雌激素对H_2O_2诱导的氧化应激的保护作用及机制

为了探讨雌激素17β-estradiol对H2O2诱导的氧化应激的影响及其可能机制。本研究将H2O2作用于大鼠皮层神经元,利用四甲基偶氮唑盐(MTT)检测单独H2O2或者17β-estradiol存在时其对细胞活力和乳酸脱氢酶(LDH)释放的影响;检测单独H2O2或者17β-estradiol存在时其对糖原合成激酶-3β(GSK-3β)活性的影响及其对磷酸化和非磷酸化GSK-3β表达的影响;检测GSK-3β抑制剂LiCl对H2O2诱导的细胞活力的影响;检测雌激素受体抑制剂ICI-182780存在时17β-estradiol对GSK-3β表达的影响。结果显示:(1)H2O2作用于大鼠皮层神经元后显著降低细胞的活力,各种浓度的17β-estradiol预处理细胞后均能部分阻断H2O2对细胞活力的影响;(2)H2O2作用后显著增加细胞乳酸脱氢酶的释放,而17β-estradiol则部分拮抗此种作用;(3)H2O2增加了GSK-3β的活性,而提前加入17β-estradiol则可以降低H2O2诱导的GSK-3β活性增加;(4)H2O2降低了GSK-3β的磷酸化,而17β-estradiol则部分拮抗了这种作用;(5)GSK-3β抑制剂LiCl也可以拮抗H2O2诱导的细胞活力下降;(6)与对照组相比,17β-estradiol本身亦可增加GSK-3β的磷酸化,此作用可被雌激素受体抑制剂ICI-182780部分拮抗,而ICI-182780本身对GSK-3β的磷酸化无显著影响。以上结果提示,17β-estradiol可以拮抗H2O2诱导的氧化应激作用,17β-estradiol通过与其受体结合而抑制GSK-3β的活性可能是其发挥保护作用的机制之一。     

白三烯受体拮抗剂治疗支气管哮喘的疗效评价

用白三烯受体拮抗剂-扎鲁司特对轻、中度支气管哮喘患者进行了观察.40例患者随机分为2组,治疗组24例,口服扎鲁司特20mg,每天2次,并按需使用β-2受体激动剂;对照组16例,按需使用β-2受体激动剂,疗程均为4周,治疗前后观察患者的夜间憋醒次数、β-2受体激动剂使用次数、呼气峰流速(PEF).结果扎鲁司特治疗组治疗前后患者的夜间敝醒次数、β-2受体激动剂使用次数均显著减少,PEF明显改善;对照组治疗前后上述指标无明显改变;治疗后,治疗组较对照组夜间憋醒次数、β-2受体激动剂使用次数均显著减少,PEF明显改善.结论白三烯受体拮抗剂对轻、中度哮喘患者具有减轻症状、改善肺功能、抗炎作用.     

成骨细胞与纳米植入材料相互作用研究进展

骨植入材料与周围骨组织的骨整合对于材料的稳定性有着巨大影响,其中成骨细胞产生各种不同的蛋白质分子完成胞体与材料以及周围细胞的连接.这些蛋白质分子包括细胞外基质蛋白、细胞骨架蛋白和黏附蛋白等.实验证实:带有纳米表面结构的植入材料具有良好的生物相容性和理化特性;纳米表面粗糙程度大大增加,亲水性、电化学特性明显提高,更有利于细胞外基质蛋白等的黏附和相互作用,从而促进成骨细胞黏附、增殖和分化;纳米表面也能促进成骨细胞产生前列腺素E2(prostagIandin E2,PGE2)、转化生长因子β(transforming growth factor-β,TGF-β)等细胞因子,影响新骨形成.纳米表面骨植人材料及其对成骨细胞的影响的作用机制还有待进一步研究.     

冠心病95例血β_2微球蛋白放射免疫测定

<正> 1968年Berqqara等首先从肾小管病变患者尿中分离出β_2微球蛋白(β-microglobulin,β_2m)。近年来β_2m的临床应用引起了人们广泛重视,已逐渐被认为是肾脏、肝脏、结缔组织等疾病及恶性肿瘤的一种较灵敏的诊断方法,对估计某些疾病的预后也是一项有效的指标。心脏病人血β_2m有何变化目前研究尚少,现将我们测定的95例冠心病人血β_2m的结果报告如下。     

