染料木黄酮对慢性缺氧性肺血管结构改建的干预作用

目的　探讨染料木黄酮对大鼠缺氧性肺血管结构改建的干预作用及其作用机制。方法　将♂Wistar大鼠随机分为 3组 ,常氧对照组 (C)、慢性缺氧组 (H)和慢性缺氧 +染料木黄酮组 (H +G) ,对肺血管进行显微形态学观察。通过免疫组织化学方法检测肺动脉平滑肌细胞增殖细胞核抗原(PCNA)的表达。结果　与常氧对照组相比 ,慢性缺氧组大鼠肺血管管壁增厚 ,管腔狭窄 ,肌型动脉百分比显著增加 (P<0 .0 1) ;肺动脉平滑肌增殖细胞核抗原表达增加。与H组比较 ,H +G组大鼠肺动脉管壁增厚程度及血管腔狭窄程度显著减轻 ,肌型动脉百分比显著降低 (P <0 0 1) ;肺动脉平滑肌PCNA表达明显减少。结论　实验结果提示 ,染料木黄酮可以显著抑制缺氧性肺血管结构改建 ,其作用机制可能与其抑制缺氧诱导的肺动脉平滑肌细胞增殖有关。     

三七皂甙对慢性缺氧性肺动脉高压的影响

目的：研究三七皂甙对大鼠慢性缺氧性肺动脉高压的作用。方法：采用间断常压缺氧法制备大鼠慢性缺氧性肺动脉高压模型，腹腔注射三七皂甙（２５，５０和１００ｍｇ·ｋｇ－１·ｄ－１），连续给药２１天。结果：三七皂甙能产生剂量依赖性地抑制慢性缺氧性肺动脉高压的作用，其抑制率分别为１５．９％、４３．９％和７３．４％，并能明显抑制右心室肥厚，其抑制率分别为２２．１％、５５．６％和８３．３％，而对颈动脉血压无明显的影响。三七皂甙（２００ｇ·Ｌ－１）能明显抑制血小板生长因子所诱导的离体肺动脉平滑肌细胞ＤＮＡ的合成。结论：三七皂甙有抑制慢性缺氧性肺动脉高压的作用，可能是通过抑制血小板生长因子促肺动脉平滑肌细胞增殖而抑制肺血管结构重建来实现的。     

植物雌激素大豆苷原(daidzein)对结肠癌LoVo细胞生长的影响

目的　了解植物雌激素大豆苷原(daidzein)对结肠癌细胞生长的影响。方法　取对数生长期的人结肠癌细胞株LoVo细胞,以不同浓度的大豆苷原处理细胞2 ,3,4和6d ,然后应用MTT法测定细胞的生长率。结果　大豆苷原在高浓度10 0 μmol/L时在体外对LoVo有明显的抑制作用(P<0.01) ,而在低浓度<5 μmol/L时对LoVo细胞又具有促增殖作用。结论　大豆苷原在体外对LoVo细胞的生长具有促进和抑制的双向作用     

Losartan对大鼠慢性低氧性肺动脉高压的影响

目的：观察Ｌｏｓａｒｔａｎ对慢性动脉高压大鼠肺动脉、颈动脉压及右心室肥厚的影响。方法：将雄性Ｗｉｓｔａｒ大鼠２４只随机分３组,每组８只,正常组置于常氧状态下饲养,对照组及治疗组坟间隙缺氧法缺氧,治疗组每日用管饲法喂Ｌｏｓａｒｔａｎ５ｍｇ／只,结果：氧４周后,对照组平均肺动脉压及相中心室较正常显著升高,治疗组ｍＰＡＰ及相对右心室重量较姐显著下降,而３组大鼠颈内动脉血压均无明显变化。结果：Ｌｏｓａｒｔ     

