川芎嗪对大鼠慢性缺氧性肺动脉高压的保护作用及其与NOS基因表达的关系

以慢性常压缺氧的方法复制了大鼠慢性缺氧性肺动脉高压模型,观察了川芎嗪(LTZ80mg·kg~(-1),iP)对慢性缺氧性肺动脉高压的预防作用及cGMP含量(血浆和肺小动脉)和肺组织一氧化氮合成酶(NOS)基因的mRNA表达之变化.结果表明,慢性缺氧大鼠肺动脉平均压明显升高,但cGMP含量明显降低,肺组织NOS基因mRNA表达明显减弱;cGMP含量与肺动脉平均压呈明显负相关;LTZ对正常大鼠肺动脉压、cGMP含量和肺组织NOS基因的mRNA表达无明显影响,但可使慢性缺氧大鼠上述指标逆转.结果提示慢性缺氧大鼠肺组织NOS基因mRNA表达降低是慢性缺氧性肺动脉高压发病的机制之一,而LTZ增强了慢性缺氧大鼠肺NOS基因mRNA的表达可能是其预防慢性缺氧性肺动脉高压发生的重要机制.     

ING4、PHDs在低氧性肺动脉高压大鼠中的表达及意义分析

目的对低氧性肺动脉高压大鼠(HPH)中的ING4和PHDs的表达水平及其意义进行探讨。方法利用低氧性肺动脉高压大鼠模型,检测不同缺氧时间点上的大鼠右心室肥大指数(RVHI)、平均肺动脉压(m PAP)以及观察肺小动脉重塑(HPVR)。采用RT-PCR和Western blot检测ING4、PHDs以及HIF-1α的m RNA表达水平及蛋白表达水平。结果结果显示,从缺氧第7天开始实验组大鼠的m PAP显著高于空白对照组(P0.05),且第14天达到最高值,且大鼠的RVHI也开始增加,且已形成右心室肥厚和官腔狭窄。在m RNA水平上ING4、PHD2以及PHD3的表达在缺氧第3天开始显著增高(P0.05),且HIF-1α在起初无显著变化直到第14天才开始增高(P0.05),而PHD1的m RNA表达水平在缺氧后与空白对照组相比,无显著差异(P0.05);在蛋白水平上ING4的蛋白表达水平在缺氧第7天时表达显著增高(P0.05),PHD2、PHD3以及HIF-1α的蛋白表达水平在缺氧第3天开始增高(P0.05),而PHD1的蛋白表达水平在缺氧起初无显著变化,直到第14天时,与空白对照组比较,有显著降低,且随后一直维持较低水平(P0.05)。结论在低氧性肺动脉高压大鼠中ING4和PHDs的表达变化会影响低氧性肺动脉高压的产生和发展。     

夹竹桃麻素对高肺血流肺动脉高压大鼠的治疗作用

目的 观察夹竹桃麻素(apocynin)对肺高血流肺动脉高压大鼠肺动脉内皮细胞活性氧(ROS)及NADPH氧化酶4(NOX4)蛋白水平的影响,研究Apocynin对肺高血流肺动脉高压形成的拮抗作用.方法 将30只雄性SD大鼠随机均分为对照组、分流给药组、分流组,通过腹主动脉-下腔静脉分流法建立左向右分流肺高血流肺高压大鼠模型,测定大鼠平均肺动脉压、肺小动脉中膜厚度百分比(WT％)、肺小动脉管壁面积百分比(WA％);体外培养模型大鼠肺动脉内皮细胞,流式细胞仪检测2,7一二氢二氯荧光黄双乙酸钠(DCFH- DA)荧光探针标记的肺动脉内皮细胞活性氧水平,Western Blot法检测大鼠肺动脉内皮中NOX4蛋白的表达情况.结果 与分流组对比,分流给药组大鼠肺动脉压升高和肺血管重构情况明显改善,肺动脉内皮细胞中NOX4蛋白的表达较分流组虽无明显减少,但细胞内ROS的水平显著下降.结论 持续使用夹竹桃麻素干预,可使左向右分流肺动脉高压大鼠肺动脉内皮细胞中ROS水平明显下降,从而拮抗大鼠肺动脉高压的形成.     