丹参素对肝星状细胞TGF-β信号转导的影响

目的： 观察丹参素对转化生长因子β1（TGF-β1）诱导活化的大鼠肝星状细胞(HSCs)Smad信号转导通路的影响。方法：体外分离、培养大鼠肝HSCs,用不同浓度丹参素作用于HSCs,检测丹参素对HSCs增殖和TGF-β1刺激后HSCs增殖的影响;观察丹参素对TGF-β1刺激HSCs表达α-SMA的影响;观察HSCs转化生长因子受体(TβRⅠ、Ⅱ)的表达;观察丹参素和TGF-β1作用HSCs后,其Smad2、Smad3、Smad7 mRNA表达的变化。结果：(1)丹参素在0.0625 mmol/L-1 mmol/L时,对HSCs的生长增殖具有抑制作用 (P<0.05);丹参素对TGF-β1诱导的HSCs增殖也具有明显的抑制作用 (P<0.05)。(2)丹参素0.25 mmol/ L作用HSCs能下调α-SMA的表达(P<0.05),也能下调TGF-β1诱导的HSCs的α-SMA表达(P<0.05)。（3）HSCs中TβRⅠ、Ⅱ的表达定位于细胞膜上,丹参素能下调活化HSCs中TβRⅠ、Ⅱ的表达（P<0.05或P<0.01）。 (4) TGF-β1促进HSCs中Smad2、Smad3、Smad7 mRNA的表达（P<0.01）;丹参素能下调TGF-β1诱导的HSCs内Smad2、Smad3 mRNA的表达(P<0.05),并能上调Smad7 mRNA表达(P<0.05)。 结论：体外细胞实验表明,丹参素能通过下调活化HSCs细胞膜上TβRⅠ、Ⅱ蛋白的表达来抑制HSCs的活化增殖。丹参素能上调HSCs内Smad7 mRNA表达,并下调Smad2、Smad3 mRNA表达,抑制HSCs活化,并抑制TGF-β1诱导的HSCs活化。     

小剂量罗红霉素对小气道疾病患者血清中三种细胞因子的影响

小气道疾病(SAD)是慢性阻塞性肺疾病(COPD)的早期病理过程,有多种细胞因子参与,目前无确切的干预方法,本课题研究SAD细胞因子的变化及小剂量罗红霉素对SAD各种细胞因子的影响。首先研究健康查体确诊的SAD患者及非SAD患者的细胞因子的变化;其次对161例支原体抗体阴性的SAD患者,随机分为罗红霉素治疗组81例、对照组80例进行研究。治疗组口服小剂量罗红霉素0.15/d,3个月,对照组未予任何治疗,治疗开始前、治疗后1、3、6、12个月测定细胞因子TNF-α、TGF-β1、IL-8的变化,同时检查肺功能。结果SAD组患者TNF-α、TGF-β1、IL-8明显高于非SAD组,两组差异显著(P<0.05);治疗组SAD随着时间的延长TNF-α、TGF-β1、IL-8逐渐下降,肺功能逐渐好转,相关性分析,肺功能与细胞因子的变化成明显负相关(P<0.05),1年后统计治疗组SAD治愈率50%,对照组10%,两者差异显著,治疗组SAD发生率低因此,小剂量罗红霉素可有效抑制SAD细胞因子TNF-α、TGF-β1、IL-8的生成,抑制气道的慢性非特异性炎症,减少SADCOPD的发生。     

肺功能检测与舰艇潜艇远航对肺功能影响研究

肺功能检测广泛应用于呼吸系统疾病的诊断,舰艇潜艇远航人员因长期生活在高湿、高盐、高温海域,舱内空气流通受限,加之晕船、疲劳、温差变化等诸多不良因素,必然对肺功能造成影响,进而引起多种慢性呼吸道疾病。因此,本文就肺功能检测、舰艇和潜艇对肺功能的影响作一综述,旨在为进一步改善肺功能提供参考依据。     

新风胶囊通过抑制TGF-β1-ERK1信号通路保护干燥综合症模型大鼠肺功能

目的 考察新风胶囊对干燥综合征模型大鼠肺功能的作用,及其对TGF-β1-ERK1信号通路的影响.方法 将50只SD大鼠随机分为正常对照组、模型对照组和羟氯喹(HCQ)组、白芍总苷(TGP)组、新风胶囊(XFC)治疗组,每组10只,除正常对照组外,采用完全弗氏佐剂+同种鼠颌下腺抗原诱导方法,向每只大鼠两后足跖部注射与弗氏完全佐剂充分乳化后的颌下腺蛋白混合抗原0.2 mL诱发大鼠干燥综合征模型.用动物肺功能仪检测大鼠肺功能,检测各组大鼠饮水量及体质量的变化、采用免疫组化法ERK1、TGF-β1的表达,采用ELISA法检测血清细胞因子(IL-17、IL-4)的变化.结果 与正常对照组(NC)比较,模型对照组(MC)大鼠体质量、血清IL-4明显降低,饮水量、颌下腺/肺指数、颌下腺病理评分、ERK1、TGF-β1积分及IL-17升高(P＜0.01或P＜0.05),肺功能参数降低(P＜0.01或P＜0.05);与MC组比较,XFC组体质量、肺功能参数50％肺活量的最大呼气流量(FEF50)、最大呼气中段流量(MMF)升高,IL-4表达升高,饮水量、颌下腺/肺指数、颌下腺病理评分、血清IL-17的表达、ERK1、TGF-β1积分降低(P＜0.01或P＜0.05).与HCQ组相比,XFC组体质量、IL-17明显降低(P＜0.01),FEF25、FEF75、MMF升高(P＜0.01或P＜0.05);与TGP组比较,XFC组肺指数、IL-17降低(P＜0.01或P＜0.05).结论 SS大鼠存在肺功能下降,可能与TGF-β1-ERK1信号通路活化相关.中药XFC能够下调TGF-β1、抑制ERK1磷酸化、降低免疫炎症反应、改善肺功能.     

