再灌注3 d 海马CA1区神经元密度和凋亡神经元密度.结果 (1)镁预处理组海马天冬氨酸和甘氨酸显著低于缺血组(P<0.01),而γ-氨基丁酸含量显著高于缺血组(P<0.05);(2)镁预处理组正常神经元密度显著高于缺血组 (P<0.01),缺血神经元密度显著低于缺血组(P<0.01);(3)镁预处理组凋亡神经元密度显著低于缺血组(P<0.01).结论 (1)硫酸镁预处理对兔全脑缺血有神经保护作用;(2)该保护作用的机制可能有:1)抑制兔全脑缺血再灌注30 min 海马天冬氨酸和甘氨酸的过度释放以及抑制γ-氨基丁酸的耗竭;2)抑制兔全脑缺血再灌注3 d 海马CA1区神经元凋亡.     

高压氧预处理对SPS暴露大鼠学习记忆能力以及海马神经元凋亡的影响

目的:研究高压氧(HBO)预处理对SPS暴露大学学习记忆能力及其大脑海马神经元细胞凋亡的影响.方法:48只雄性Sprague-Dawley大鼠(体重220-260 g)随机分为4组(n=12):对照(sham)组,高压氧(HBO)组,SPS组以及高压氧+SPS组.高压氧组每天1小时高压氧预处理(2.5个大气压,100%O2)连续5天;SPS组采用单次延长应激模型;高压氧+SPS组每天l小时高压氧预处理连续5天于最后一次预处理后24小时,制作SPS模型.4组大鼠于SPS暴露后72小时进行TUNEL染色,第15天经行水迷宫测试.结果:水迷宫实验中大鼠逃避潜伏期及游泳路径四组之间有明显统计差异[F0.01(3,28)=4.88＞4.57,P＜0.01;F0.01(3,28)=5.31＞4.57,P＜0.01].SPS组明显长于Sham组(P＜0.01),而高压氧预处理能够逆转这种效应(P＜0.01).游泳速度四组之间无明显统计差异[F0.05(3,28)=2.23＜2.95,P＞0.05]. SPS暴露后海马神经元细胞数量和密度明显减少,给予高压氧预处理后,神经元形态明显好转,但仍不及对照组.结论:高压氧预处理可以减少海马神经元细胞凋亡从而改善SPS暴露后大鼠认知功能障碍.     

姜黄素预处理对沙漠干热环境猪腹部枪弹伤模型生存时间的影响

目的:探讨姜黄素预处理对沙漠干热环境腹部枪弹伤动物模型生存时间的影响。方法:将24头长白仔猪随机分为2组(n=12):姜黄素预处理组和对照组。姜黄素预处理组给予长白仔猪姜黄素100 mg/kg拌料饲养,每天1次,连续7天,对照组给予常规饲料喂养。第8天,将两组猪放入西北特殊环境人工实验舱内,设置环境温度(40.5±0.5)℃,相对湿度(10±2)%,禁食水,放置3小时后建立腹部枪弹伤模型,模型成功后继续放在沙漠干热环境中,每10分钟检测体温变化,并计算长白仔猪的存活时间。结果:姜黄素预处理组平均存活时间为(85.27±2.39)min,对照组的动物模型平均生存时间为(60.10±3.25)min,姜黄素预处理组的生存时间平均比对照组延长约25 min,两组的Kaplan-Meier生存曲线经Log Rank检验具有显著性差异(P0.01)。建立腹部枪弹伤模型后,在相应时间点,姜黄素预处理组的体温明显低于未处理组(P0.01),姜黄素预处理组70 min时的体温与对照组50 min体温比较差异无统计学意义(P0.05)。结论:姜黄素预处理可明显提高干热环境下猪腹部枪弹伤模型的生存时间,体温升高可能是反映干热环境腹部枪弹伤后病程进展的重要指标。     