植物雌激素大豆苷原(daidzein)对结肠癌LoVo细胞生长的影响

目的 了解植物雌激素大豆苷原(daidzein)对结肠癌细胞生长的影响。方法 取对数生长期的人结肠癌细胞株LoVo细胞,以不同浓度的大豆苷原处理细胞2,3,4和6d,然后应用MTT法测定细胞的生长率。结果 大豆苷原在高浓度100μmol/L时在体外对LoVo有明显的抑制作用(P＜0．01),而在低浓度＜5μmol/L时对LoVo细胞又具有促增殖作用。结论 大豆苷原在体外对LoVo细胞的生长具有促进和抑制的双向作用。     

尼群地平对缺氧性右心室肥大的预防和治疗作用

目的：本文探讨尼群地平对缺氧性右心室肥大的影响。方法：慢性间断性减压引起缺氧性右心室肥大，用右心室重量指数，心肌超微结构变化来评价尼群地平疗效。结果：慢性缺氧大鼠右心室收缩压及右心室重量指数明显增加及心肌超微结构变化，无论在减压开始或已发展右心室肥大后，服用尼群地平平均可降低右室收缩压和右室重量指数及促使心肌超微结构正常，结果：尼群地平可预防和减轻缺氧性右心室肥大。     

尼群地平对缺氧性右心室肥大的预防和治疗作用(英文)

目的:本文探讨尼群地平对缺氧性右心室肥大的影响。方法:慢性间断性减压引起缺氧性右心室肥大,用右心室重量指数,心肌超微结构变化来评价尼群地平疗效。结果:慢性缺氧大鼠右心室收缩压及右心室重量指数明显增加及心肌超微结构变化。无论在减压开始或已发展右心室肥大后,服用尼群地平均可降低右室收缩压和右室重量指数及促使心肌超微结构正常。结论:尼群地平可预防和减轻缺氧性右心室肥大。     

川芎嗪对慢性缺氧高二氧化碳大鼠肺动脉高压的影响

研究川芎嗪对大鼠慢性缺氧、慢性缺氧伴高二氧化碳所致肺动脉高压的作用及对心肌力学指标和动脉血氧分压的影响。结果表明，川芎嗪（ＴＭＰＺ）８０ｍｇ·ｋｇ－１能显著抑制由慢性缺氧、慢性缺氧伴高二氧化碳所致肺动脉升压反应及右心室收缩压，而对右心室ＲＶ±ｄＰ／ｄｔｍａｘ、动脉血氧分压都无明显影响。提示川芎嗪能降低慢性缺氧高二氧化碳大鼠的肺动脉压力，而不降低动脉血氧分压，且对右心功能具有保护作用，是一种降低慢性阻塞性肺部疾病肺动脉高压的理想药物。     

植物雌激素的化学分类和药理作用

植物雌激素广泛存在于植物中,化学结构上大致分为异黄酮类、香豆素类、木脂素类、查耳酮类等,在治疗乳腺癌、前列腺癌、心血管疾病、绝经症状、骨质疏松症和改善认知能力方面已有确切的疗效和应用。概述了有关植物雌激素的分类和药理作用研究最新进展。     

植物雌激素对乳腺和前列腺癌的作用

天然存在于一些植物食物内的植物雌激素是激素样化合物，结构上类似于雌性激素。英国Ulster大学的研究人员对植物雌激素对乳腺和前列腺癌的体内和体外作用进行了考察，并讨论了这些化合物可能的作用机理。两类主要的植物雌激素是大多存在于大豆中的异黄酮和存在于亚麻仁、谷类作物、水果和浆果中的木脂体。     

中介素在低氧性肺动脉高压大鼠中的变化和意义

目的 观察比较中介素在低氧性肺动脉高压大鼠血浆和支气管肺泡灌洗液含量的变化.方法 雄性Wistar大鼠被随机分为4组,对照组、低氧1周组、2周组、3周组.利用放免分析法测定大鼠血浆和支气管肺泡灌洗液的含量.结果 低氧组大鼠血浆和支气管肺泡灌洗液中介素含量明显高于对照组.同时支气管肺泡灌洗液和血浆的变化趋势一致.结论 中介素血浆和支气管肺泡灌洗液含量增高,提示机体可能对缺氧性肺动脉高压起到一定的缓冲和保护作用.     

