高镁饮食对大鼠缺氧性肺血管收缩反应和慢性缺氧性肺动脉高压的影响

本课题观察了高镁饮食对大鼠缺氧性肺血管收缩反应(HPV)和慢性缺氧性肺动脉高压的影响。大鼠进高镁饲料(每公斤普通饲料加镁1000mg)10周后,血浆镁浓度为2.58mEq/L,显著高于对照组大鼠的血浆镁浓度。慢性常压缺氧(吸入气含10%O_2,每天8小时,连续14天)后,与缺氧对照大鼠相比,进高镁饲料盼大鼠的平均肺动脉压(Ppa)和肺血管阻力(PVR)较低,肺血管对缺氧的反应性(△PVR%)较低,同时右心室肥大也较轻。血粘度和红细胞比积在慢性常压缺氧后均增高,但进高镁饲料大鼠的血粘度和红细胞比积与缺氧对照组大鼠无差别。结果表明,镁可以降低PVR和HPV,从而缓解由慢性缺氧引起的肺动脉高压和右心室肥大。     

慢性肺动脉高压大鼠肺小动脉内HIF-1α的表达增强并与NO有关

慢性低氧引起肺血管收缩、肺血管重建而致肺血管阻力持续升高,最终可导致肺动脉高压和右心室肥大,其发病机制至今尚不十分清楚。低氧诱导因子-1α(H IF-1α)作为一种转录因子,是一种重要的肺动脉对低氧反应的中介物。本实验采用慢性低氧伴高二氧化碳性肺动脉高压大鼠模型,观察H     

不同种系慢性缺氧大鼠肺血管反应性的研究

本文用白三烯(leukotrienes,LT)合成抑制剂乙胺嗪和前列腺素(prostaglandins,PG)合成抑制剂消炎痛,分别或同时阻断LT,PG的生成,以探讨LT和PG在不同种大鼠慢性缺氧性肺血管反应中的作用。结果显示:乙胺嗪可以阻断Wistar大鼠慢性缺氧性肺动脉高压形成,(?)pa由慢性缺氧时3.2±0.04kPa降到2.4±0.05kPa,PVR从76271±3274dyn·s·cm~(-5)下降为35948±3182dyn·s·cm~(-5)(P<0.05)。右心室肥厚也明显地减轻,RV/LV S慢性缺氧时0.36±0.01,用药后减少到0.26±0.01(P<0.05)。消炎痛在Wistar大鼠缺氧性肺动脉高压形成中有增强作用,使慢性缺氧时的(?)pa 3.2±0.04kPa上升到3.7±0.07kPa,PVR由76271±3274dyn·s·cm~(-5)增加到93780±4264dyn·s·cm~(-5)(P<0.05)。Hilltop大鼠对缺氧更敏感,慢性缺氧性肺动脉高压和右心室肥厚均较Wistar大鼠明显。(?)pa分别为4.0±0.17kPa对3.2±0.04kPa,RV/LV S分别为0.39±0.23对0.36±0.01(P<0.05)。乙胺嗪并不能完全阻止Hilltop大鼠缺氧性肺动脉高压形成,用药后(?)pa为3.3±0.12kPa,明显低于慢性缺氧时4.0±0.17kPa,但仍显著高于常压对照组的2.3±0.03kPa。消炎痛对其缺氧性肺动脉高压和右心室肥厚无明显影响。结果提示:两种大鼠对缺氧反应性的差异可能同LT的介导作用和扩管性PG的调节作用的差别有关。     