建立小鼠淋巴瘤模型所需环磷酰胺最佳预处理剂量探索

目的:探讨不同剂量环磷酰胺对小鼠肿瘤成模情况的影响,寻找一种简单、有效的建立肿瘤模型的预处理方法。方法:给予BALB/c裸鼠腹腔注射不同剂量环磷酰胺,72小时后再给予小鼠皮下接种淋巴瘤细胞,观察预处理前后小鼠外周血白细胞数量及体重变化情况,以及肿瘤成模率、急性死亡率等。结果:①组1(NS对照组)、组2(100mg/kg×1d)、组3(125mg/kg×1d)、组4(75mg/kg×2d)预处理后体重较处理前无显著性变化,亦无急性死亡情况发生;而组5(125mg/kg×2d)、组6(200mg/kg×2d)、组7(125mg/kg×3d)、组8(250mg/kg×3d)小鼠体重较预处理前明显减轻,且急性死亡率依次为30%、58.3%、50%、75%;②组1和组2小鼠预处理后72小时外周血白细胞数较处理前无明显差异,同时均未成模;而组3、组4、组5、组6、组7、组8小鼠白细胞较预处理前均显著下降,成模率依次为20%、83.3%、60%、33.3%、50%、25%。结论:使用环磷酰胺75mg/kg连续2天腹腔注射的预处理方案,操作简单,成本低廉,通过观察外周血白细胞数和小鼠体重水平等指标即可初步判断建模情况,同时肿瘤成模率高,毒副作用小,是理想的预处理方案。     

间歇性低压低氧对过氧化氢心肌细胞损伤的保护作用

目的:观察慢性间歇性低压低氧对过氧化氢所致心肌细胞损伤的保护作用及其机制。方法:雄性豚鼠20只,随机分为两组(n=10):对照组(non-IHH)、低氧组(IHH)。低氧组豚鼠于低压氧舱接受28 d(海拔5 000 m、每天6 h)的低压低氧处理。胶原酶方法急性分离心肌细胞。细胞动缘探测系统测定过氧化氢对各组细胞收缩力的变化。生化方法测定各组丙二醛(MDA)、乳酸脱氢酶(LDH)及超氧化物歧化酶(SOD)和过氧化氢酶(CAT)的变化。结果:①过氧化氢可使心肌细胞出现收缩、舒张紊乱,但IHH处理使其出现的潜伏期明显延长。②给予过氧化氢(300μmol/L,10 min)使来自于non-IHH或IHH的心肌细胞LDH、MDA含量均明显增加,但IHH心肌细胞LDH、MDA含量明显低于non-IHH心肌细胞的LDH、MDA含量。③经IHH处理组的心肌细胞SOD,CAT活性均明显高于non-IHH组。给予过氧化氢使来自于non-IHH或IHH的心肌细胞SOD,CAT活性均明显降低,但IHH心肌细胞SOD,CAT活性明显高于non-IHH心肌细胞的SOD,CAT活性。结论:IHH具有对抗过氧化氢心肌细胞损伤的作用,可能与其增强抗氧化酶活性有关。     

Facilitation of chronic intermittent hypobaric hypoxia on carotid sinus baroreflex in anesthetized rats

Our previous study showed that chronic intermittent hypobaric hypoxia (CIHH) could prevent decreases in systemic arterial blood pressure (SABP) during acute hypoxia. However, the mechanism was not clear. The purpose of the present study was to observe whether the carotid sinus baroreflex (CSB) was involved in the antagonizing effect of CIHH on SABP decrease induced by acute hypoxia and to explore the underlying mechanism using perfusion technique in rat isolated carotid sinus area. After 14-day and 28-day CIHH exposure, the CSB in rats was enhanced markedly, manifesting as increases in PS and RD, and decreases in TP and SP. This facilitation of CSB was partly abolished by Glibenclamide (Gli, 10 μM), a K ATP channel blocker, but was not influenced by L-NAME (100 μM), a nitric oxide synthase (NOS) inhibitor. The results of the study suggested that CIHH facilitated CSB through opening the K ATP channels in carotid sinus of anesthetic rats and might be one of mechanisms of CIHH keeping SABP homeostasis during acute hypoxia.     