Protective effects of vasonatrin peptide against hypobaric hypoxia-induced pulmonary hypertension in rats

1. The aim of the present study was to investigate the in vivo effects of vasonatrin peptide (VNP) on hypoxia-induced pulmonary hypertension (HPH).
2. The HPH model was developed by subjecting rats to hypobaric hypoxia. The HPH rats were then treated with either VNP (50 μg/kg per day, i.p.) or saline (0.5 mL, i.p.) every day for 7 days. Haemodynamic indices, right ventricular hypertrophy (RVH) and remodelling of the pulmonary arteries were evaluated. In addition, plasma levels of atrial natriuretic peptide (ANP), endothelin (ET)-1 and angiotensin II (AngII) were determined, as was natriuretic peptide receptor-C (NPR-C) mRNA expression in the right ventricle.
3. Hypobaric hypoxia induced severe HPH compared with the normoxic control group. Treatment of HPH rats with VNP for 1 week significantly reduced mean pulmonary arterial pressure, pulmonary vascular resistance, RVH and muscularization of the pulmonary arteries, although pulmonary blood flow was increased in this group. In addition, significantly lower levels of plasma ET-1 and AngII and cardiac NPR-C mRNA expression were observed in VNP-treated compared with saline-treated HPH rats, whereas higher plasma concentrations of ANP were found in the former group. Acute intravenous administration of 50 μg/kg VNP significantly ameliorated pulmonary haemodynamics in HPH rats.
4. Taken together, the date indicate that VNP has certain preventative and therapeutic effects against HPH.     

黄芪总皂苷对缺氧性肺动脉高压作用探讨

目的　探讨黄芪总皂苷（AST）对缺氧性肺动脉高压（HPH）病理进展的抑制作用及相关机制。方法　28只SPF级雄性SD大鼠随机分为对照组、HPH组、HPH+AST15［15 mg/（kg·d）］组、HPH+AST45［45 mg/（kg·d）］组,每组7只。采用间断式常压低氧建立大鼠HPH模型。实验28 d后,检测大鼠右心室收缩压力（RVSP）;计算右心室（RV）和左心室+室间隔（LV+S）的比值RV/（LV+S）;HE染色及免疫荧光染色观察大鼠肺动脉结构重建,计算肺动脉厚度百分比（WT）、面积百分比（WA）,并测量肺动脉α-平滑肌肌动蛋白（α-SMA）的光密度（OD）值;分光光度法检测大鼠肺组织及血清中的超氧化物歧化酶（SOD）、过氧化氢酶（CAT）及丙二醛（MDA）水平;Western blot法检测大鼠肺组织中还原型烟酰胺腺嘌呤二核苷酸磷酸（NADPH）氧化酶Nox2和Nox4蛋白表达情况。结果　与对照组比较,HPH组大鼠RVSP、RV/（LV+S）、WT、WA、α-SMA均增高（P＜0.05）,肺组织及血清中的SOD、CAT水平明显降低,而MDA水平增高（P＜0.05）,肺组织中Nox2和Nox4蛋白表达水平升高（P＜0.05）。与HPH组比较,HPH+AST15组和HPH+AST45组大鼠RVSP、RV/（LV+S）、WT、WA、α-SMA均降低（P＜0.05）,肺组织及血清中的SOD、CAT水平升高,MDA水平降低（P＜0.05）,肺组织中Nox2和Nox4蛋白表达水平均降低（P＜0.05）,其中HPH+AST45组WT、WA、α-SMA及肺组织MDA水平、Nox2和Nox4蛋白表达水平均较HPH+AST15组更低（P＜0.05）。结论　黄芪总皂苷可抑制大鼠HPH的病理进展,其机制可能与提高大鼠体内SOD和CAT水平并抑制Nox2和Nox4表达有关。     

Thromboxane receptor hyper-responsiveness in hypoxic pulmonary hypertension requires serine 324

Background and Purpose

Dysregulation of the thromboxane A₂ (TP) receptor, resulting in agonist hypersensitivity and hyper-responsiveness, contributes to exaggerated vasoconstriction in the hypoxic pulmonary artery in neonatal persistent pulmonary hypertension. We previously reported that hypoxia inhibits TP receptor phosphorylation, causing desensitization. Hence, we examined the role of PKA-accessible serine residues in determining TP receptor affinity, using site-directed mutational analysis.

