缺氧性肺动脉高压大鼠肺组织中肾上腺髓质素的合成释放及其意义

目的 探讨缺氧性肺动脉高压（HPH）肺组织中肾上腺髓质素（AM）的合成分泌及其在HPH病理生理过程中的作用。方法 模拟5km高原连接缺氧,复制大鼠HPH动物模型。应用光镜、免疫组化、放射免疫测定等方法,观察测定缺氧后10d、20d、30d和对照组大鼠肺组织中AM蛋白表达及血浆、支气管肺泡灌洗液（BALF）AM含量的动态变化。结果 各组大鼠肺血管内皮细胞（EC）、血管及支气管平滑肌细胞（SMC）、支气管粘膜上皮、肺巨噬细胞（MΦ）、Ⅱ型肺泡上皮及支气管软骨细胞AM均呈阳性表达。缺氧各时相,尤以20d,上述各种细胞表达明显增强;其中EC、SMC、MΦ表达呈强阳性,各时相血浆AM含量显著高于对照组（P＜0.01）。BALF AM含量于缺氧10－20d显著高于对照组（P＜0.01）,且20d明显高于10d;30d含量下降,趋于正常。结论 缺氧可促使肺组织中AM的合成和释放。AM作为一种局部激素及循环激素,对HPH病理过程中肺循环、肺通气、气道免疫及肺血管结构改建等方面发挥重要的调节作用。     

慢性阻塞性肺疾病气道炎症与肺泡巨噬细胞炎症蛋白1α、明胶酶B活性的研究

目的探讨慢性支气管炎(慢支炎)及慢性阻塞性肺疾病(COPD)患者支气管肺泡灌洗液(BALF)及肺泡巨噬细胞(AM)培养上清液中巨噬细胞炎症蛋白1α(MIP-1α)、明胶酶B(MMP-9)的浓度变化.方法用支气管肺泡灌洗技术收集BALF,用ELISA方法测定13例COPD组患者、14例慢支炎组患者和14名正常对照组的BALF和AM培养上清液的MIP-1α、MMP-9浓度.结果慢支炎组及COPD组BALF及AM培养上清液的MIP-1α、MMP-9浓度高于正常对照组(P均<0.05).BALFMIP-1α、MMP-9浓度分别与AM培养上清液MIP-1α、MMP-9浓度呈正相关(r=0.253,P<0.05;r=0.529,P<0.01).BALF中AM数与MIP-1α、MMP-9浓度呈正相关(r=0.558,P<0.01;r=0.405,P<0.01).结论AM是COPD患者肺内MIP-1α、MMP-9的主要细胞来源,MIP-1α及MMP-9通过促进AM等炎症细胞在肺内的聚集而参与了慢支炎及COPD的炎症过程.     

慢性支气管炎气道巨噬细胞计数及淋巴细胞功能相关抗原1的研究

目的探讨慢性支气管炎（慢支炎）气道和粘膜炎症特点及肺泡巨噬细胞（AM）膜上淋巴细胞功能相关抗原1(LFA-1)表达。方法18例吸烟慢支炎临床缓解期患者为研究对象,收集支气管肺泡灌洗液（BALF）及粘膜活检,免疫组织化学方法测灌洗液LFA-1+AM的百分率及绝对数,粘膜内巨噬细胞数目和粘膜厚度。结果(1)慢支炎组中LFA-1+AM数目及其所占百分率明显高于对照组(P均＜0.01);BALF中AM总数与LFA-1+AM数呈正相关（P<0.01)。(2）慢支炎组支气管粘膜厚度［(0.20±0.09)μm］明显高于对照组［（0.08±0.04）μm,P<0.01］;其粘膜内巨噬细胞数［（21.6±4.6)个/高倍镜］明显高于对照组［(10.0±3.4)个/高倍镜,P<0.01］,慢支炎组粘膜厚度、粘膜内巨噬细胞数与一秒钟用力呼气容积(FEV     