Rho激酶在肺动脉高压大鼠肺组织中的表达

目的探讨Rho激酶在肺动脉高压大鼠肺组织中的表达及其作用机制。方法48只雄性SD大鼠,随机分为对照组和模型组,测大鼠平均肺动脉压力(mPAP)、右心室肥厚指数(RVHI)。采用RT-PCR及Western blot法,从基因和蛋白水平观察肺组织Rho激酶表达;Western blot法检测其底物肌球蛋白磷酸酶的磷酸化状态,作为该激酶功能活化标志。结果Rho激酶mRNA和蛋白在肺动脉高压早期即明显上调,后期仍维持于较高水平;肌球蛋白磷酸酶磷酸化水平也较对照组显著增高(P均<0.01),并与mPAP及RVHI均呈显著正相关(P均<0.01)。结论肺动脉高压大鼠肺组织中存在Rho激酶的表达上调与功能活化,提示Rho激酶在肺动脉高压发病机制中具有重要作用。     

黄芪多糖对野百合碱诱导大鼠肺动脉高压的减缓作用及其机制研究

目的研究黄芪多糖对野百合碱诱导大鼠肺动脉高压的减缓作用及可能机制。方法将100只SD雄性大鼠随机分为正常对照组、野百合碱组、黄芪多糖低剂量组和黄芪多糖高剂量组。除正常对照组外,其余组大鼠按60 mg/kg单次腹腔注射野百合碱。黄芪多糖低剂量组及高剂量组大鼠在给药后的第2~28天分别按200 mg/kg及400 mg/kg腹腔注射黄芪多糖,每日1次。每组25只大鼠各取15只进行研究,检测各组大鼠平均肺动脉压(mPAP)、右心肥厚指数(RVHI),观察其肺动脉及心肌细胞形态变化,检测其肺组织中白细胞介素17(IL-17)mRNA及蛋白的表达水平。结果与正常对照组比较,野百合碱组及黄芪多糖各剂量组大鼠mPAP、RVHI均显著升高(P<0.01),肺组织中IL-17的mRNA和蛋白表达水平均显著升高(P<0.01),肺动脉及心肌细胞有明显病理改变;与野百合碱组比较,黄芪多糖各剂量组大鼠mPAP、RVHI均显著降低(P<0.01),肺组织中IL-17的mRNA和蛋白表达水平均显著降低(P<0.01),肺动脉及心肌细胞病理变化有改善;与黄芪多糖低剂量组比较,黄芪多糖高剂量组大鼠上述指标水平及病理改变的改善更明显。结论黄芪多糖能降低野百合碱诱导大鼠的肺动脉高压,并改善肺动脉结构及心肌病理改变,推测其机制可能与下调大鼠肺组织中IL-17的表达有关。     

野百合碱诱导的肺动脉高压大鼠肺血管5-HT转载体表达增强

目的　研究野百合碱诱导的大鼠肺动脉高压与5 HT转载体基因表达的关系。方法　应用MCT诱导的慢性肺动脉高压大鼠模型,建立离体动脉环5 HT浓度反应曲线;HE染色观察肺动脉构型重建,应用RT PCR检测大鼠肺动脉5 HT转载体mRNA表达。结果　MCT大鼠肺血管对5 HT收缩反应增强,肺肌型小动脉中膜增厚,MCT诱导的肺动脉高压大鼠肺血管5 HT转载体mRNA表达明显增多。5 HT转载体基因表达与肺肌型小动脉中膜增厚有明显相关性。结论　MCT诱导的肺动脉高压大鼠肺血管构型重建及5 HT引起收缩反应增强,伴有5 HT转载体mRNA表达增多;同时5 HT转载体mRNA表达与肺肌型小动脉中膜增厚有明显相关性,提示5 HT转载体可能在肺动脉高压中起重要作用。     

