间歇缺氧大鼠模型主动脉及心肌结构的改变

目的探讨间歇缺氧对大鼠动脉以及心肌的影响。方法清洁SD大鼠30只,采用成组设计的方法随机分成三组:正常对照组;间歇缺氧组;持续缺氧组。普通饲料饲养,每日缺氧8h,连续35d,然后采用ELISA方法测定血清中NF-kB、MCP-1、VCAM-1的水平;处死大鼠快速分离近心脏的主动脉以及心肌,弹力纤维染色观察结构的改变。结果在持续缺氧组以及间歇缺氧组血清中NF-kB、MCP-1、VCAM-1的水平较正常对照组明显升高,主动脉中膜增厚,弹力纤维中断、排列紊乱,间质胶原纤维增生,心肌细胞肿胀,心肌细胞排列较正常对照组紊乱。结论缺氧可导致主动脉以及心肌细胞增殖、结构紊乱,炎症反应可能为其关键因素。     

缺氧预处理对大鼠钝性心肌挫伤保护作用的研究

目的观察缺氧预处理(HPC)对大鼠钝性心肌挫伤的保护作用,并进一步探讨其机制。方法Wistar大鼠建立钝性心脏挫伤模型,并用常规HE染色、免疫组织化学技术(SP法),结合计算机彩色图像分析技术观察大鼠实验性心脏挫伤及缺氧预处理后Bcl-2、肌钙蛋白T(cTnT)的染色变化。结果免疫组织化学染色①心脏挫伤2h可见大鼠心肌cTnT明显脱失,随着时间延长挫伤组cTnT脱失逐渐加重,与单纯挫伤组相比缺氧预处理组cTnT的脱失显著减轻(P<0.05),对照组心肌未见明显脱失;②对照组有少量Bcl-2表达,单纯挫伤组随时间延长Bcl-2表达逐渐增多,与单纯挫伤组相比缺氧预处理组Bcl-2表达明显增强(P<0.05)。结论Bcl-2的表达说明其参与了心脏挫伤后心肌损伤的形成。缺氧预处理对大鼠钝性心肌挫伤有保护作用,表现为HPC能减轻心肌细胞cTnT的脱失及促进Bcl-2的表达。     

红景天苷对高海拔缺氧条件下大鼠心肌自噬相关通路AMPK的影响

目的 探讨红景天苷保护高海拔缺氧损伤大鼠心脏的可能分子机制。方法 将40只Wistar大鼠随机分为5组：空白对照组（1 500 m）、缺氧生理盐水组（6 500 m+NS）、缺氧Compound C组（6 500 m+comC）、缺氧红景天苷组（6 500 m+Sal）、缺氧红景天苷+Compound C组（6 500 m+comC+Sal）。造模完成后进行血气分析、HE染色、荧光TUNEL检测及Western blot检测。结果 (1)缺氧后大鼠心肌结构发生变化,心肌凋亡加重（P<0.05）,红景天苷治疗可改善心肌细胞病理性损伤,减少心肌细胞凋亡（P<0.05）;(2)缺氧后磷酸化AMPK水平上升,磷酸化mTOR水平降低（P<0.05）。而Compound C组AMPK及mTOR表现呈相反趋势,红景天苷治疗后AMPK及mTOR的表达水平介于Compound C组与红景天苷组之间,但是自噬蛋白Beclin-1的表达较Compound C组增加（P<0.05）。结论 红景天苷可以正向调节AMPK信号通路激活自噬,对缺氧损伤的大鼠心脏起保护作用。     

腺苷酸激活蛋白激酶对缺氧H9c2心肌细胞线粒体自噬及细胞凋亡的影响

目的 探讨腺苷酸激活蛋白激酶[adenosine 5’-monophosphate(AMP)-activated protein kinase,AMPK]对缺氧H9c2心肌细胞线粒体自噬及细胞凋亡的影响及可能机制。方法 实验分为对照组、模型组、AMPK特异性阻断剂（Compound C）组和AMPK激活剂5-氨基咪唑-4-甲酰胺核苷酸转甲酰酶（5-amino-4-imidazolecarboxamide riboside,AICAR）组,采用免疫荧光染色检测线粒体自噬水平;Rhodamine-123和mitotracker双染色及线粒体膜电位检测试剂盒检测线粒体膜电位变化;磷脂结合蛋白V(AnnexinⅤ)-碘化丙啶（propidium iodide,PI）染色检测细胞凋亡率;Western blot检测AMPK、p-AMPK蛋白表达。结果 免疫荧光染色结果显示,与对照组、模型组或Compound C组相比,AICAR组心肌细胞自噬体数增加,差异有统计学意义（P<0.05）。线粒体膜电位变化结果显示,与模型组或Compound C组相比,AICAR组心肌细胞膜电位正常的线粒体比例...     

