慢性低氧性肺动脉高压大鼠肺内血管内皮生长因子表达的变化

为了解低氧对肺内血管内皮生长因子（ＶＥＧＦ）基因表达的影响及ＶＥＧＦ在肺动脉高压发生中的作用，以常压低氧建立大鼠肺动脉高压模型，采用Ｅｌｉｓａ法检测大鼠肺动脉血血清ＶＥＧＦ的含量改变，以体外转录并用ＤＩＧ－ＵＴＰ标记的ＶＥＧＦｃＲＮＡ探针进行肺组织原位杂交，检测大鼠肺内ＶＥＧＦｍＲＮＡ表达的变化。结果发现：低氧３周后，大鼠形成明显的肺动脉高压；大鼠肺动脉血血清中ＶＥＧＦ含量在低氧３周组为４２０．３±７３．１ｐｇ／ｍｌ，明显高于对照组的３２２．２±５８．１ｐｇ／ｍｌ（Ｐ＜０．０１）；原位杂交显示，低氧大鼠肺小动脉管壁出现明显的ＶＥＧＦｍＲＮＡ表达，说明低氧在引起肺动脉高压的同时可刺激肺小动脉管壁，使ＶＥＧＦｍＲＮＡ表达增强，导致ＶＥＧＦ的合成和分泌增加，后者可能在低氧性肺动脉高压发生过程中起一定的作用。     

血管内皮生长因子在低氧性肺动脉高压大鼠肺内的分布和水平变化

为了解低氧性肺动脉高压时肺内血管内皮生长因子（ＶＥＧＦ）的改变及其意义，以常压低氧建立大鼠肺动脉高压模型，采用免疫组织化学染色法和Ｅｌｉｓａ法检测模型大鼠肺内ＶＥＧＦ的分布和含量变化。结果显示：低氧３周后大鼠形成明显的肺动脉高压；大鼠肺匀浆内ＶＥＧＦ含量在低氧３周组为４６６．９±７５．５ｐｇ／ｇ，明显高于对照组（３７６．２±４７．１ｐｇ／ｇ）；肺小动脉内膜的ＶＥＧＦ免疫组化染色阳性在低氧大鼠组明显增强。提示低氧在引起肺动脉高压的同时，可强烈刺激ＶＥＧＦ的合成和分泌，后者可能在低氧性肺血管重建过程中发挥重要的作用。     

慢性低氧对大鼠肺内血管内皮生长因子表达的影响

慢性低氧对大鼠肺内血管内皮生长因子表达的影响程德云陈文彬吴琦肖欣荣为了解血管内皮生长因子（ｖａｓｃｕｌａｒｅｎｄｏｔｈｅｌｉａｌｇｒｏｗｔｈｆａｃｔｏｒ，ＶＥＧＦ）在低氧性肺动脉高压发病中的可能作用，我们以慢性低氧复制大鼠肺动脉高压模型，观察其血清Ｖ...     

慢性低氧性肺动脉高压大鼠血清碱性成纤维细胞生长因子含量的 …

为探讨碱性成纤维细胞生长因子在慢性低氧性肺动脉高压肺血管重建中的作用及机理，采用慢性低氧性肺动脉高压大鼠模型，用酶联免疫吸附法测定其血清ｂＦＧＦ含量，并用原位杂交法观察肺、心、脑、肾等器官ｂＦＧＦｍＲＮＡ表达的变化。     

苏拉明对大鼠低氧性肺动脉高压的影响

目的 探讨血管内皮生长因子（ＶＥＧＦ）在低氧性肺动脉高压发病中的作用。方法 将３０只Ｗｉｓｔａｒ大鼠分为对照组、低氧组和低氧＋苏拉明组,以常压低氧复制大鼠肺动脉高压模型,采用微导管法测定肺动脉平均压,对肺组织切片进行图像分析。结果 经低氧３周后,大鼠形成明显的肺动脉高压、肺小动脉管壁增厚和在左心室肥厚;经苏拉明处理,可明显减轻低氧所致的肺动脉压升高、肺血管壁增厚和右心室肥厚。结论 慢性低氧导致肺动     