β肾上腺素对大鼠急性肺动脉梗塞时肺脏水清除率的影响

目的探讨β肾上腺素对大鼠急性肺动脉栓塞时急性肺损伤的肺脏水清除率的影响。方法 30只SPF级SD大鼠,随机分为对照组、急性肺动脉梗阻4 h和24 h组,每组10只,建立大鼠左肺的急性肺动脉阻塞模型。分别测定左右肺的肺水容量、肺水清除率(AFC),应用β肾上腺素受体激动剂和抑制剂进一步调节发生变化的AFC,Real-time PCR方法测定β2肾上腺受体蛋白mRNA在大鼠肺组织中的表达。结果急性肺动脉阻塞4 h和24 h组的左肺AFC明显升高,肺动脉阻塞24 h后,肺水容量上升。但保持血液灌流的右肺无明显变化。β肾上腺素激动剂Terbutaline调节阻塞的左肺,各组AFC升高不明显,但β肾上腺素抑制剂propranolol可降低各组已经升高的肺水清除率。Real time PCR证实,4 h组和24 h组左肺β肾上腺素受体的mRNA水平升高。结论急性肺动脉栓塞可以引起大鼠阻塞肺肺水清除率的变化,在4 h升至顶峰,24 h略有下降。AFC的升高可能与β肾上腺素受体激活有关。     

慢性低氧性肺动脉高压大鼠肺动脉NO和肺组织eNOS蛋白表达的变化

为观察内皮型一氧化氮合酶（eNOS）/一氧化氮（NO）体系在大鼠慢性低氧性肺动脉高压发生发展中的代谢变化,将50只Wistar雄性成年大鼠随机分为常氧组（N组）、低氧7天组（H7 d组）、低氧14天组（H14 d组）、低氧21天组（H21 d组）和低氧28天组（H28 d组）,每组10只。通过建立慢性低氧性肺动脉高压模型,观察各组大鼠平均肺动脉压（mPAP）、平均颈动脉压（mCAP）、右心室肥大指数、肺动脉血NO含量,以及肺组织中eNOS蛋白的变化。结果表明,H14 d、H21 d及H28 d组mPAP较N组明显增加（P〈0.01）;H28 d组和H21 d组RV/（LV＋S）明显高于N组（P〈0.05）;肺动脉血中NO水平,在H14 d组、H21 d组和H28 d组较N组明显增加（P〈0.01）;H21 d组和H28 d组肺组织eNOS蛋白含量明显高于N组（P〈0.01）。结论：慢性低氧性肺动脉高压的发病与NO生物合成障碍有关。慢性缺氧时,eNOS表达水平呈上调趋势,然而与其相应的NO含量却降低,其可能的机制为eNOS/NO体系功能障碍,其中eNOS质的缺陷是内源性NO代谢障碍及NO生成不足的主要原因。     

辛伐他汀对野百合碱诱导的肺动脉高压大鼠IL-6和IL-8表达的影响

目的观察辛伐他汀对野百合碱（MCT）诱导的肺动脉高压大鼠炎症细胞因子IL-6和IL-8表达的影响,探讨辛伐他汀作用于肺动脉高压的机制。方法将30只健康雄性SD大鼠随机平均分为正常对照组、MCT诱导的肺动脉高压组（模型对照组）、辛伐他汀干预治疗组（治疗组）。模型对照组和治疗组注射野百合碱造模。治疗21 d后,采用右心导管法检测大鼠平均肺动脉压（mPAP）;称量RV和LV＋S,计算右心肥大指数（RVHI）。采用RT-PCR检测大鼠肺组织中IL-6和IL-8 mRNA的表达,采用ELISA法检测大鼠血清中IL-6和IL-8水平。结果模型对照组mPAP和RVHI值显著高于治疗组和正常对照组,治疗组和正常对照组mPAP和RVHI值比较无显著性差异。模型对照组大鼠肺组织中IL-6和IL-8 mRNA的表达和血清中IL-6和IL-8水平显著高于正常对照组和治疗组,而治疗组大鼠肺组织中IL-6和IL-8 mRNA的表达和血清中IL-6水平与正常对照组比较无显著性差异,但治疗组大鼠血清IL-8水平高于正常对照组（P〈0.05）。结论辛伐他汀可通过抑制MCT诱导大鼠肺动脉高压模型大鼠肺组织中炎性细胞因子的表达、下调大鼠炎性细胞因子的分泌,达到对肺动脉高压的治疗作用。     

