缺氧对幼猪肺组织和肺小动脉壁钙调蛋白活性量的影响

作者观察了慢性缺氧对幼猪肺组织和肺小动脉壁钙调蛋白活性量的影响。缺氧动物的上述组织均在缺氧条件下取出。结果表明,①慢性间断性低压缺氧的幼猪在4000m模拟高原肺动脉增压反应明显。②缺氧动物肺组织钙调蛋白活性量较平原组显著增高。③在肺小动脉持续收缩时,取材测得肺小动脉壁钙调蛋白活性量与平原组相比无显著改变。说明缺氧性肺小动脉收缩不是通过影响平滑肌细胞内钙调蛋白活性量而实现的。     

兔网织红细胞钙调蛋白含量及阿片肽对兔网织红细胞膜钙调蛋白活性的影响

用以激活环核苷酸磷酸二酯酶活性为基础的钙调蛋白(Calmodulin CaM)活性测定法,测定正常兔红细胞及兔网织红细胞CaM含量及阿片肽类对兔网织红细胞膜CaM活性的影响。发现无论在网织细胞或其细胞膜CaM含量均明显高于正常红细胞;β-内啡肽和强啡肽对兔网织细胞膜CaM活性有显著的抑制作用,这种作用并不为纳洛酮或其化合物Mr2266所拮抗,也不受钙离子浓度增加的影响,但可被外源性CaM所翻转。推论兔网织细胞膜CaM是β-内啡肽和强啡肽作用环节之一.     

钙调蛋白的分子生物学

钙是机体重要的调节因子之一,它同CAMP一样可作为第二信使广泛参与生命活动的调控。现已证实,钙几乎都是与钙调蛋白(Calmodulin,CaM)结合成活性复合物而完成其调控功能。CaM的分布无所不在,且与钙平行,标志着它具有普遍的生物     

磷酸肌酸钠对缺氧幼鼠脑组织中钙调蛋白、一氧化氮水平的影响

目的:研究磷酸肌酸钠(PCr)对缺氧幼鼠脑组织中钙调蛋白(CaM)及一氧化氮(NO)水平的影响.方法:将75只SD幼鼠随机分为磷酸肌酸钠治疗组(PCr组)、模型组和正常对照组3组,PCr组和模型组制成缺氧模型,并于缺氧前0.5 h、缺氧后即刻、24 h和48 h分别腹腔注射PCr和等量生理盐水,正常对照组不作缺氧处理.各组大鼠于缺氧后6 h观察脑组织的病理改变,于48 h检测脑组织中CaM及NO含量的变化.结果:缺氧后6 h,PCr组较模型组神经细胞破坏减少,水肿、坏死明显减轻.3组幼鼠脑组织中CaM和NO含量差异均有统计学意义(F分别为27.425和22.137,P<0.001).PCr组的CaM含量[(41.19±1.13) ng/L]较正常对照组[(39.56±0.86) ng/L]稍高(P<0.05),但较模型组[(42.04±0.76) ng/L]降低(P<0.05);PCr组的NO含量[(0.73±0.13) μmol/g]较正常对照组[(0.55±0.07) μmol/g]稍高(P<0.05),但较模型组[(0.86±0.17) μmol/g]降低(P<0.05).结论:PCr可以通过降低脑组织中CaM、NO的含量而发挥对缺氧所致的脑损伤的神经保护作用.     

大鼠全脑缺血及灌注时不同脑区钙调蛋白含量的变化

本研究采用阻断大鼠四条血管的全脑缺血模型,用酶联免疫吸附测定法观察下丘脑、海马、额叶大脑皮层和小脑中钙调蛋白(CaM)含量的变化。结果发现缺血30min后,除额叶大脑皮层外,上述脑区的CaM含量都明显下降;缺血30min再灌注6h后,CaM含量又进一步下降。提示在急性全脑缺血所致脑细胞损伤的发生发展过程中,脑组织中CaM含量的降低可能起着重要作用。     

复方丹参注射液对家兔低氧性血管收缩反应的影响

本实验观察了复方丹参注射液对低氧性肺动脉高压家兔肺循环、体循环、心电图ST段及动脉气含量的影响。结果表明，复方丹参注 可对抗低氧所致肺动脉压升高，降低肺血管阻力；心输出和每搏输出量明显高于对照组，同时可改善缺氧动物动脉血氧分压和降低严重缺氧所致心电图ST段下移程度。     