转化生长因子β1与一氧化氮合酶及成肌纤维细胞参与大鼠缺氧性肺血管重塑

目的观察转化生长因子β1(TGF-β1)与诱导型一氧化氮合酶(iNOS)基因动态表达变化及成肌纤维细胞形成在大鼠缺氧性肺血管重塑中的作用.方法40只成年雄性Wistar大鼠分成常氧组、缺氧3、7、14 d和21 d组,每组8只,测各组大鼠平均肺动脉压(mPAP)、血管形态学指标、右室肥大指数(RVHI);原位杂交和免疫组化检测TGF-β1、iNOS基因表达,透射电镜观察腺泡内血管壁细胞表型. 结果缺氧7 d后大鼠mPAP升高[(18.41±0.37)mm Hg,P<0.05].缺氧性肺血管重塑、右心室肥大于缺氧14 d后出现.透射电镜证实成肌纤维细胞含有特异性的微丝和丰富的粗面内质网.TGF-β1mRNA于缺氧3 d、7 d表达增高不明显,缺氧14d增高(0.385±0.028,P<0.01);TGF-β1蛋白在常氧组呈弱阳性,缺氧3 d表达增强(0.198±0.031,P<0.01),缺氧7 d组达高峰(0.267±0.035,P<0.01).对照组大鼠肺动脉壁iNOS mRNA弱阳性,缺氧3 d后表达增强(0.245±0.036,P<0.01),缺氧7 d达高峰水平(0.318±0.034,P<0.01),以后维持于高峰水平;iNOS蛋白在常氧组大鼠肺动脉中膜iNOS弱阳性,缺氧3 d始增高(0.225±0.030,P<0.01),缺氧7 d起稳定于高水平.结论缺氧诱导TGF-β1和iNOS动态表达变化及肺血管成肌纤维细胞的形成参与大鼠缺氧性肺血管重塑.     

慢性支气管炎患者肺泡巨噬细胞及诱导痰中内皮素的研究

目的研究慢性支气管炎(慢支炎)患者诱导痰中、肺泡巨噬细胞(AM)培养上清液中及在氨茶碱和脂多糖(LPS)干预下培养上清液中内皮素(ET)的浓度变化,探讨AM源性ET在慢支炎及慢性阻塞性肺疾病(COPD)病理进展过程中的作用.方法选择慢支炎患者14例,COPD患者13例,同时选择14名健康人作为正常对照.支气管肺泡灌洗技术收集支气管肺泡灌洗液(BALF),对其细胞成分进行计数和分类;对其中26例用高渗盐水诱痰法取痰标本,放射免疫法测定诱导痰中和AM培养上清液中的ET浓度.结果(1)慢支炎组、COPD组BALF中细胞总数、中性粒细胞数、肺泡巨噬细胞数均明显高于正常对照组(P均<0.01);(2)慢支炎组和COPD组AM培养上清液中ET浓度和诱导痰中ET浓度明显高于正常对照组(P均<0.01),但慢支炎组与COPD组之间差异无显著性(P均>0.05);(3)三组的诱导痰ET浓度与AM培养上清液ET浓度呈正相关(r=0.741,P<0.01),与AM数呈正相关(r=0.597,P<0.01);(4)COPD组AM培养上清液ET浓度、诱导痰ET浓度均与一秒钟用力呼气容积占预计值%(FEV1占预计值%)呈负相关(r=-0.828,P<0.01;r=-0.748,P<0.05);(5)氨茶碱对AM培养上清液中ET浓度无影响(P>0.05),而LPS使其浓度明显升高(P<0.01).结论(1)慢支炎、COPD患者气道腔内存在非特异性气道炎症,其特点表现为中性粒细胞和巨噬细胞数目增多;(2)AM为肺内ET的重要来源之一,LPS可刺激AM分泌ET,AM源性ET可能参与了COPD阻塞性通气功能障碍的病理进展过程.     

肺心病患者血浆肾上腺髓质素、神经肽Y与缺氧性肺动脉高压的关系

目的 观察缺氧性肺动脉高压患者血浆肾上腺髓质素（ADM）和神经肽Y（NPY）的水平变化,探讨ADM、NPY与缺氧性肺动脉高压的关系和缺氧性肺动脉高压的发病机制.方法 选择慢性阻塞性肺病（COPD）并肺动脉高压、肺心病患者（HPH组,30例）和健康体检者（对照组,20例）,用放免法测定血浆ADM、NPY的含量,并同时测定其血氧分压和肺动脉压力.结果 （1）HPH组血浆ADM、NPY含量高于对照组（HPH组为65.79±25.72、209.01±42.25,对照组为15.26±3.57、135.52±20.12;t=10.15,7.29;P＜0.01）;（2）血浆ADM、NPY与氧分压呈负相关（r=-0.79,-0.67;P＜0.01）;（3）血浆ADM与NPY呈正相关关系（r=0.48;P＜0.01）.结论 ADM、NPY参与了缺氧性肺动脉高压发生、发展的病理生理过程.     