慢性低氧对大鼠血浆尾加压素Ⅱ浓度和右心室尾加压素Ⅱ受体的影响

目的: 探讨尾加压素Ⅱ(UII)受体在慢性低氧性右心室肥大中的作用。方法: 在慢性低氧高二氧化碳肺动脉高压、右心室肥大的大鼠模型上, 采用放射性配基结合法, 测定不同缺氧时间(2周、4周)右心室肌浆膜上UII受体的结合率, 放免法测定血浆UII的含量。结果: 慢性低氧高二氧化碳大鼠的肺动脉平均压(mPAP)和右心室(RV)与左心室加室间隔(LV+S)重量比(RV/LV+S)明显高于对照组(P<0.01); UII受体结合位点(B_max), 低氧2周组比正常对照组高26.7%(P<0.01), 4周组又比2周组高19.8%(P<0.01), UII受体亲和力(Kd值)3组间无显著差别(P>0.05); 血浆UII水平呈先高后降的双向变化, 2周组比正常组高33.5%(P<0.01), 而4周组比2周组低15.4%(P<0.05), 与正常对照组相近。结论: 慢性低氧高二氧化碳使大鼠右心室肌浆膜上UII受体增加, 其变化可能参与了右室肥大。     

黄芪对大鼠缺氧性肺动脉高压功能形态学的影响

为观察黄芪对缺氧性大鼠腺泡内肺动脉构形重组和肺动脉高压是否具有阻抑效应，以期为该药在肺动脉高压的防治方面提供实验依据。在常压低氧条件下，选用６０只大鼠，分低氧组、低氧加黄芪组和正常组，在实验第１５天、３０天分别测量右心室收缩压，计算右心室肥大指数、光镜与电镜观察肺血管病变及进行显微形态计量学检测，动态观察了黄芪对低氧大鼠腺泡内肺动脉构形重组及肺动脉高压的影响。结果显示黄芪不仅能拮抗缺氧性腺泡内肺动脉收缩，减轻低氧对肺动脉壁细胞的损伤，还能阻抑腺泡内肺动脉中膜肌化增强和外膜纤维母细胞增生。说明黄芪有明显阻抑低氧性腺泡内肺动脉构形重组和预防缺氧性肺动脉压升高的作用。     

慢性低氧高二氧化碳性肺动脉高压大鼠肺小血管尾加压素Ⅱ表达的动态变化

目的动态观察内源性尾加压素Ⅱ(urotensinⅡ,UⅡ)在慢性低氧高二氧化碳性肺动脉高压大鼠不同节段肺细小动脉的表达,以探讨其在肺动脉高压发生发展中的作用。方法对不同低氧时间(1、2、4周)的大鼠模型:(1)测定平均肺动脉压力(mPAP),右心室游离壁(RV)和左心室加室间隔(LV+S)的重量比。(2)免疫组化方法检测不同节段肺细小动脉UⅡ蛋白的表达。(3)光镜下观察三级肺细小动脉显微结构的变化,用图像分析仪心肺血管分析软件测定肺细小动脉管壁面积/管总面积(WA/TA)和肺细小动脉中膜厚度(PAMT)。结果(1)mPAP、RV/LV+S的比较:低氧高二氧化碳各组均高于正常对照组(P<0.01);2周组比1周组分别高22.5%与14.1%(P均<0.01);4周组与2周组无显著差别(P>0.05)。(2)免疫组化显示三级肺细小动脉(近端至远端)UⅡ蛋白表达的平均吸光度值1周组较正常对照组分别高40.4%、38.9%、22.9%(P均<0.01);2周组较1周组分别高15.2%、14.7%、16.6%(P均<0.01);而4周组与1周组间无显著差别。(3)肺小动脉显微结构的变化:4HH组各级血管均有显著重构,1HH组无明显变化,2HH组介于两者之间。结论慢性低氧高二氧化碳性大鼠肺动脉高压形成过程中,肺内各级细小动脉的UⅡ的表达均呈现明显的上调,并与肺动脉压升高、右心室肥大的程度基本一致,提示UⅡ在慢性低氧高二氧化碳性肺动脉高压的形成机制中具有重要的病理生理意义。     