压宁定与前列腺素E1对肺动脉高压血流动力学的对比研究

目的　对比研究压宁定与前列腺素E1(PGE1)对治疗肺微血管栓塞肺动脉高压犬的血流动力学效果。方法　采用S G漂浮导管及 96 0循环电脑监测仪等方法 ,观察用药前后各组肺动脉高压模型犬的血流动力学指标及肺循环指标。结果　对照组无明显变化。与PGE1组比较压宁定组降低肺动脉压和肺循环阻力的时效更长。 3组均对心率无明显影响 ,压宁定及PGE1均影响体循环 ,但PGE1影响体循环时间更长。结论　压宁定具有较好肺血管扩张选择性 ,而对全身血流动力学影响较小 ,治疗肺动脉高压优于PGE1。     

miR-335在急性缺血性脑卒中表达下调及对钙调蛋白的调控作用

目的 检测微小RNA-335在急性缺血性脑卒中（AIS）患者血清中的表达,并探讨其对钙调蛋白（CaM）调控的作用机制。 方法 采用实时荧光定量聚合酶链反应（qRT-PCR）法测定106例AIS患者及98例健康对照组血清中miR-335表达情况;用生物信息学数据库查询分析miR-335对钙调蛋白编码基因CALM1的靶向结合关系;脂质体转染法将miR-335模拟物、抑制物以及相应阴性对照物分别转染至人脐静脉内皮细胞（HUVECs）中并进行细胞培养,采用逆转录PCR（RT-PCR）和Western blot分别检测干预后HUVECs中钙调蛋白mRNA和蛋白的表达水平。 结果 与健康对照组相比较,AIS组患者血清miR-335表达明显下调（P<0.01）;生物信息学软件的查询分析显示CALM1存在miR-335潜在靶向结合位点;RT-PCR和Western blot检测结果显示miR-335模拟物组CaM mRNA和蛋白的表达水平较对照组显著下降（P<0.01）,而miR-335抑制物组CaM mRNA和蛋白的表达水平较对照组显著增高（均P<0.05）。 结论 急性缺血性脑卒中患者血清miR-335表达明显下降,表达下调的miR-335可能通过上调钙调蛋白的表达从而发挥重要作用。     

乌拉地尔对风心病肺动脉高压及血气的影响

目的：观察乌拉地尔对合并有肺动脉高压的风心病病人右心血流动力学及动脉血气的影响。方法：以风心病继发肺动脉高压的34例病人为研究对象，观察静脉注射0.4mg/kg乌拉地尔前、后10min、40min、60min右心血流动力学参数、体循环血压及动脉血气的变化。结果：乌拉地尔能显著降低风心病病人的肺动脉压、肺循环阻力、肺毛细血管楔嵌压及体循环血压，但对肺循环的影响要明显强于体循环，并几乎不引起心率，心输出量及动脉血气的改变。无严重副反应性。结论：乌拉地尔治疗术前风心病肺动脉高压可能有很好的临床效果。     

鼻咽癌细胞培养上清对正常人淋巴细胞钙调蛋白、白细胞介素-2、白细胞介素-2受体活性及T淋巴细胞增殖的影响

观察鼻咽癌低分化细胞株(CNE-2)培养上清(CNE-2S)对正常人外周血淋巴细胞(PBL)的作用,结果表明:CNE-2S可明显抑制正常人T淋巴细胞的增殖,白细胞介素-2(IL-2)的产生及钙调蛋白(CaM)的活性。但对IL-2受体活性无明显影响。提示CNE-2S有可能是通过抑制淋巴细胞内CaM的活性,使细胞代谢改变,而阻碍T淋巴细胞增殖。     