慢性低氧性肺动脉高压大鼠血清碱性成纤维细胞生长因子含量的变化

为探讨碱性成纤维细胞生长因子（ｂＦＧＦ）在慢性低氧性肺动脉高压肺血管重建中的作用及机理，采用慢性低氧性肺动脉高压大鼠模型，用酶联免疫吸附法测定其血清ｂＦＧＦ含量，并用原位杂交法观察肺、心、脑、肾等器官ｂＦＧＦｍＲＮＡ表达的变化。结果显示：低氧组血清ｂＦＧＦ含量（３５．９±２３．５ｐｇ．ｍｌ－１）明显高于对照组（６．３０±０．９７ｐｇ．ｍｌ－１，Ｐ＜０．００５）；低氧组肺小动脉ｂＦＧＦｍＲＮＡ表达明显增强，而心、脑、肾ｂＦＧＦｍＲＮＡ表达无变化。提示ｂＦＧＦ参与了慢性低氧性肺动脉高压肺小动脉重建的调控。     

血管内皮细胞生长因子与高原肺水肿发病的关系

目的 探讨血管内皮细胞生长因子（ＶＥＧＦ）表达变化在高原肺水肿发病、高原习服－适应中的意义。方法 培养大鼠肺动脉血管内皮细胞,采用ＲＴ－ＰＣＲ方法和酶联免疫吸附（ＥＬＩＳＡ）方法分别观察低氧（体积分数为１％的Ｏ２）细胞及培养液中ＶＥＧＦ表达变化;将大鼠分为５组,分别模拟不同海拔高度、不同时间进行间断低氧习服,每天４ｈ,间断低氧习服后的大鼠再进行急性低氧（８０００ｍ,４ｈ）。用免疫组织化学及ＲＮＡ狭缝杂交方法测定急性低氧和低氧习服不同时间、不同海拔高度大鼠肺组织ＶＥＧＦ变化,并对肺组织切片进行初步病理分析;采用ＥＬＬＳＡ方法测定大鼠、高原移居者及高原肺水肿患者治疗前后血浆中ＶＥＧＦ水平。结果 低氧时大鼠肺动脉血管内皮细胞ＶＥＧＦ表达水平明显升高（Ｐ〉０．０１）;低氧大鼠（包括急性低氧组及间断低氧习服组）血头及肺组     

内皮素受体拮抗剂对低氧性肺动脉高压的影响

为了探讨内皮素（ＥＴ）在低氧性肺动脉高压发病中的作用和评价ＥＴＡ受体拮抗剂的预防效应,将３０只Ｗｉｓｔａｒ大鼠分为对照组,低氧组和低氧＋ＢＱ－１２３组,以常压低氧复制大鼠动脉高压模型,采用微导管法测定肺动脉平均压、放射免疫法检测血浆ＥＴ－１含量对肺组织切片进行图象分析。结果发现：低氧３周后,大鼠形成明显的肺动脉高压,肺小动脉管壁增厚和右心室肥厚,ＷＴ％和ＷＡ％均明显升高,低氧大鼠血浆ＥＴ－１含量为     

bFGF mRNA在慢性低氧性肺动脉高压大鼠肺组织中的表达及分布

为探讨碱性成纤维细胞生长因子（ｂＦＧＦ）在慢性低氧性肺动脉高压肺血管重建中的作用及机理,通过建立慢性低氧性肺动脉高压大鼠模型,测定其肺血流动力学。并用酶联免疫吸附法（ＥＬＩＳＡ）测定肺组织匀浆ｂＦＧＦ含量,以及用原位杂交观察ｂＦＧＦｍＲＮＡ表达及分布变化。结果：①缺氧组肺组织匀浆ｂＦＧＦ含量为１８．６±２．９７Ｐｇ／ｍｌ,明显高于对照组（Ｐ＜０．００１）;②缺氧组肺小动脉ｂＦＧＦｍＲＮＡ表达明显增强。结果显示ｂＦＧＦ参与了慢性低氧性肺动脉高压肺小动脉重建的调控,其主要作用机理可能是自分泌或旁分泌形式     