慢性低氧性肺动脉高压大鼠肾上腺髓质素前体N端20肽的变化

目的：探讨慢性低氧性肺动脉高压和肺血管结构重建时肾上腺髓质素前体N端20肽（PAMP）的变化。方法:将18只雄性Wistar大鼠随机分为对照组和低氧组，每组各9只。常压低氧2周后，以右心导管法测定肺动脉平均压（mPAP），检测右心室与左心室加室间隔比值 ［RV/(LV+S)］，观测肺血管显微和超微结构的变化。并且以放免法测定血浆中PAMP含量，以免疫组化法检测肺组织中PAMP表达，以原位杂交检测肺组织中肾上腺髓质素（ADM） mRNA的表达。结果: 低氧组大鼠mPAP及RV/（LV+S）均明显高于对照组（均P<0.01）。光镜下，肺小血管肌化程度明显增强，肺中、小型肌型动脉相对中膜厚度明显增加。电镜下，肺腺泡内动脉内皮细胞增生、肿胀，内弹力层粗细不均，平滑肌细胞肥厚、向合成表型转化。并且低氧组大鼠血浆PAMP含量明显高于对照组（P<0.01），肺动脉PAMP表达和ADM mRNA表达均明显增强。结论：低氧后肺动脉PAMP表达和血浆PAMP含量的上调可能参与了慢性低氧性肺动脉高压和肺血管结构重建的形成。     

肾上腺髓质素缓解大鼠低氧性肺动脉高压

目的探讨肾上腺髓质素(ADM)对大鼠低氧性肺动脉高压的防治作用及机制。方法雄性Wistar大鼠18只,分为对照组、低氧组和低氧 ADM组,每组6只。持续皮下注射ADM1-50后,测定平均肺动脉压(mPAP)、右心室肥大指数RV/(LV S)、肺小动脉病理及形态计量学和体循环平均压(mSBP),放免法测定肺动脉血浆ADM水平,原位杂交测定肺动脉ADMR mRNA的表达。结果①低氧组大鼠mPAP,RV/(LV S),管壁厚度与血管外径比值(MT%)及管壁面积与血管面积比值(MA%)均显著升高(P<0.01);ADM组显著缓解以上变化(P<0.01)。②低氧组与低氧 ADM组肺动脉血浆ADM浓度均高于对照组,且低氧 ADM组较低氧组ADM浓度低(P<0.05)。③低氧组与低氧 ADM组的ADMR mRNA表达较对照组增强(P<0.01)。结论持续皮下注射ADM对慢性低氧所致的肺动脉高压及肺血管重塑有预防和部分逆转作用。     

吸烟引起肺血管反应性变化的影响因素—动物种属与吸烟时间

本文研究吸烟引起的缺氧性肺血管收缩反应(HPV)的变化与动物种属及吸烟时间的关系,以及肺血管反应性变化的机制。以肺血管阻力变化百分率(△PVR%)或肺阻抗血流图收缩波波幅变化率(△H%)作为缺氧性肺血管收缩反应强度的指标。实验结果发现,急性吸烟使大鼠的HPV增强(△PVR%从55.0±15.6%增至102.3±12.4%),主要由白三烯介导;使幼猪的HPV减弱(△PVR%从65.2±12.5%减至55.9±9.8%),主要由肾上腺素β受体介导;使人的HPV增强(△H%从20.6±2.6%增至31.1±4.1%),前列腺素和白三烯起介导作用。大鼠吸烟一个月后HPV反而下降(△PVR%为11.4±6%,同期对照组为31.1±0.8%),与扩管性前列腺素增多和白三烯生成减少有关。     