Preservation of TSPO by chronic intermittent hypobaric hypoxia confers antiarrhythmic activity

Abnormal activation of mitochondrial translocator protein (TSPO) contributes to arrhythmogenesis during cardiac metabolic compromise; however, its role in the antiarrhythmic activities of chronic hypoxia adaptation remains unclear. Our results demonstrated that 80% of normoxic rats developed ischaemic VF, whereas this condition was seldom observed in rats with 14 days of chronic intermittent hypobaric hypoxia (CIHH). TSPO stimulation or inhibition affected the arrhythmias incidence in normoxic rats, but did not change the CIHH‐mediated antiarrhythmic effects. Abrupt and excessive elevation of TSPO activity was positively linked to ischaemic VF, and CIHH preserved TSPO activity during ischaemia. The preservation of TSPO activity by CIHH also contributed to the maintenance of intracellular Ca homeostasis. These results suggest that the blunt sensitivity of TSPO to ischaemic stress may be responsible for the antiarrhythmic effects by CIHH.     

间歇性低压低氧与连续性低压低氧对大鼠血液动力学作用的比较(英文)

本研究旨在探讨并比较慢性间歇性低压低氧（intermitten thypobaric hypoxia,IHH）和慢性连续性低压低氧（continuous hypobaric hypoxia,CHH）对大鼠血液动力学作用的影响。40只成年Sprague—Dawley大鼠随机分为5组：对照组（CON）,28天IHH处理组（IHH28）,42天IHH处理组（IHH42）,28天CHH组（CHH28）和42天CHH组（CHH42）。IHH火鼠于低压氧舱分别接受28或42天模拟5000m海拔高度低氧（11．1％O2）处理、每天6h。CHH处理大鼠生活在低压氧舱环境中,除每天半小时常氧供食、供水和清洁外,其余时间均分别接受时程为28或42天的模拟5000m海拔高度低氧（11．1％O2）处理。每周定时测定大鼠体重。通过导管法测定基础常氧和急性低氧状态下的血液动力学,包括半均动脉压（meanartery blood pressure,MAP）、心率（heartrate,HR）、左审收缩峰压（1eft ventricular systolic pressure,LVSP）、正负左率最人压力变化速率（maximum change rate of left ventricular pressure,&#177;LVdP／dtmax）。通过生物化学方法测定大鼠心肌超氧化物岐化酶活性和丙二醛含量。并分别测定全心、左心室和右心室重量。结果显示：（1）CHH42大鼠基础HR和MAP低于CON,IHH和CHH28大鼠（P〈0．05）。（2）IHH大鼠表现出明显的抗心肌缺氧／复氧损伤作用,表现为急性低氧状态下的HR、MAP、LVSP和＋LVdP/dtmax,改变明显低于CON大鼠（P〈0．05）;CHH大鼠表现出更为明显的抗急性低氧心脏保护作用,表现为急性低氧的HR、MAP、LVSP和&#177;LVdP/dtmax;改变明显低于CON和IHH火鼠（P〈0．05）,但出现复氧损伤作用,表现为复氧过程中血液动力学的恢复明显低于CON和IHH大鼠（P〈0．05）。（3）与CON大鼠相比较,IHH和CHH大鼠心肌抗氧化能力明显增强（P〈0．05,P〈0．01）。（4）与IHH和CON大鼠相比较,CHH大鼠表现明显的右心室肥厚（P〈0．01）。结果表明,IHH可诱导有效的心脏保护作用,而无明显的不良反应,因而具有潜在的实际应用价值。     

Enhancement of Na/K pump activity by chronic intermittent hypobaric hypoxia protected against reperfusion injury