慢性缺氧大鼠肺组织钙调素活性研究

为探讨钙调素（ＣａＭ）在慢性缺氧性肺动脉高压发病中的作用，将４０只Ｗｉｓｔａｒ大鼠随机分为四组，Ⅰ组为正常对照组，不接受任何处理。Ⅱ、Ⅲ、Ⅳ组为实验组，分别间断缺氧１、２、３周，而后采用火焰原子吸收分光光度法及磷酸二酯酶法测定四组大鼠肺组织Ｃａ２＋含量及ＣａＭ活性。结果显示：缺氧１、２、３周均能引起大鼠平均肺动脉压（ｍＰＡＰ）及肺血管阻力（ＰＶＲ）增高，心输出量（ＣＯ）降低；缺氧大鼠肺组织Ｃａ２＋含量及ＣａＭ活性较正常对照组增高，其中缺氧２周及３周组大鼠肺组织ＣａＭ活性与正常对照组比较有显著性差异（Ｐ＜０．０５），但缺氧１周组大鼠ＣａＭ活性与正常对照组比较差异无统计学意义；肺组织Ｃａ２＋含量与ＣａＭ活性呈明显正相关（Ｐ＜０．０５），提示Ｃａ２＋－ＣａＭ系统在大鼠缺氧性肺动脉高压的发生中起一定作用。细胞内Ｃａ２＋浓度增高，可促使ＣａＭ由细胞骨架移行到细胞浆内，可能是慢性缺氧大鼠肺组织ＣａＭ活性增高的原因之一。     

一氧化氮对急、慢性缺氧大鼠血流动力学及缺氧性肺血管收缩反应的影响

观察了吸入０．００４％的一氧化氮（ＮＯ）对急、慢性缺氧大鼠血流动力学、缺氧性肺血管收缩反应（ＨＰＶ）、血气及高铁血红蛋白（ＭｅｔＨｂ）的影响。结果表明：（１）常氧吸入ＮＯ时能明显降低慢性缺氧大鼠肺动脉平均压（Ｐｐａ）和肺血管阻力（ＰＶＲ），但对正常大鼠的Ｐｐａ和ＰＶＲ无明显影响；（２）慢性缺氧大鼠急性缺氧时ＨＰＶ较正常大鼠弱，吸入ＮＯ不但降低两者的急性缺氧肺动脉高压，且完全逆转两者的ＨＰＶ；（３）吸入ＮＯ对急、慢性缺氧大鼠体循环血流动力学、血气及ＭｅｔＨｂ含量无明显影响。提示吸入ＮＯ能选择性降低，急、慢性缺氧性肺动脉高血压，且逆转ＨＰＶ。     

Effects of Hypoxia on Calmodulin Levels of Lung Tissues and Small Pulmonary Arterial Walls in Young Pigs

The effects of chronic hypoxia on calmodulin levels of lung tissues and small pulmonary ar-terial walls were studied in young pigs, The tissue specimens of hypoxic animals were obtained underhypoxic conditions. The following results were collected:(1) The swine exposed to chronic intermittent hypoxia showed a significant pulmonary pressor re-sponse at a simulated high altitude of 4000 m.(2) A higher level of calmodulin was found in the lung tissues of chronic hypoxic animals. It maybe related to the increased release of some vaosactive substances from pulmonary non-muscularcalls.(3) No significant difference of calmodulin level of small arterial walls was demonstrated between theexperimental animals and the control.The findings suggest that pulmonary vasoconstriction due to hypoxia is not likely to be associatedwith obvious change in calmodulin level in the smooth muscle of blood vessels.     

Effects of captopril in patients with chronic obstructive pulmonary disease and secondary pulmonary hypertension

Ten patients with chronic obstructive pulmonary disease (COPD) with normal left ventricular function were given a single dose of captopril (0.25 mg/kg). Mean systemic arterial pressure, heart rate and coronary flow to the right ventricle were reduced significantly after captopril. In contrast captopril did not cause a significant fall in pulmonary arterial pressure or pulmonary vascular resistance. We conclude that captopril fails to produce haemodynamic benefits in such hypoxic patients and that angiotensin II is not playing a significant role in maintaining pulmonary vasoconstriction.     

Effects of acute ingestion of ethanol on hemodynamics and hypoxic pulmonary vasoconstriction in dogs—Role of leukotrienes

Summary The effects of acute intragastric administration of ethanol on hemodynamics and hypoxic pulmonary vasoconstriction were studied in spontaneously breathing dogs. The dogs were given 0.5 g/kg of 10 % ethanol (v/v) in 5 min. Hemodynamic measurements were obtained before and 30 min after ingestion of ethanol. Mean pulmonary arterial pressure and pulmonary vascular resistance increased markedly after ingestion of ethanol, and hypoxic pulmonary vasoconstriction was augmented significantly by ethanol as well. Diethylcarbamazine citrate (DEC), a lipooxygenase inhibitor, inhibited these effects of ethanol in a dosage of 200 mg/kg. The above findings suggest that ethanol can induce pulmonary vasoconstriction, which may be predominantly mediated by leukotrienes (LTs).     