盆炎康合剂对慢性盆腔炎大鼠盆腔粘连及TGF-β1 mRNA表达的影响

目的 研究盆炎康合剂对慢性盆腔炎大鼠TGF-β1mRNA表达的影响及与盆腔粘连程度的关系.方法 造模大鼠随机分为5组,分别于给药第14天、21天、28天观察各组大鼠盆腔粘连程度,用荧光定量PCR方法进行TGF-β1mRNA水平的检测.结果 给药第21天、第28天后,模型组TGF-β1mRNA与正常组比较均显著升高(P＜0.01),而盆炎康高、中剂量组与模型组比较也均有非常显著性差异(均为P＜0.01).给药第14天、第21天后,中剂量组和高剂量组的盆腔粘连程度分别与模型组比较,均具有显著性差异(P＜0.05).给药第28天后,高剂量组的盆腔粘连程度与模型组比较,具有显著性差异(P＜0.05).结论 盆炎康合剂高、中剂量组能明显下调慢性盆腔炎大鼠TGF-β1mRNA表达水平,改善盆腔粘连程度.     

松龄血脉康抑制肺动脉高压的实验研究

为观察松龄血脉康胶囊对肺动脉高压大鼠肺动脉压的影响，取１００只健康Ｗｉｓｔａｒ大鼠，其中６０只背部注射野百合碱ｍｏｎｏｃｒｏｔａｌｉｎｅ，ＭＣＴ８０ｍｇ／ｋｇ复制出肺动脉高压模型。再将其分为两组，各３０只，其中一组以标准饲料喂养，另一组加用松龄血脉康胶囊１．５ｇ·ｋｇ－１·ｄ－１。其余４０只健康大鼠做为正常对照组，在实验当天、７天、１４天、２１天、２８天、３５天从各组中随机抽取５只行右心导管测肺动脉压。结果：注射ＭＣＴ后肺高压组２８天时达高峰，但加用松龄血脉康组上升幅度明显小于未用药组。结论：松龄血脉康有显著抑制大鼠肺动脉高压发展的作用     

Downregulation of osteopontin is associated with fluoxetine amelioration of monocrotaline-induced pulmonary inflammation and vascular remodelling

1. Osteopontin (OPN) has emerged as a key factor in inflammatory activation and cardiovascular remodelling. The aim of the present study was to investigate the involvement of OPN in fluoxetine amelioration of monocrotaline (MCT)-induced pulmonary inflammation and vascular remodelling in rats. 2. Wistar rats were divided into control, MCT and two fluoxetine-treated groups. Pulmonary arterial hypertension (PAH) was induced by a single injection of MCT (60 mg/kg, i.p.). Fluoxetine (2 and 10 mg/kg) was administered via the intragastric route once a day for 21 days. On Day 22, pulmonary haemodynamic measurements were undertaken, followed by ELISA, western blotting and immunohistochemistry. 3. Monocrotaline caused pulmonary inflammation and vascular remodelling and significantly enhanced OPN expression in the plasma, lungs and pulmonary arteries. Fluoxetine decreased pulmonary arterial pressure and ameliorated pulmonary inflammation and pulmonary vascular remodelling. At 10 mg/kg, fluoxetine significantly inhibited MCT-induced increases in the expression of serotonin transporter (SERT) and phosphorylated extracellular signal-regulated kinase 1/2 and downregulated the expression of OPN, macrophage inflammatory protein-1β and matrix metalloproteinase 2/tissue inhibitor of metalloproteinase 2. Although 2 mg/kg fluoxetine tended to ameliorate some MCT-induced changes in the lung, the differences did not always reach statistical significance. Linear regression analysis showed that there was a positive correlation between plasma OPN concentrations and mean pulmonary arterial pressure, as well as percentage medial wall thickness and percentage wall area in the pulmonary artery. 4. In conclusion, the amelioration by fluoxetine of MCT-induced pulmonary inflammation and vascular remodelling is associated with downregulation of OPN expression in rats.     