慢性低氧对大鼠肺血管L-精氨酸

目的:探讨慢性低氧对大鼠肺血管L-精氨酸/一氧化氮(L-Arg/NO)途径的影响。方法:采用慢性低氧性肺动脉高压(HPH)大鼠肺血管孵育,测定慢性HPH对大鼠肺动脉L-Arg转运,一氧化氮合酶(NOS)活性和NO生成释放的影响。结果:(1)低氧4周大鼠肺动脉平均压(mPAP)比对照组高33.7%(P＜0.01),右心室(RV)和左室加室间隔(LV+S)重量比值(RV/LV+S)高44.2%(P＜0.01)。(2)低氧对血浆L-Arg含量无明显影响。(3)低氧大鼠离体孵育的肺动脉摄取低浓度(0.2mmol/L)和高浓度(5.0mmol/L)[³H]-L-Arg分别低于对照组15.8%(P＜0.05)和27.2%(P＜0.01)。(4)低氧大鼠肺动脉tNOS、iNOS和cNOS活性较对照组高38.0%、32.8%和53.0%(P＜0.01)。(5)低氧大鼠血浆NO含量低于对照组,与mPAP和RV/LV+S呈负相关(P＜0.01)。结论:慢性HPH时NOS活性代偿性增强,但L-Arg转运受损使血浆NO生成仍减少,说明L-Arg转运是NO生成的重要限速步骤。     

P63 in pulmonary epithelium,pulmonary squamous neoplasms,and other pulmonary tumors

p63 is a p53-homologous nuclear protein that appears to play a crucial role in regulation of stem cell commitment in squamous and other epithelia. In this study, p63 expression was examined in benign lung and in neoplasms of pulmonary origin. Eighty sections from routinely fixed and processed archival bronchoscopic biopsy or lobectomy specimens were pretreated with citric acid (pH 6.0) for antigen retrieval, then incubated overnight with anti-p63 monoclonal antibody 4A4. Slides were stained using a streptavidin-biotin kit and diaminobenzidine as chromagen, and were counterstained with hematoxylin. In normal lung, p63 intensely stained nuclei of bronchial reserve cells but did not stain ciliated cells, alveolar epithelial cells, or nonepithelial cells. The lower strata of squamous metaplastic bronchial epithelium stained positively. All squamous-cell carcinomas stained positively (n = 30). In some well-differentiated carcinomas, staining was found at the periphery of tumor nests but was negative in central zones showing squamous maturation. Poorly differentiated carcinomas showed very high proportions (80% to 100%) of p63-positive nuclei. All small-cell carcinomas were p63 negative (n = 9). Staining of bronchioloalveolar carcinomas (n = 7) and adenocarcinomas (n = 23) was variable: some tumors showed no detectable staining, others showed heterogeneously positive staining. Adenosquamous carcinomas (n = 5) displayed a unique basalar staining pattern. Carcinoid tumors were almost entirely negative (n = 5). We conclude that p63 is expressed in benign bronchial stem cells, in neoplastic cells with either squamous differentiation or squamous differentiating potential, and in a subpopulation of adenocarcinomas. p63 immunostaining may also aid in some histopathologic distinctions, such as in small biopsies where the differential diagnosis is poorly differentiated squamous carcinoma versus small-cell carcinoma. A stem cell biology-based classification system for squamous carcinomas is proposed.     

肺部超声对重症肺部感染患者肺通气的评估价值

目的:探讨肺部超声评价重症肺部感染患者通气情况的应用价值。方法:选取88例重症肺部感染患者,采用半定量方法对肺部超声征象进行评分,以CT检查结果为金标准,分析肺部超声评分与患者肺通气的关系;同时分析存活和死亡患者临床资料、肺部超声评分的差异,以及肺部超声评分预测患者死亡的价值。结果:88例患者全肺超声评分平均为（18.50±2.12）分,全肺CT值平均为（-620.50±88.13） HU,不通气/低通气肺组织比例平均为（10.41±3.35）%,正常通气肺组织比例平均为（71.54±6.69）%,过度通气肺组织比例平均为（17.65±4.11）%;患者肺部超声评分与全肺CT值、不通气/低通气肺组织比例呈正相关（r=0.775、0.648, P<0.05）,与正常通气肺组织比例、过度通气肺组织比例无明显相关性（r=-0.170、0.046, P>0.05）;死亡组患者年龄、糖尿病比例、APACHEⅡ评分、肺泡-动脉氧分压差、机械通气治疗和肺部超声评分分别为（59.28±8.12）岁、44.83%、（22.19±2.40）分、（344.40±82.29） mmHg、72.41%和（20.20±1.72）分,明显高于存活组（P<0.05）,而氧合指数为（104.42±21.18）,明显低于存活组（P<0.05）;Logistic回归分析结果显示:年龄、APACHEⅡ、肺部超声评分是重症肺部感染患者死亡的影响因素（OR=1.758、2.841、2.440, P<0.05）;肺部超声评分预测重症肺部感染患者死亡的ROC曲线下面积为0.901（95%CI:0.836~0.966）,截断值为20分,灵敏性和特异性分别为82.80%和84.70%。结论:肺部超声可以作为重症肺部感染患者肺通气的评估指标,同时其在预测患者预后方面有一定应用价值。     