缺氧性肺动脉高压大鼠血浆降钙素基因相关肽和内皮素-1的测定及其相互关系

为了探讨血浆降钙素基因相关肽和内皮素—1含量及其相互关系在缺氧性肺动脉高压调节机制中的作用,将Wistar大鼠20只分为:一周缺氧组(5只,一周对照组(5只),二周缺氧组(5只)及二周对照组(5只),低氧处理采用常压低氧舱,舱内氧浓度10±0.5%,用放射免疫方法测定对照组和不同缺氧时间组大鼠血浆降钙素基因相关肽和内皮素—1含量.并通过P_(50)压力传感器法测定其肺动脉平均压。结果表明在缺氧性肺动脉高压大鼠中,一周缺氧组血浆降钙素基因相关肽含量与一周对照组比降低,血浆内支素—1含量与一周对照组比增高,但均无显著差异(t=1.58,2.24,P>0.05)。二周缺氧组血奖降钙素基因相关肽含量与二周对照组比明显降低,血浆内皮素含量与对照组比明显增高(t=2.61,2.31。P<0.05),肺动脉压力与血浆降钙素基因相关肽水平呈明显负相关,与内皮素—1水平呈明显正相关(负相关系数R=0.910,P<0.01)。这一研究结果说明血浆降钙素基因相关肽和内皮素—1共同参与缺氧性肺动脉高压调节。     

慢性阻塞性肺疾病患者肺泡巨噬细胞合成肾上腺髓质素的研究

目的探讨肺泡巨噬细胞合成肾上腺髓质素(ADM)在慢性阻塞性肺疾病(COPD)中的作用与机制。方法选择2003年10月至2004年3月,北京大学深圳医院呼吸科15例COPD住院患者(COPD组)和同期14名健康体检者(对照组),收集其肺泡灌洗液,用放免法测定血浆、支气管肺泡灌洗液(BALF)和肺泡巨噬细胞(AM)培养上清液ADM的浓度。结果(1)COPD组BALF的细胞总数、中性粒细胞(PMN)及AM较对照组显著增高(P<0.01)。(2)COPD组血浆、BALF和AM培养上清液ADM浓度均较对照组增高(P<0.01)。(3)COPD组血浆及BALF的ADM浓度分别与BALF中AM数呈正相关(r分别为0.467和0.448,P均<0.05),血浆与BALFADM浓度亦分别与AM培养液中ADM浓度呈正相关(r分别为0.791和0.874,P均<0.01)。结论COPD患者气道内AM增加,合成ADM增多,是BALF中ADM的重要来源,从而在COPD气道炎症、肺通气及肺动脉高压中发挥广泛调节作用。     

慢性肺原性心脏病病理生理过程中肾上腺髓质素的变化

目的　探讨肾上腺髓质素(ADM)在慢性肺原性心脏病(肺心病)的病理生理过程中 的作用。方法　选肺心病患者30例分别于急性加重期和缓解期采用放免法测定血浆ADM、内皮 素 1(ET)含量,同时检测动脉血气指标(PaO2、PaCO2、pH)和肺动脉收缩压(PASP),使用彩色多普 勒超声诊断仪测定,另取20名健康人同时测定ADM、ET含量,作为对照组。结果　肺心病患者发 作期和缓解期的ADM、ET含量均明显高于对照组(P<0.01),发作期明显高于缓解期(P<0.01); 肺心病患者血ADM含量与PASP呈显著正相关(OR=0.917,P<0.01),与PaO2呈负相关(OR= 0.642,P<0.05),发作期Ⅰ型呼吸衰竭与Ⅱ型呼吸衰竭患者血中ADM含量比较差异无显著性(P >0.05)。结论　ADM参与了肺心病的病理生理过程,缺氧可刺激ADM的合成和分泌,PaO2、ADM 对肺动脉压的调节有直接影响,并且在缺氧性肺动脉高压中对肺血管张力的调节具有一定的作用。     

一氧化氮对缺氧性肺动脉高压大鼠血浆降钙素基因相关肽含量的影响

目的 探讨一氧化氮(NO)对缺氧性肺动脉高压(HPH)大鼠血浆降钙素基因相关肽(CGRP)含量的影响。方法 将Wistar大鼠40只分为四组:对照组(n=10),缺氧组(n=10),缺氧 L-NAME组(n=10),缺氧 L-Arg组(n=10)。通过P50压力传感器法测量定四组大鼠肺动脉平均压(PAMP),用放射免疫方法测定各组大鼠血浆CGRP的含量。结果 缺氧组的PAMP显著高于对照组(P<0.05),缺氧 L-Arg组的PAMP显著低于缺氧组(P<0.05);缺氧组的有室(RV)千重/左室 室间隔(LV S)干重比值显著高于对照组(P<0.01),缺氧 L-NAME组的RV/LV S比值显著高于缺氧组(P<0.05)及缺氧 L-Arg组(P<0.01),缺氧 L-Arg组的CGRP含量最高,与缺氧 L-NAME组和缺氧组有高度显著性差异(P<0.01,P<0.05),PAMP与血浆CGRP含量呈明显负相关(r=-0.426,P<0.05)。结论 通过上述试验推测NO可能通过影响CGRP的释放调节HPH。     