Acute vasodilator effect of fasudil, a Rho-kinase inhibitor, in monocrotaline-induced pulmonary hypertension in rats

Pulmonary arterial hypertension is a progressive and fatal disease for which Rho-kinase may be substantially involved. In this study, we examined the acute vasodilator effects of fasudil, a Rho-kinase inhibitor, in monocrotaline (MCT)-induced pulmonary hypertension (PH) in rats. Three weeks after a single subcutaneous injection of MCT (60 mg/kg), hemodynamic variables were measured under conscious and free-moving conditions before and after oral administration of fasudil. MCT caused a significant elevation of mean pulmonary arterial pressure (mPAP). Although a low dose of fasudil (3 mg/kg) had no effect on mPAP, a middle dose (10 mg/kg) caused a significant reduction in mPAP without change in mean systemic arterial pressure (mSAP), and a high dose (30 mg/kg) significantly reduced both mPAP and mSAP. Rho-kinase activity was significantly increased by MCT injection in pulmonary arteries but not in the aorta. Fasudil (10 mg/kg) inhibited only the Rho-kinase activity in pulmonary arteries without any effect in the aorta. Plasma concentration of hydroxyfasudil, a metabolite of fasudil, was within its clinical range in humans. These results demonstrate that fasudil exerts effective and selective vasodilatation of pulmonary arteries in rats with MCT-induced PH at a given dose, suggesting its usefulness for the treatment of the fatal disorder.     

Tachykinin dysfunction attenuates monocrotaline-induced pulmonary hypertension

We explored the dysfunction of tachykinins on monocrotaline (MCT)-induced pulmonary hypertension by using double-stranded preprotachykinin (ds PPT) RNA and neurokinin receptor (NK) antagonists. Here, we showed the possibility to attenuate the PPT gene expression by ds RNA, RNA interference (RNAi), in fully developed tissue of rats. We designed four groups (control, MCT, RNAi + MCT, and solvent + MCT) of experiments in series 1 and seven groups (control, MCT, MCT + CP-96345-3.4, MCT + CP-96345-10, MCT + CP-96344-10, MCT + SR-48968, and MCT + SR-48965) of experiments in series 2. Rats in the control groups received saline injection. MCT-treated rats received a single MCT injection (60 mg/kg sc). One day prior to MCT, bilateral nodose ganglia were microinjected with ds PPT RNA in rats of the RNAi + MCT group or with solvent in the solvent + MCT group. Beginning from 1 day post-MCT, MCT-treated rats received a daily injection of the NK(1) receptor antagonist, CP-96345 (3.4 or 10 mg/kg ip) or its inactive enantiomer CP-96344 (10 mg/kg ip). The NK(2) receptor antagonist SR-48968 (3 mg/kg ip) or its inactive enantiomer SR-48965 (3 mg/kg ip) was injected to MCT-treated rats every other day starting 1 day post-MCT. Functional study was carried out 2 weeks (series 1) or 3 weeks (series 2) after MCT. MCT induced right ventricular hypertrophy, as well as increases in pulmonary arterial pressure, PPT mRNA (nodose ganglia and lung tissue), and lung tissue substance P level. All of the above MCT-induced alterations were attenuated by either RNAi or NK receptor antagonists. We conclude that tachykinins play an important role in MCT-induced pulmonary hypertension.     