Experimental Approach

Vasoconstriction to a thromboxane mimetic and phosphorylation of TP receptor serine was examined in pulmonary arteries from neonatal swine with persistent pulmonary hypertension and controls. Effects of hypoxia were determined in porcine and human TP receptors. Human TPα serines at positions 324, 329 and 331 (C-terminal tail) were mutated to alanine and transiently expressed in HEK293T cells. Saturation binding and displacement kinetics of a TP antagonist and agonist were determined in porcine TP, wild-type human TPα and all TP mutants. Agonist-elicited calcium mobilization was determined for each TP mutant, in the presence of a PKA activator or inhibitor, and in hypoxic and normoxic conditions.

Key Results

The Ser324A mutant was insensitive to PKA activation and hypoxia, had a high affinity for agonist and increased agonist-induced calcium mobilization. Ser329A was no different from wild-type TP receptors. Ser331A was insensitive to hypoxia and PKA with a decreased agonist-mediated response.

Conclusions and Implications

In hypoxic pulmonary hypertension, loss of site-specific phosphorylation of the TP receptor causes agonist hyper-responsiveness. Ser324 is the primary residue phosphorylated by PKA, which regulates TP receptor-agonist interactions. Ser331 mutation confers loss of TP receptor-agonist interaction, regardless of PKA activity.     

The effects of the phytoestrogen genistein on the postnatal development of the rat.

The present studies report the effects on neonatal rats of oral exposure to genistein during the period from birth to postnatal day (PND) 21 to generate data for use in assessing human risk following oral ingestion of genistein. Failure to demonstrate significant exposure of the newborn pups via the mothers milk led us to subcutaneously inject genistein into the pups over the period PND 1-7, followed by daily gavage dosing to PND 21. The targeted doses throughout were 4 mg/kg/day genistein (equivalent to the average exposure of infants to total isoflavones in soy milk) and a dose 10 times higher than this (40 mg/kg genistein). The dose used during the injection phase of the experiment was based on plasma determinations of genistein and its major metabolites. Diethylstilbestrol (DES) at 10 micro g/kg was used as a positive control agent for assessment of changes in the sexually dimorphic nucleus of the preoptic area (SDN-POA). Administration of 40 mg/kg genistein increased uterus weights at day 22, advanced the mean day of vaginal opening, and induced permanent estrus in the developing female pups. Progesterone concentrations were also decreased in the mature females. There were no effects in females dosed with 4 mg/kg genistein, the predicted exposure level for infants drinking soy-based infant formulas. There were no consistent effects on male offspring at either dose level of genistein. Although genistein is estrogenic at 40 mg/kg/day, as illustrated by the effects described above, this dose does not have the same repercussions as DES in terms of the organizational effects on the SDN-POA.     

Withania somnifera shows a protective effect in monocrotaline-induced pulmonary hypertension

Abstract

Context: Withania somnifera (Linn.) Dunal (Solanaceae), a clinically used herbal drug in Ayurveda, shows potent antioxidant, anti-inflammatory, pro-apoptotic, and cardioprotective effects. However, the efficacy of W. somnifera in pulmonary hypertension (PH), a cardiopulmonary disorder, remains unexplored.

Objective: The present study investigates the effect of W. somnifera root powder on monocrotaline (MCT)-induced PH in rats.

Materials and methods: In preventive studies, W. somnifera root powder (50 and 100?mg/kg/d, p.o.) was administered from day 1 following single administration of MCT (60?mg/kg, s.c.) in Sprague–Dawley (SD) rats. After 35?d, right ventricular pressure (RVP) was measured in anesthetized rats. Various physical markers of right ventricular hypertrophy (RVH) were measured in isolated hearts. Markers of endothelial function, inflammation, and oxidative stress were estimated in lung homogenate. Vasoreactivity of pulmonary arteries was also studied. In therapeutic treatment, W. somnifera (50 and 100?mg/kg/d, p.o.) was administered from day 21 to 35 post-MCT administration.