丹参对慢性低氧大鼠肺动脉压力等的影响

目的：探讨丹参(salvia miltiorrhiza bunge,SMB)对慢性低氧大鼠肺动脉压的急性治疗作用和血中羟脯氨酸（hydrox yproline ,Hyp）含量的影响。方法：用右心导管法和氯胺T氧化比色法检测正常和低氧3周大鼠的血流动力学指标及血中羟脯氨酸含量，并观察从肺动脉注射不同剂量的丹参后上述 各项指标的改变。结果：低氧3周可引起大鼠肺动脉高压和血中 羟脯氨酸含量增高，经肺动脉注射丹参后可明显降低已增高的肺动脉压力和增加心输出量及降低体动脉压（P＜0．05），但对血中羟脯氨酸含量影响无统计学意义（P＞0．05）。结论：丹参对慢性低氧大鼠的急性疗效可能与扩张肺血管和改善微循环有关。     

CGRP在慢性低氧性肺动脉高压大鼠肺中的表达

:本研究观察慢性低氧性肺动脉高压大鼠肺中 CGRP表达的相对含量及其动态变化。应用免疫组织化学 ABC染色法观察大鼠在减压低氧条件下 1周 ,2周 ,4周及正常大鼠肺组织 CGRP的相对含量。结果显示 :低氧使大鼠肺动脉压显著增加 ,且随低氧时间的延长而进一步增高 ,第 1周增加的速率明显加快 ;低氧大鼠肺中 CGRP的表达量明显高于正常对照大鼠 （P<0 .0 1） ,CGRP的表达量依次为低氧 4周 >低氧 1周 >低氧 2周 >正常对照。提示 :CGRP参与慢性低氧性肺动脉高压形成过程中的调节 ;CGRP在慢性低氧中的表达呈阶段性增加 ,可能与低氧早期 CGRP大量释放后造成暂时性耗竭有关。     

碱性成纤维细胞生长因子在低氧性肺动脉高压大鼠肺内表达…

OBJECTIVE: To evaluate the role of bFGF in the development of hypoxic pulmonary hypertension. METHOD: Rat models with chronic hypoxia induced pulmonary hypertension were established, the pulmonary hemodynamics were measured and the pulmonary arterioles change were studied with morphometric analysis under light microscopes, immunohistochemical staining with monoclonal antibody against human recombinant bFGF was performed in the paraffin section of rat lung. RESULT: (1) The mean pulmonary artery pressure (mPAP), and the ratio of the thickness of pulmonary arteriolar wall to external diameter of pulmonary arterioles (MT%) were 3.96 +/- 0.47 kPa and 33.8% +/- 3.5% in rats exposed to hypoxia for 3 weeks respectively, both were significant higher than those in normal control group, P < 0.01. (2) The positive staining for bFGF in the wall of pulmonary arterioles in hypoxic rats was stronger than that of control group (P < 0.01), there was a statistical relationship between increase of staining for bFGF and MT% in rats exposed to hypoxia. CONCLUSION: (1) Hypoxia can induce formation of pulmonary hypertension and structual remodeling of pulmonary arterioles. (2) bFGF may modulate the structure remodeling of pulmonary arterioles in chronic hypoxic pulmonary hypertension.     

等容稀释对缺氧大鼠肺血液动力学的影响

本文探讨等容稀释对常压缺氧大鼠肺血液动力学的影响。等容稀释明显降低缺氧大鼠的肺动脉高压,同时不影响其肺气体交换及颈动脉压力。这表明血红细胞增多导致的高血液粘滞度更大地影响肺循环。我们还发现,缺氧大鼠血浆中丙二醛及全血超氧化物歧化酶明显低于正常,而血浆中环磷酸鸟苷却明显高于正常组。这些改变可能参与缺氧性肺动脉高压的调节。     

Effect of alveolar pressure on pulmonary artery pressure in chronically hypoxic rats