自噬及凋亡相关蛋白在PC12细胞缺糖缺氧过程中的表达及其意义

目的 探讨自噬及凋亡相关蛋白在PC12细胞缺糖缺氧(OGD)过程中的表达及其意义.方法 将PC12 细胞分为正常对照组、缺糖缺氧1、4和12 h组.MTT法检测细胞存活率,Western印迹法检测各组PC12细胞中BECN1、Bcl-2及Bax蛋白的表达水平.结果 与正常对照组相比,OGD 1及4 h组PC12细胞存活率下降(均P<0.05),BECN1蛋白表达升高,且Bcl-2/Bax比值升高;而与缺糖缺氧1和4 h组相比,OGD 12 h组细胞存活率明显下降(P<0.01),BECN1蛋白表达及Bcl-2/Bax比值亦明显降低.结论 自噬蛋白BECN1及凋亡相关蛋白Bcl-2、Bax参与了PC12细胞OGD损伤过程.在OGD早期,自噬起主要作用,并对OGD PC12细胞起一定的保护作用,随着OGD时间的延长,凋亡在其中占主导地位,促进凋亡蛋白表达,引起PC12细胞的死亡.     

间歇缺氧大鼠海马神经元凋亡及其机制

目的探讨间歇缺氧对大鼠海马组织氧化应激状态及海马神经元凋亡的影响及其可能的机制。方法将36只雄性Wistar大鼠随机分为间歇缺氧组、持续缺氧组和正常对照组，每组12只。采用化学比色法测定海马组织丙二醛和超氧化物歧化酶（SOD）水平，应用Western免疫印迹法检测海马CA1区磷酸化C—JUN氨基末端激酶（p-JNK）、磷酸化c-jun（p-c-jun）的表达水平，应用缺口末端标记（TUNEL）法检测海马CA1区神经元凋亡率。结果间歇缺氧组大鼠海马CAl区丙二醛水平为（1．61±0．39）nmol／mg蛋白，显著高于正常对照组的[（1．25±0．29）nmol／mg蛋白]和持续缺氧组的[（1．34±0．24）nmol／mg蛋白]；间歇缺氧组大鼠海马CAl区SOD水平为（45±13）NU／mg蛋白，显著低于正常对照组[（58±12）NU／mg蛋白]和持续缺氧组[（56±10）NU／mg蛋白]；持续缺氧组与正常对照组的差异均无统计学意义。间歇缺氧组p-JNK、p—c-jun表达显著增高，分别是正常对照组的2．1倍及2．3倍；间歇缺氧组海马CA1区神经元凋亡率为（0．30±0．16）％，显著高于正常对照组[（0．12±0．07）％]和持续缺氧组[（0．17±0．09）]。结论间歇缺氧可导致海马CA1区氧化应激状态，从而激活JNK信号传导通路，介导海马神经元凋亡，这可能是阻塞性睡眠呼吸暂停低通气综合征患者神经功能障碍的病理生理基础之一。【     

自噬参与高糖缺氧诱导的人脐静脉内皮损伤机制的实验研究

目的 观察高糖缺氧状态人脐静脉内皮细胞（HUVECs）自噬水平的变化,探讨自噬在这一过程中所起到的作用。 方法 通过体外细胞培养的方法培养HUVECs并分为6组,即正常对照组、高糖组、正常细胞缺氧组、高糖缺氧组、高糖缺氧+雷帕霉素组、高糖缺氧+3-甲基腺嘌呤（3-MA）组。各组经过相应处理后,通过流式细胞仪、Caspase-3活性试剂盒检测凋亡率、Western blot检测自噬相关蛋白（LC-3、Beclin-1、Atg-5和STSQM1）的表达情况。 结果 与正常缺氧组相比,高糖缺氧组的自噬相关蛋白LC-3B、Beclin-1和Atg-5表达降低,STSQM1表达升高（均P<0.05）,使用雷帕霉素可以上调高糖缺氧组自噬水平并且降低细胞凋亡率,加入自噬抑制剂3-MA使高糖缺氧组自噬下调,细胞凋亡率上升（均P<0.05）。 结论 高糖缺氧状态下HUVECs自噬功能受损,上调自噬可以降低凋亡率,发挥保护细胞的作用。     