Chronic intermittent hypobaric hypoxia (CIHH) has been shown to attenuate intracellular Na(+) accumulation and Ca(2+) overload during ischemia and reperfusion (I/R), both of which are closely related to the outcome of myocardial damage. Na/K pump plays an essential role in maintaining the equilibrium of intracellular Na(+) and Ca(2+) during I/R. It has been shown that enhancement of Na/K pump activity by ischemic preconditioning may be involved in the cardiac protection. Therefore, we tested whether Na/K pump was involved in the cardioprotection by CIHH. We found that Na/K pump current in cardiac myocytes of guinea pigs exposed to CIHH increased 1.45-fold. The K(1) and f(1), which reflect the portion of α(1)-isoform of Na/K pump, dramatically decreased or increased, respectively, in CIHH myocytes. Western blot analysis revealed that CIHH increased the protein expression of the α(1)-isoform by 76%, whereas the protein expression of the α(2)-isoform was not changed significantly. Na/K pump current was significantly suppressed in simulated I/R, and CIHH preserved the Na/K pump current. CIHH significantly improved the recovery of cell length and contraction during reperfusion. Furthermore, inhibition of Na/K pump by ouabain attenuated the protective effect afforded by CIHH. Collectively, these data suggest that the increase of Na/K pump activity following CIHH is due to the upregulating α(1)-isoform of Na/K pump, which may be one of the mechanisms of CIHH against I/R-induced injury.     

Mechanism of salidroside relieving the acute hypoxia-induced myocardial injury through the PI3K/Akt pathway

ObjectiveThe objective was to investigate the anti-inflammatory effects of salidroside through the PI3K/Akt signaling pathway and its protective effects on acute hypoxia-induced myocardial injury in rats.MethodsA total of 24 healthy Sprague-Dawley male rats were selected as the experimental subjects. All rats were divided into 4 groups by using the random number table method, with 6 rats in each group. The groups included the normal control group, the salidroside group, the hypobaric hypoxia group, and the hypobaric hypoxia + salidroside group. Rats in the salidroside group were fed in the original animal laboratory and were intragastrically administered with salidroside every morning at a dosage of 35 mg/kg. Rats in the normal control group were intragastrically administered with an equal dosage of saline. Rats in the hypobaric hypoxia + salidroside group were intragastrically administered with salidroside every morning at a dosage of 35 mg/kg, who were fed in the hypoxic experiment module for animals. The altitude was increased to 4000 m, and the rats were kept in the module for 24 h. Rats in the hypobaric hypoxia group were intragastrically administered with an equal dosage of saline in the same environment, and the altitude was increased to 4000 m after administration. Parameters of blood gas analysis, histopathological changes in cardiac tissues, cardiac indexes, and inflammatory factors IL-6 and TNF-α levels of rats in groups were compared.Results1. The cardiac indexes of rats in groups were compared. The differences between the hypobaric hypoxia group and the hypobaric hypoxia + salidroside group were statistically significant (P < 0.05). 2. The results of blood gas analysis of rats in groups were compared. The differences between the hypobaric hypoxia group and the hypobaric hypoxia + salidroside group were significantly different (P < 0.05). 3. In the hypobaric hypoxia group, the myocardial cells of rats were arranged disorderly and shaped differently, with cases such as edema, degeneration, necrosis, nucleus pyknosis, and massive infiltration of inflammatory cells. In the hypobaric hypoxia + salidroside group, the above-mentioned pathological changes in myocardial cells were relieved. 4. Compared with the hypobaric hypoxia group, in the hypobaric hypoxia + salidroside group, the concentrations of IL-6 and TNF-α in rats decreased apparently, and the differences were statistically significant (P < 0.05).ConclusionSalidroside had the repairing and protective effects on the hypobaric hypoxia-induced myocardial injuries in rats. The application of salidroside could reduce the inflammatory responses of rats with hypobaric hypoxia-induced myocardial injuries through PI3K/Akt signaling pathway, thereby protecting the myocardial cells.     

模拟高原低压低氧环境对大鼠心脏结构和功能影响*

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28 d 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。