常压低氧性肺动脉高压大鼠血中血小板激活因子水平的变化

为探讨血小板激活因子（ＰＡＦ）与低氧性肺动脉高压的关系，作者观测了１５只常压低氧性肺动脉高压大鼠模型的肺血流动力学指标及血中ＰＡＦ水平的变化。发现经低氧处理后，大鼠的肺动脉压、右心作功指数及血中ＰＡＦ水平升高，与对照组相比有明显差异，提高ＰＡＦ可能在低氧所致肺动脉高压的发病过程中发挥一定的作用。     

血管内皮生长因子在低氧性肺动脉高压大鼠肺内的分布和水 …

This study was designed to elucidate whether the level and distribution of vascular endothelial growth factor (VEGF) are changed in the lungs of rats with hypoxic pulmonary hypertension. 13 male Wistar rats were exposed to isobaric hypoxia for 3 weeks. The pulmonary artery pressure was measured by right cardiac catheterization. The level of VEGF in pulmonary homogenate was measured by Elisa method. The distribution of VEGF in the rat lung was examined by immunohistochemistry. The results showed that the pulmonary artery pressure was significantly increased after hypoxic exposure. The level of VEGF in pulmonary homogenate of rats treated with hypoxia (466.9 +/- 75.5 pg/g) were significantly increased as compared with taht of normal rats (376.2 +/- 47.1 pg/g). The contents of VEGF in the wall of pulmonary arteriole were significantly increased in rats with pulmonary hypertension. So we suggest that chronic hypoxia can strongly stimulate VEGF secretion, and VEGF may mediate the process of hypoxic pulmonary vascular remodeling and pulmonary hypertension.     

Effects of endothelin receptor antagonist on the hypoxic pulmonary hypertension]

This investigation was made to elucidate the role of endothelin (ET) in hypoxic pulmonary hypertension and the preventing effects of BQ-123, an ETA receptor antagonist. Thirty male Wistar rats were divided into three groups and exposed to air, isobaric hypoxia or isobaric hypoxia plus BQ-123 for 3 weeks. The pulmonary artery pressure was measured by right cardiac catheterization. The plasma level of ET-1 was measured by RIA method. Histologic sections of the lungs were examined by a computerized image analyser. In hypoxic rats, the pulmonary artery pressure and the thickness of wall of arteriole were significantly increased, and right ventricular hypertrophy was developed. The plasma level of VEGF in rats treated with hypoxia (192.3 +/- 43.1 pg/ml) was significantly increased as compared with that of normal rats (128.2 +/- 28.1 pg/ml), P < 0.01. Chronic BQ-123 treatment prevented the developments of pulmonary hypertension, thickening of pulmonary arteriole and right ventricular hypertrophy induced by hypoxia. These result indicate that chronic hypoxia can result in hypoxic pulmonary hypertension and increased plasma level of ET-1, and the ETA receptor antagonist can prevent hypoxic pulmonary hypertension.     

bFGFmRNA在慢性低氧性肺动脉高压大鼠肺组织中的表达及分布

为探讨碱性成纤维细胞生长因子在慢性低氧性肺动脉高压肺血管重建中的作用及机理,通过建立慢性低氧性动脉高压大鼠模型,测定其肺血流动力学 。     

Hypoxia-inducible factor-1 alpha regulates the role of vascular endothelial growth factor on pulmonary arteries of rats with hypoxia-induced pulmonary hypertension