The pulmonary matrix, glycosaminoglycans and pulmonary emphysema

This paper reviews recent evidence of the effect of intratracheal hyaluronan (HA) to limit the induction of experimental emphysema in hamsters. Experimental emphysema was induced by both neutrophil and pancreatic elastase instilled intratracheally. Emphysema was quantified anatomically by measurement of alveolar mean linear intercept. Hyaluronidase, instilled intratracheally, enhanced the induction of experimental emphysema. Air-space size measured one week after intratracheal instillation of elastase showed that administration of 1 mg HA immediately following elastase administration resulted in a marked reduction in air-space enlargement (82 microM vs 122 microM, p < 0.01). Similarly, animals given either 1 or 2 mg HA 2 h before elastase or 2mg HA 1 h after elastase showed a significant decrease in air-space enlargement compared to controls (96 microM, 88 microM vs 120 microM and 66 microM vs 104 microM, respectively; p < 0.05. Experimental emphysema induced by neutrophil elastase was also limited by the administration of 1 or 4 mg of HA, administered 2 h prior to elastase (57 and 59 microM, respectively vs 64 for controls, p < 0.05). Characterization of administered HA showed a mean molecular weight of 104,800 Da, less than 5% protein and a uronic acid/hexosamine ratio of 1, which is characteristic of HA. Studies using fluorescein-labeled hyaluronan (HA) showed fluorescence associated with interstitial, pleural and vascular elastic fibers. The mechanism of attachment of the administered HA to elastin remains unknown. Fluorescein labeling of elastin was visible for at least 4 h post-instillation. These studies indicate a protective effect of hyaluronan against elastase degradation of pulmonary elastin in vivo by both pancreatic and neutrophil elastases. The anatomical studies further suggest a mechanism of protective coating of hyaluronan which may limit access to pulmonary elastin from neutrophils and alveolar macrophages. Results also suggest that a reduction in pulmonary hyaluronan content increases the susceptibility of elastin to degradation by elastases. These studies provide evidence for an antielastase effect of hyaluronan which is not dependent upon enzyme inhibition but on anatomical protection of pulmonary elastin by other mechanisms.     

Changes in pulmonary hemodynamics in acute pulmonary edema

Summary Experiments were made on dogs to study the hemodynamic changes following intravenous injections of chloramine and adrenaline. Chloramine injections were followed by the development of a severe pulmonary edema in an of the dogs. In most of them, however, the capillary pressure in the pulmonary circulation increased, but insignificantly. The great increase in the pulmonary capillary pressure following adrenaline injection did not culminate in the development of edema or caused very slight edema. The conclusion is drawn that increase of filtration pressure is not an indispensable decisive factor for the development of pulmonary edema, even if it is concurrent with considerable disturbances in the pulmonary circulation.(Presented by Academician V. V. Parin) Translated from Byulleten' Éksperimental'noi Biologii i Meditsiny, Vol. 60, No. 8, pp. 25–29, August, 1965     

T-cell signature cytokines distinguish pulmonary sarcoidosis from pulmonary tuberculosis