在缺氧低压环境下建立高原心脏病大鼠模型及红景天药物干预

目前，国内已建立常压缺氧性大鼠肺动脉高压模型，期待解决慢性支气管炎，肺气肿演变而成的肺源性心脏病。对于肺动脉高压引起慢性高原心脏病的动物模型均在减压缺氧仓内进行，经过模拟高原条件间断缺氧4周后即引起右心室肥厚，实验所设置的条件与实际高海拔地区养殖的大鼠形成肺动脉高压、右心室肥厚所得结果有所不同。我们在海拔3658m和4500m养殖大鼠，观察各组间肺动脉压力及右室变化，采用红景天药物喂大鼠，观察红景天药物在防治高原心脏病大鼠的疗效。     

缺氧及一氧化碳对大鼠血管平滑肌细胞的作用

目的 探讨缺氧及低浓度一氧化碳（ＣＯ）对大鼠血管平滑肌细胞（ＶＳＭＣ）的作用机制。方法 应用改良的Ｌｏｗｒｙ法测ＶＳＭＣ蛋白质含量,Ｆｕｒａ－２荧光指标剂测ＶＳＭＣ内的钙浓度（〔Ｃａ＾２＋〕）,放射免疫环腺苷酸（ｃＡＭＰ）、环一磷酸鸟苷（ｃＧＭＰ）药盒测ｃＡＭＰ、ｃＧＭＰ浓度。结果 （１）缺氧组ＶＳＭＣ内质网扩张,胞浆内出现髓鞘样结构,线粒体肿胀、空泡化。低浓度ＣＯ复合缺氧组ＶＳＭＣ的损害减轻,仅     

大鼠预缺氧模型的制备

目的 制备简单易行的大鼠预缺氧模型,并观察其对脑组织低氧诱导因子-1(HIF-1)α蛋白及mRNA表达的影响.方法 雄性SD大鼠12只,随机分为缺氧组和对照组.缺氧组在固定体积的容器中缓慢输入混合气体,调节氧气和氮气的流入速度,使测氧仪监测到的O2浓度始终保持在12%,然后放入大鼠,每天4 h;对照组大鼠在相同容器中通入空气,每天4 h.7 d后进行免疫组化和RT-PCR测定脑组织HIF-1α蛋白及mRNA表达.结果 缺氧组较对照组脑组织中HIF-1α蛋白和mRNA表达增多(P<0.01).结论 此模型简单易行,达到预缺氧的要求.     

慢性间歇低氧并高血压SD大鼠模型的建立

目的建立慢性间歇低氧并高血压SD大鼠模型,为研究阻塞性睡眠呼吸暂停低通气综合征(OSAHS)并高血压的发病机制提供简单可复制的动物模型。方法氧舱系统分为控制系统、气源系统、暴露舱三个部分。选8~10周龄SD雄性大鼠24只(200~250 g)随机分成间歇低氧干预组和对照组。间歇低氧干预组12只暴露于间歇低氧舱内,白天给予间歇低氧干预(6%~8%的O_2 40 s/21%的O_2 80 s,如此往复循环8 h);对照组12只暴露于常氧舱。在安静状态下检测大鼠尾动脉收缩压,每只连续测量3次,取平均值。结果实验第35天,间歇低氧干预组尾动脉收缩压[(136.21±32.46)mmHg]高于对照组[(121.37±35.37)mmHg](P0.05)。结论控制精确气源通断时间,可有效地模拟间歇低氧过程,重复性佳,是研究间歇低氧所致高血压机制的理想实验模型。     

Affinity of hemoglobin for oxygen and tolerance to hypoxia]

The transfer of O2 in the system between the lung captation and the delivery to tissues is insured by a whole of factors that are components of Fick's equation. The two most important in this O2 transfer are heart output and blood concentration in hemoglobin (transfer capacity of O2). The affinity of blood for O2, evaluated by the determination of P50 (PO2 of half saturation of Hb) interfers also, but we have till presently no precision for what concerns its relative importance. Two demonstrative situations of chronic hypoxia are taken in consideration: adaptation to high altitude hypoxia and the reaction of the system to hypoxia in chronic respiratory deficiency. The influence of displacements of the dissociation curve of HbO2 (Bohr effect, variation in the erythrocytary DPG) is object of discussion. Authors insist particularly on the fact that the fall in the affinity of Hb for O2 (increase in P50) is not always a beneficial mechanism for the delivery of O2 to tissues, particularly in the case of severe hypoxia.     