Background Hypoxia-inducible factor-1α (HIF-1α) is one of the pivotal mediators in the response of lungs to decreased oxygen availability, and increasingly has been implicated in the pathogenesis of pulmonary hypertension. Vascular endothelial growth factor (VEGF), a downstream target gene of HIF-1α, plays an important role in the pathogenesis of hypoxic pulmonary hypertension and hypoxic pulmonary artery remodelling. In this study, we investigated the dynamic expression of HIF-1α and VEGF in pulmonary artery of rats with hypoxia-induced pulmonary hypertension. Methods Forty male Wistar rats were exposed to hypoxia for 0, 3, 7, 14 or 21 days. Mean pulmonary arterial pressure (mPAP), vessel morphometry and right ventricle hypertrophy index (RVHI) were estimated. Lungs were inflated and fixed for in situ hybridisation and immunohistochemistry. Results mPAP values were significantly higher than the control values after 7days of hypoxia ［(18.4±0.4) mmHg, P&lt;0.05］. RVHI developed significantly after 14 days of hypoxia. Expression of HIF-1α protein increased in pulmonary arterial tunica intima of all hypoxic rats. In pulmonary arterial tunica media, HIF-1α protein was markedly increased by day 3 (0.20±0.02, P&lt;0.05), reached the peak by day 7, then declined after day 14 of hypoxia. HIF-1α mRNA increased significantly after day 14 of hypoxia （0.20±0.02, P&lt;0.05）. VEGF protein began to increase markedly after day 7 of hypoxia, reaching its peak around day 14 of hypoxia (0.15±0.02, P&lt;0.05). VEGF mRNA began to increase after day 7 of hypoxia, then remained more or less stable from day 7 onwards. VEGF mRNA is located mainly in tunica intima and tunica media, whereas VEGF protein is located predominantly in tunica intima. Linear analysis showed that HIF-1α mRNA, VEGF and mPAP were correlated with hypoxic pulmonary artery remodelling. HIF-1α mRNA was positively correlated with VEGF mRNA and protein (P&lt;0.01). Conclusion HIF-1α and VEGF are both involved in the pathogenesis of hypoxia-induced pulmonary hypertension in rats.     

缺氧性肺动脉高压大鼠泡内肺动脉与右心室胶原表达及黄芪的干 …

目的 观察缺氧性肺动脉高压大鼠胞内肺动脉与右心室胶原表达及黄芪的干预作用,初步探讨其作用机制。方法 将雄性Ｗｉｓｔａｒ大鼠随机分为３组：（１）缺氧组：在常压缺氧舱内缺氧,每日１２小时,连续３周;（２）黄芪组：缺氧条件同缺氧组;自缺氧第一天起给大鼠每天腹腔注０．２ｍｌ黄芪注射液;（３）正常组对照组：室内空气正常饲养,用心导管和Ｆｉｃｋ’ｓ法测定肺动脉压和右心排血量,苦味酸天狼猩红染色切片观察泡内肺动     

低氧性肺动脉高压大鼠肺内 fractalkine 的变化

目的探讨趋化因子fractalkine在低氧性肺动脉高压发病机制中的作用。方法将20只雄性SD大鼠随机分为对照组和低氧组,每组10只,低氧组以常压低氧建立肺动脉高压模型。以右心导管法检测平均肺动脉压(mPAP),图像分析法测量肺小动脉壁厚度,计算出管壁厚度占血管外径的百分比(WT%)和管壁面积占血管总面积的百分比(WA%),逆转录-聚合酶链式反应(RT-PCR)法观察大鼠肺组织fractalkine mRNA的表达和酶联免疫法观察肺组织匀浆fractalkine的变化。结果对照组大鼠mPAP为(16.3±2.1)mmHg(1 mmHg=0.133 kPa),低氧组为(28.7±3.8)mmHg,两组比较差异具有统计学意义(P<0.01);对照组大鼠WT%为(10.20±1.56)%、WA%为(38.11±2.30)%,低氧组大鼠WA%和WT%分别为(21.28±4.60)%和(67.08±9.44)%,两组比较差异均具有统计学意义(P均<0.01);低氧组大鼠肺组织fractalkine mRNA的含量较对照组增加〔(0.49±0.05)vs(0.29±0.02),P<0.01〕,肺组织匀浆fractalkine浓度亦高于对照组〔(7622.6±938.4)pg/mL vs(4168.5±403.5)pg/mL,P<0.01〕。相关分析表明,fractalkine mRNA和蛋白与WA%和WT%均呈正相关(P<0.05)。结论慢性低氧大鼠肺组织fractalkine的合成和释放增多,fractalkine增加可能与低氧性肺动脉高压的发生有关。     