舍曲林和氟西汀对慢性肺动脉高压模型大鼠的保护作用研究

目的:研究选择性5-羟色胺重吸收抑制剂(SSRI)舍曲林和氟西汀对野百合碱(MCT)诱导的慢性肺动脉高压(PAH)大鼠的保护作用。方法:40只大鼠随机分为对照组、MCT组、MCT+舍曲林(MCT+Ser)组和MCT+氟西汀(MCT+Flu)组,后3组大鼠腹腔注射MCT造模。MCT+Ser组和MCT+Flu组大鼠每天分别给予Ser和Flu,MCT组和对照组大鼠给予相应溶剂。各组大鼠常规饲养3周后检测肺动脉压、右心指数;HE染色法测定并计算非肌型动脉、部分肌型动脉及肌型动脉所占比例,比较各组肺动脉肌化程度;逆转录-聚合酶链反应法测定5-羟色胺转运体(SERT)mRNA表达变化。结果:与对照组比较,MCT组肺动脉压、右心指数、动脉肌化程度及SERTmRNA表达升高;与MCT组比较,MCT+Ser组和MCT+Flu组上述各指标均降低(P<0.05或P<0.01)。结论:Ser和Flu对MCT诱导的PAH具有抑制作用,作用机制可能与抑制SERTmRNA表达有关。     

Estradiol metabolites attenuate monocrotaline-induced pulmonary hypertension in rats

Pulmonary arterial hypertension (PH) is a deadly disease characterized by pulmonary arterial vasoconstriction and hypertension, pulmonary vasculature remodeling, and right ventricular hypertrophy. Our previous in vivo studies, performed in several models of cardiac, vascular, and/or renal injury, suggest that the metabolites of 17beta-estradiol may inhibit vascular and cardiac remodeling. The goal of this study was to determine whether 2-methoxyestradiol (2ME), major non-estrogenic estradiol metabolite, prevents the development and/or retards the progression of monocrotaline (MCT)-induced PH. First, a total of 27 male Sprague Dawley rats were injected with distillated water (Cont, n=6) or monocrotaline (MCT; 60 mg/kg, i.p.; n=21). Subsets of MCT animals (n=7 per group) received 2ME or its metabolic precursor 2-hydroxyestradiol (2HE; 10 microg/kg/h via osmotic minipumps) for 21 days. Next, an additional set (n=24) of control and MCT rats was monitored for 28 days, before right ventricular peak systolic pressure (RVPSP) was measured. Some pulmonary hypertensive animals (n=8) were treated with 2ME (10 microg/kg/h) beginning from day 14 after MCT administration. MCT caused pulmonary hypertension (ie, increased right ventricle/left ventricle+septum [RV/LV+S] ratio and wall thickness of small-sized pulmonary arteries, and elevated RVPSP) and produced high and late (days 22 to 27) mortality. Pulmonary hypertension was associated with strong proliferative response (PCNA staining) and marked inflammation (ED1+cells) in lungs. Both metabolites significantly attenuated the RV/LV+S ratio and pulmonary arteries media hypertrophy and reduced proliferative and inflammatory responses in the lungs. Furthermore, in diseased animals, 2ME (given from day 14 to 28) significantly decreased RVPSP, RV/LV+S ratio and wall thickness, and reduced mortality by 80% (mortality rate: 62.5% vs. 12.5%, MCT vs. MCT+2ME day 14 to 28). This study provides the first evidence that 2ME, a major non-estrogenic, non-carcinogenic metabolite of estradiol, prevents the development and retards the progression of monocrotaline-induced pulmonary hypertension. Further evaluation of 2ME for management of pulmonary arterial hypertension is warranted.     