Sarcoidosis is a systemic inflammatory disorder characterized by tissue infiltration due to mononuclear phagocytes and lymphocytes and associated noncaseating granuloma formation. Pulmonary sarcoidosis (PS) shares a number of clinical, radiological, and histopathological characteristics with that of pulmonary tuberculosis (PTB). Due to this, clinicians face issues in differentiating between PS and PTB in a substantial number of cases. There is a lack of any specific biomarker that can diagnose PS distinctively from PTB. We compared T-cell-based signature cytokines in patients with PS and PTB. In this study, we proposed a serum biomarker panel consisting of cytokines from cells: T helper (Th) 1 [interferon-gamma (IFN-γ); tumor necrosis factor-alpha (TNF-α)], Th9 [interleukin (IL)-9], Th17 [IL-17], and T regulatory (Treg) [IL-10; transforming growth factor-beta (TGF-β)]. We performed the principal component analysis that demonstrated that our serum cytokine panel has a significant predictive ability to differentiate PS from PTB. Our results could aid clinicians to improve the diagnostic workflow for patients with PS in TB endemic settings where the diagnosis between PS and PTB is often ambiguous.     

Mycobacterial pulmonary infections in patients with idiopathic pulmonary fibrosis

Patients with idiopathic pulmonary fibrosis (IPF) have an increased risk for developing tuberculosis (TB). However, no studies have been reported regarding the development of nontuberculous mycobacterium (NTM) lung disease (NTMLD). We reviewed 795 patients with IPF from five university hospitals who were diagnosed by histological or radio-clinical criteria. In the 795 patients with IPF, pulmonary infections with mycobacterium tuberculosis (MTB) and NTM were found in 35 (4.4%) and 16 patients (2.0%), respectively, which was a higher frequency than that found in the general population. TB was more common in patients treated with immunosuppressants than in those who did not receive immunosuppressants (2.6% vs 1.4%, P = 0.12). Among the IPF patients who had mycobacterial infections,immunosuppressant users developed TB or NTMLD within 1 yr after treatment with immunosuppressants,while those occurred later than 2 yr after diagnosis of IPF in the subjects that did not receive immunosuppressants. Among 51 IPF patients who had mycobacterial infections, 9 (18%) died during follow-up. Of these, three died due to progression of pulmonary tuberculosis. TB and NTMLD is relatively common in patients with IPF in Korea and may be fatal in some groups. Careful evaluation of TB and NTMLD is necessary not only for immunosuppressant users, but also for nonusers with IPF.     

A case of pulmonary capillary hemangiomatosis with pulmonary fibrosis associated with MMP-9 related pulmonary remodeling

Pulmonary capillary hemangiomatosis (PCH) is a rare cause of pulmonary hypertension. It is characterized capillary proliferation within the alveolar septa. Here, we report a case of PCH with extensive pulmonary fibrosis. A 52-year-old man with a clinical diagnosis of non-specific interstitial pneumonia died of respiratory failure with severe pulmonary hypertension. Autopsy revealed pronounced right ventricle hypertrophy and pulmonary fibrosis. Consistent with clinical diagnosis, histological examination revealed diffuse pulmonary fibrosis, in addition, it also disclosed marked capillary proliferation within the alveolar septa as well as the fibrotic pulmonary stroma, suggesting the presence of PCH. Hemosiderin-laden macrophages had accumulated in the capillary proliferative area, and bronchiolar-type metaplasia was conspicuous in the fibrotic lesion. Proliferated capillaries were surrounded by fine collagen and α-smooth muscle actin-positive myofibroblasts. Immunohistochemistry revealed that type IV collagen around capillaries in the area of the PCH without inflammation disappeared in the area with inflammation. In addition, the PCH lesion contained significant numbers of macrophages expressing matrix metalloproteinase (MMP) 9 and type II pneumocytes positive for vascular endothelial growth factor. Although pulmonary fibrosis is a distinctive disease entity, different from PCH, MMP-9-driven destruction of the basement membrane may promote unusual pulmonary remodeling, which, in this case, resulted in extensive pulmonary fibrosis.