The effect on pulmonary artery pressure of a rise in alveolar pressure differed in chronically hypoxic rats (10% O2 for 3-5 weeks) compared with control rats. Chronically hypoxic rats have newly muscularised walls in arterioles in the alveolar region. Isolated lungs of chronically hypoxic and control rats were perfused with blood under conditions in which alveolar pressure was greater than left atrial pressure during both normoxia and hypoxia. Alveolar pressure was the effective downstream pressure. Pressure-flow lines were measured at low and high alveolar pressure (5 and 15 mmHg). During normoxia pressure-flow lines of chronically hypoxic rats had a steeper slope (higher resistance) and greater extrapolated intercept on the pressure axis (effective downstream pressure) than control rats. In both groups of rats the change from low to high alveolar pressure during normoxia caused an approximately parallel shift in the pressure-flow line similar to the change in alveolar pressure. During hypoxia, which led to an increase in slope and intercept in both groups of rats, the effect of a rise in alveolar pressure differed in chronically hypoxic from control rats. In control rats there was a small parallel shift in the pressure-flow line that was much less than the increase in alveolar pressure; in chronically hypoxic rats there was a large parallel shift in the pressure-flow line that was greater than the increase in alveolar pressure. Thus in chronically hypoxic rats hypoxic vasoconstriction probably occurred mainly in muscular alveolar vessels, whereas in control rats it probably occurred upstream in extra-alveolar vessels. At constant blood flow the relation between pulmonary artery pressure and alveolar pressure was measured while alveolar pressure was reduced from approximately 15 mmHg to zero during both normoxia and hypoxia. In control and chronically hypoxic rats the slope of this line was less than 1. At an alveolar pressure of 2-3 mmHg there was an inflection point below which the line was nearly horizontal in control but negative in chronically hypoxic rats. During hypoxia the inflection point increased in control but not in chronically hypoxic rats, whereas the preinflection slope became negative. Apart from a rise in pulmonary artery pressure at all values of alveolar pressure, which occurred in both groups of rats, there was no change in the form of the curve in chronically hypoxic rats during hypoxia. These results also suggest constriction of extra-alveolar vessels in control rats and alveolar vessels in chronically hypoxic rats during hypoxia.     

肺动脉高压患者血浆肾上腺髓质素水平与肺动脉压力的关系

目的：探讨肺动脉高压（pulmonary hypertension,PH)患者血浆肾上腺髓质素（a-drenomedullin,AM)的浓度与肺动脉压力的关系。方法：选择正常肺动脉压力患者和轻度、中度、重度肺动脉高压患者各10例，在术中分别从肺动脉和肺静脉中抽血用放射免疫法测定AM含量。结果：肺动脉血浆AM浓度与肺动脉压力呈显著正相关；肺静脉血浆AM浓度低于肺动脉AM浓度，且其浓度差值与肺动脉压力呈显著正相关。结论：AM参与了肺动脉高压的病理生理过程，并在肺内部分代谢，对肺血管张力的调节起重要作用。     

Autologous macrophages in combined therapy of patients with tuberculosis complicated by nonspecific bronchitis

The function of the lung macrophagal system was estimated in patients with pulmonary tuberculosis complicated by nonspecific inflammatory processes. A decrease in the absolute and relative contents of alveolar macrophages (AM) in bronchoalveolar lavage fluid (BALF) and their lower absorbing activity were revealed. Autologic macrophages from blood monocytes had higher functional activity than AM. Introduction of autologic macrophages into the bronchial tree in the patients with tuberculosis associated with catarrhal and purulent endobronchitis promoted normalization of the BALF cytograms, increasing AM activity and involution of the specific and nonspecific processes.     

P130cas在低压低氧肺动脉高压大鼠中的表达

目的探究P130cas(Crk associated substrate)在低压低氧肺动脉高压大鼠血清及组织中的表达。方法将20只大鼠随机分为正常对照组和低压低氧组。正常对照组在正常环境下饲养28天,低压低氧组在低压低氧舱(低压低氧舱模拟海拔5000米高度)饲养28天。右心导管方法测定各组大鼠肺动脉压力,ELISA方法测定每组大鼠血清中P130cas表达,免疫组化检测肺动脉中P130cas的表达,应用Western blot测定大鼠肺组织中P130cas蛋白表达量。结果低压低氧组大鼠平均肺动脉压力较正常对照组明显升高,且达到肺动脉高压诊断标准;低压低氧组P130cas在大鼠血清及肺组织中的表达较对照组明显升高。结论P130cas可能参与了低压低氧肺动脉高压的形成。