扩血管药对大鼠急性缺氧性肺动脉高压的影响——川芎嗪、汉防己甲素、酚苄明及酚妥拉明的作用

川芎嗪(80mg/kg体重)及酚苄明(0.25mg/kg体重)扩张肺血管,增加心输出量,抑制缺氧性肺血管收缩,而且对体循环的影响较小;汉防已甲素(1.85mg/kg体重)减慢心率,降低体肺循环压力及阻力,也能减弱缺氧性肺血管收缩;酚妥拉明虽然迅速降低体肺循环的压力和阻力,但不能减弱缺氧性肺血管收缩。这提示川芎嗪及酚苄明对缓解肺动脉高压,改善心功能可能疗效较好。     

Effects of Salvia miltiorrhizae composite injection on hypoxic pulmonary vasoconstriction in rabbits]

In the present experiment, the hemodynamic effect of Salvia miltiorrhizae composite injection (SMCI) on pulmonary and systemic circulation during hypoxic pulmonary arterial hypertension was observed. The results showed that the pulmonary arterial pressure increased at first in both group, then decreased gradually, but in SMCI group decreased much more than in the control group. The pulmonary vascular resistance increased very significantly in the control group, but in SMCI group considerably decreased after administration, then keeping at a level little more than the normal. Difference between groups was very significant. The stroke volume increased slightly at first and then decreased persistently in the control group, but increased significantly and kept at a higher level in SMCI group. The protective effects of SMCI on hypoxic myocardium was studied by observing ST-segment on ECG. It was found that the ST-segment fell in both groups, but the degree of fall in SMCI was much less than in the control group. It was found that the PaO2 was 35.1 +/- 2.6 in the control group, 38.1 +/- 2.4 in SMCI group. Difference between groups was significant (P less than 0.05.) The above results suggest that SMCI can diminish hypoxic pulmonary vasoconstriction, improve PaO2 in hypoxic animal and protect hypoxic myocardium. Hence, SMCI can be used to prevent and treat hypoxic pulmonary arterial hypertension.     

补钙可减弱犬缺氧性肺血管收缩反应

研究补充钙对缺氧性肺血管收缩反应及脑血管舒张反应的影响。在全麻狗,静脉滴注ＣａＣｌ２生理盐水（１ｍｇ·ｋｇ－１·ｍｉｎ－１）。用原子吸收光谱法测定血清钙,输钙前后分别测常氧与缺氧时血流动力学指标,并测右颈总动脉血流量反映相对脑血流量（ＣＢＦ）。以缺氧时肺血管阻力（ＰＶＲ）和ＣＢＦ变化率（ｄＰＶＲ％,ｄＣＢＦ％）反映血管反应强度。结果：常氧下血清钙从１．６５～１．８５ｍｍｏｌ／Ｌ增加至３．１０～３．２０ｍｍｏｌ／Ｌ时可降低平均肺动脉压（ｍＰＡＰ）（Ｐ＜０．０１）,此时平均体动脉压、体血管阻力、心输出量（ＣＯ）和ＣＢＦ均无明显变化。补钙前吸１０％氧５ｍｉｎ时ｍＰＡＰ、ＰＶＲ、ＣＢＦ、ＣＯ都增加（均为Ｐ＜０．０１）。补钙后缺氧５ｍｉｎ,ｍＰＡＰ、ＰＶＲ增高程度和ｄＰＶＲ％均较未用钙时小（Ｐ分别为＜０．０５、＜０．０１、＜０．０１）,ＣＢＦ的变化无显著性意义。提示补一定浓度钙可减轻缺氧性肺动脉高压而无增强缺氧性脑血管舒张反应的副作用。     

慢性缺氧大鼠肺组织钙调素活性研究

为探讨钙调素在慢性缺氧性肺动脉高压发病中的作用，将４０只Ｗｉｓｔａｒ大鼠随机分为四组，Ｉ组为正常对照组，不接受任何处理。Ⅱ、Ⅲ、Ⅳ组为实验组，分别间断缺氧１、２、３周，而后采用火焰原子吸收分光光度法及磷酸二酯酶法测定四组大鼠肺组织Ｃａ＾２＋含量及ＣａＭ活性。