野百合碱诱导大鼠肺动脉高压动物模型的制备

目的采用注射野百合碱(MCT)制备大鼠肺动脉高压模型,并对肺动脉压测定方法进行优化。方法通过ip MCT诱导建立大鼠肺动脉高压模型,通过测定大鼠肺血管阻力的方法来对大鼠右心室压进行测定,采用阳性药对照、血流动力学测定和组织学观察确定模型是否建立成功。结果 ip 50 mg/kg MCT 4周后大鼠右心室平均压、右心肥大指数对比对照组明显增高,观察病理组织切片,可见明显的内皮细胞损伤,分布不均,动脉管壁明显增厚,肺组织有大量的炎性细胞浸润,出现肺血管的重构,证实肺动脉高压动物模型造模成功。结论采用ip MCT可以建立稳定的大鼠肺动脉高压模型,且具有较高的存活率,同时建议采用改良的心导管测定方法测定大鼠右心室压力。     

Amlodipine prevents monocrotaline-induced pulmonary arterial hypertension and prolongs survival in rats independent of blood pressure lowering

1. The present study was designed to examine the role of amlodipine in preventing and reversing monocrotaline (MCT)-induced pulmonary arterial hypertension (PAH) in rats. 2. Rats were injected with MCT (40 mg/kg, s.c.) and randomly given either 6 mg/kg per day of amlodipine in drinking water or placebo for 3 weeks. Any animals treated with MCT that survived for 3 weeks were given either amlodipine or placebo for the next 3 weeks. 3. Blood pressure was not different between the groups. Amlodipine immediately following MCT markedly inhibited PAH with severe pulmonary vascular remodelling. The survival rate at 3 weeks after treatment was increased significantly in the amlodipine group compared with the placebo group (77%vs 43%; P < 0.01). The placebo group showed markedly diminished expression of endothelial nitric oxide synthase (eNOS) protein and mRNA levels, increased numbers of proliferating cell nuclear antigen-positive cells, enhanced mRNA expression of matrix metalloproteinase-2 and pro-inflammatory cytokines in the lung tissue and upregulation of P-selectin on the endothelium of the pulmonary arteries, whereas these effects were suppressed in the amlodipine-treated group. Furthermore, late treatment with amlodipine did not palliate PAH or improve survival. 4. Amlodipine inhibited the development of PAH and improved survival in rats independent of its effect on lowering blood pressure. These effects were associated with marked inhibition of the downregulation of eNOS and improvement of pulmonary vascular endothelial activation, as well as anti-inflammatory, antiproliferative and antifibrotic effects in the lung tissue. However, amlodipine failed to reverse established PAH. This study may provide an insight into therapeutic strategy of amlodipine in PAH.     

尼群地平对大鼠野百合碱性肺动脉高压的防治作用

目的：利用野百合碱（ＭＣＴ）引起的大鼠肺动脉高压（ＰＨ）模型，探讨尼群地平（ＮＩＴ）对ＭＣＴ性ＰＨ的防治作用。方法：给ＭＣＴ或ＭＣＴ＋ＮＩＴ（１０ｍｇ·ｋｇ－１ｉｐ，每日一次）４ｗｋ，测定肺血流动力学参数和静脉血浆及肺组织匀浆中内皮素样免疫反应物（ｉｒ－ＥＴ）、一氧化氮（ＮＯ）、超氧化物歧化酶（ＳＯＤ）和丙二醛（ＭＤＡ）的含量。结果：ＮＩＴ能有效地降低ＭＣＴ模型大鼠的肺动脉压（从４．５±０．９降至３．６±０．５ｋＰａ）和肺血管阻力（从１１８±１７降至７９±１８ｋＰａ·ｍｉｎ·Ｌ－１），能抑制ＭＣＴ引起的肺小动脉中膜增厚；ＮＩＴ能显著抑制ＭＣＴ模型大鼠的肺组织匀浆中ＮＯ含量的减少和血浆中ＳＯＤ活性的降低（Ｐ＜０．０５），明显阻止肺匀浆中ＭＤＡ的升高（Ｐ＜０．０１）。结论：长期使用ＮＩＴ可有效防治ＭＣＴ性ＰＨ，其作用可能与其Ｃａ２＋拮抗作用及保护ＳＯＤ活性和增加ＮＯ含量有关。