Results: Preventive treatment with 50 and 100?mg/kg W. somnifera significantly reduced the RVP (32.18?±?1.273?mm?Hg and 29.98?±?1.119?mm?Hg, respectively, versus 42.96?±?1.789?mm?Hg of MCT) and all markers of RVH in MCT-challenged rats. There was an improvement in inflammation, oxidative stress and endothelial dysfunction, and attenuation of proliferative marker and apoptotic resistance in lungs. Therapeutic treatment with W. somnifera (100?mg/kg) also reduced RVP and RVH.

Discussion: This study demonstrated that W. somnifera significantly protected against MCT-induced PH due to its antioxidant, anti-inflammatory, pro-apoptotic, and cardioprotective properties.     

腺苷对慢性低氧高二氧化碳大鼠肺动脉高压的影响

目的　观察腺苷对慢性低氧高二氧化碳大鼠血流动力学的影响及氨茶碱的拮抗作用。方法　从大鼠肺动脉内注入腺苷溶液。氨茶碱组大鼠预先注入氨茶碱进行处理。结果　 2 5 μg·kg-1·min-1组 (T组 ) ,5 0 μg·kg-1·min-1组 (F组) ,10 0 μg·kg-1·min-1组 (H组 )用药后平均肺动脉压(mPAP)分别降低 18 5 %± 9 9% ,2 7 1%± 4 5 % ,37 2 %± 7 2 % ,明显低于用药前 (P均 <0 0 1) ,而NO水平则明显升高 (P <0 0 5 ,P <0 0 1,P <0 0 1)。T组 ,F组用药后mPAP/mSAP(平均体循环压 )明显低于用药前 (P <0 0 1,P<0 0 5 ) ,H组差异无显著性 (P >0 0 5 )。氨茶碱组用药后mPAP与F组比较差异有显著性 (P <0 0 1)。结论　腺苷剂量依赖性降低慢性低氧高二氧化碳大鼠的肺动脉高压 ,其机制可能部分依赖于内皮细胞NO的释放。小剂量腺苷对肺循环具有良好选择性。氨茶碱能拮抗腺苷舒张肺血管的作用。     

阿托伐他汀对慢性阻塞性肺疾病合并肺动脉高压患者血清炎症因子水平、肺功能及右心室重塑的影响

目的 探讨阿伐他汀对慢性阻塞性肺疾病（COPD）合并肺动脉高压患者血清炎症因子水平、肺功能和右心室重塑的影响。方法 将宝鸡市中心医院自2013年12月-2016年12月收治的COPD合并肺动脉高压患者106例作为研究对象,随机分为研究组和对照组,各53例,对照组患者给予常规基础治疗,研究组患者在对照组治疗的基础上加用阿伐他汀进行治疗,连续治疗3个月。检测患者肺功能、右心室重塑功能及炎症因子相关指标,评价两组患者的临床疗效。结果 研究组患者临床总有效率为94.34%,对照组为79.25%,组间比较差异显著（P<0.05）。治疗前两组患者第一秒用力呼气容积（FEV₁）、用力肺活量（FVC）水平比较差异不显著,治疗后研究组患者FVC和FEV₁水平显著高于对照组（P<0.05）。与治疗前比较,两组治疗后舒张末期左心室内径（LVID）、舒张末期左心室后壁厚度（LVPW）、三尖瓣最大反流速度（TRV_max）、右室射血分数（RVEF）均升高,舒张末期右心室内径（RVAD）降低,差异显著（P<0.05）;治疗后研究组指标LVID、LVPW、TRV_max、RVEF高于对照组,RVAD低于对照组,差异显著（P<0.05）。治疗前两组患者C反应蛋白（CRP）、内皮素（ET）和白细胞介素（IL-6）水平比较差异不显著,治疗后研究组患者CRP、ET、IL-6水平降低程度显著优于对照组（P<0.05）。结论 阿伐他汀有效改善COPD联合肺动脉高压患者血清炎症因子水平、肺功能及右心室重塑的影响,临床效果显著,可推广使用。