低氧大鼠肺组织核因子κB表达的变化

目的探讨核因子κB(NF-κB)在慢性低氧大鼠肺组织表达的变化及其在低氧性肺动脉高压发病中的作用。方法将20只雄性SD大鼠随机分为正常对照组和低氧组,以常压低氧3周复制肺动脉高压模型。采用微导管法测定大鼠平均肺动脉压(m PAP);对大鼠肺组织切片采用HE染色,经图像分析技术测定大鼠肺小动脉管壁厚度占血管外径的百分比(W T%)和管壁面积占血管总面积的百分比(W A%);采用免疫组化法检测两组大鼠肺组织NF-κB的表达情况。结果①低氧组大鼠m PAP为(29.1±4.5)mmHg,正常组大鼠m PAP为(16.8±2.6)mmHg,两组比较差异具有统计学意义(P<0.001);②低氧组大鼠W T%为(22.36±2.99)%、W A%为(69.14±5.38)%,正常对照组W T%为(13.30±2.77)%、W A%为(46.75±6.54)%,两组之间的差异有统计学意义(P均<0.01);③正常组和低氧组大鼠肺组织内均存在NF-κB阳性染色,以细支气管上皮细胞为明显,正常组大鼠NF-κB核染色阳性细胞百分比为(12.23±1.08)%,低氧组大鼠NF-κB核染色阳性细胞百分比为(29.11±1.12)%,两组比较差异有统计学意义(P<0.001)。结论NF-κB在慢性低氧大鼠肺内表达增加,可能参与了低氧性肺动脉高压的发病过程。     

THE ROLES OF bcl-2 GENE FAMILY IN THE PULMONARY ARTERY REMODELING OF HYPOXIA PULMONARY HYPERTENSION IN RATS

Objective. To investigate the roles of apeptosis in the pulmonary artery remodeling of pulmonary hypertension secondary to hypoxia and illustrate the relative genes expression. Methods. Thirty rats were divided into hypoxia group(10%O2, 8h/d) and normal control group. On the 15th day of hypoxia, pulmonary artery pressure and fight ventricular hypertrophy index were measured and pulmonary artery vessels were studied by light microscope. Then terminal deoxynucleotidyl transferase-mediateddUTP nick-end labeling(TUNEL)technique was used to detect nucleosomal DNA fragmentation of apeptotic cells.In situ hybridization and RT-PCR were used to detect the expression level of bel-2 and bax. Results. The pulmonary artery pressure and right ventricular hypertrophy index of hypoxia group were increased significantly, the pulmonary artery wall of hypoxic group become incrassate than control group. Apeptotic cells can be found in lung with hypoxia or without hypexia. Compared with control group, apeptotic index of hypoxic group decreased significantly. Through the methods of in situ hybridization and RT-PCR, we found the expression of bel-2 increased whereas bax decreased significantly in the hypoxic group. Conclusion. The alternation in bel-2 and bax expression induced by hypoxia play an important role in the pulmonary artery remodeling which is the main pathologic change of p~monary hypertension secondary to hypoxia.     

洛沙坦预防低氧性肺动脉高压的实验研究

目的 探讨血管紧张素Ⅱ受体拮抗剂洛沙坦对低氧性肺动脉高压的预防作用。方法 将30只Wistar大鼠分为对照组、低氧组和低＋洛沙坦组,以常压低氧建立大鼠肺动脉高压模型,采用微导管法测定平均肺动脉压,对肺组织切片进行图象分析。结果 经3周常压低氧处理后,低氧组大鼠形成了明显的肺动脉高压、肺小动脉管壁增厚和右心室肥厚;低氧＋洛沙坦处理组,其平均肺动脉压升高、肺血管壁增厚以及右心室肥厚程度均明显低于低氧组,P＜0.01。结论 血管紧张素和系统在低低氧性肺动脉高压发病过程中发挥重要的作用,洛沙坦对低氧性肺动脉高压具有明显的预防作用。