Chronic-intermittent hypoxia: a model of sympathetic activation in the rat

This review focuses upon the development of a small animal model that incorporates exposure to chronic-intermittent hypoxia to produce systemic hypertension similar to that experienced by humans with the obstructive sleep apnea syndrome. It has been suggested that experimentally-induced hypertension, like human hypertension, is due to activation of the sympathetic nervous system. That hypothesis is supported by physiological studies carried out in humans with obstructive sleep apnea as well as in animals exposed to chronic-intermittent hypoxia. Furthermore, recent anatomical studies of exposed animals strongly suggested that activation was widespread and included cortical and brainstem components of the sympathetic system. Such findings, while illustrating the complexity of modeling human disease in animals, also demonstrate the heuristic value of chronic-intermittent hypoxia as an experimental approach.     

Endocrine changes in a rat model of chronic hypoxia mimicking cyanotic heart disease

OBJECTIVE: The endocrine system plays an important role in the adaptation to hypoxia. The aim of this study is to assess the effect of chronic hypoxia on endocrine changes in a neonatal animal model mimicking cyanotic heart disease. METHODS: Sprague-Dawley rats were placed in a normobaric hypoxic environment at birth and oxygen levels were maintained at 10% in an airtight Plexiglas chamber. Controls remained in room air. Animals were sacrificed at 4 and 8 weeks of life. Hematocrit, Free T4 (FT4), Thyrotropin (TSH), corticosterone, and Growth hormone (GH) were measured. RESULTS: Significant polycythemia developed in the hypoxic rats. Free T4 levels were significantly lower in the hypoxic (H) group compared to the control (C) group at 4 and 8 weeks with FT4 of 2.44 +/- 1.11 ng/dL (H) and 4.35 +/- 1.62 (C) at 4 weeks with a p value < 0.005 and FT4 of 2.01 +/- 0.36 (H) and 3.25 +/- 0.54 (C) ng/dL at 8 weeks with p < 0.01. At 8 weeks TSH levels were significantly lower in the hypoxic group (1.84 +/- 0.9 ng/mL (H) vs. 3.11 +/- 1.1 (C)) with p < 0.05. Corticosterone levels were higher in the hypoxic group with values of 126 +/- 14.8 ng/mL (H) and 114.1 +/- 12.6 (H) at 4 and 8 weeks respectively, when compared to the control group with values of 82.9 +/- 18.1 (C) and 92.7 +/- 10.3 (C) and 4 and 8 weeks with p < 0.0005 and < 0.05 respectively. Growth hormone levels were lower in the hypoxic group at 4 and 8 weeks with p < 0.05 and p < 0.001, respectively. CONCLUSION: Chronic hypoxia in our neonatal rat model was associated with decrease in growth hormone levels and an increase in corticosterone levels. Furthermore, hypoxia resulted in thyroid hormone axis suppression. This effect seems to centrally mediated.     

A mathematical model of tissue-blood carbon dioxide exchange during hypoxia

A two-compartment mass transport model of tissue CO(2) exchange is developed to examine the relative contributions of blood flow and cellular hypoxia (dysoxia) to increases in tissue and venous blood CO(2) concentration. The model assumes perfectly mixed homogeneous conditions, steady-state equilibrium, and CO(2) production occurring exclusively at the tissues. The behavior of the model is compared with published data derived from an isolated dog hindlimb preparation subjected to either reductions in blood flow (ischemic hypoxia) or decreases in arterial PO(2) (hypoxic hypoxia). The results of the model corroborate the experimental finding of greater venous and tissue CO(2) concentrations with ischemic hypoxia than with hypoxic hypoxia. The model also predicts increases in tissue CO(2) concentration under conditions of adequate O(2) supply if CO(2) transfer from tissue to blood becomes impaired. Consequently, from a theoretical perspective, it appears that increases in the tissue or venous blood CO(2) concentration are neither sensitive nor specific markers of tissue dysoxia. The results of the model support the notion that changes in tissue and venous blood CO(2) concentration during dysoxia reflect primarily alterations in vascular perfusion and not scarcity in cellular energy supply.