Foxp3~+ Treg、Th细胞迁移及ET-1与佐剂关节炎大鼠模型肺功能的关系

目的:观察佐剂关节炎(Adjuvant arthritis,AA)大鼠肺功能降低与辅助T细胞(Th)、调节T细胞(Treg)及Foxp3的关系。方法:将SD大鼠随机分为正常对照(NC)组和模型对照(MC)组,每组15只,向MC组大鼠右后足跖皮内注射弗氏完全佐剂0.1 ml致炎,复制成AA模型。致炎48 d后,采用小动物肺功能仪检测肺功能,酶联免疫吸附法检测内皮素(ET)-1、白细胞介素(IL)-10、γ干扰素(IFN-γ),免疫组化法检测肺组织IL-1β、IL-10表达,流式细胞仪测定Treg的表达,采用PCR与免疫印迹检测肺组织Foxp3表达。结果:与NC组相比,MC组大鼠IFN-γ、ET-1、IL-1β升高;肺功能参数50%肺活量的最大呼气流量(FEF50)、75%肺活量的最大呼气流量(FEF75)、最大呼气中期流量(MMF)、用力最大呼气流量(PEF)降低,IL-10、CD4+CD25+Foxp3+Treg、Foxp3表达降低(P<0.05或P<0.01);相关分析显示,AA大鼠肺功能参数FEF75、MMF分别与IFN-γ、Th1/Th2、IL-1β呈负相关,FEF50、PEF与ET-1呈负相关;PEF、FEF75分别与IL-10、Foxp3 mRNA、Foxp3蛋白呈正相关,FEF75与CD4+CD25+Foxp3+Treg呈正相关(P<0.05或P<0.01)。结论:AA大鼠肺功能下降可能是佐剂致炎后Th细胞分泌紊乱、细胞因子失衡、内皮细胞增多,使肺组织Foxp3表达抑制,进而CD4+CD25-T细胞转化成CD4+CD25+Treg受阻,最终导致RA肺功能降低。     

老年人肺功能、体重与血浆T,E2水平的相互关系

性激素的水平与老年人冠心病有关,这一事实已为人们 所重视。而老年人肺泡弹性及肺功能降低[1]则会加重或促 进肺气肿及肺心病的发生和发展。近年来,已经证明不仅肺 组织内一些内皮细胞有雄、雌激素的受体和抗雌激素的结合 点[2],而且肺也是性激素代谢和转化的重要器官之一[3]。反 之,性激素对肺组织的生理功能也有重要的影响[4]。肥胖者 高血压、冠心病的发生率高,并对性激素也有影响[5],亦可对 肺功能产生影响。但肥胖与肺功能的关系及和性激素之间 的相互关系,目前文献中所见甚少。本文就这一问题做一初 步探讨…     

The influences of diet and exercise on mental health through hormesis

It is likely that the capacity of the brain to remain healthy during aging depends upon its ability to adapt and nurture in response to environmental challenges. In these terms, main principles involved in hormesis can be also applied to understand relationships at a higher level of complexity such as those existing between the CNS and the environment. This review emphasizes the ability of diet, exercise, and other lifestyle adaptations to modulate brain function. Exercise and diet are discussed in relationship to their aptitude to impact systems that sustain synaptic plasticity and mental health, and are therefore important for combating the effects of aging. Mechanisms that interface energy metabolism and synaptic plasticity are discussed, as these are the frameworks for the actions of cellular stress on cognitive function. In particular, neurotrophins are emerging as main factors in the equation that may connect lifestyle factors and mental health.     

Thinking bigger: How early‐life environmental exposures shape the gut microbiome and influence the development of asthma and allergic disease

Imbalance, or dysbiosis, of the gut microbiome of infants has been linked to an increased risk of asthma and allergic diseases. Most studies to date have provided a wealth of data showing correlations between early‐life risk factors for disease and changes in the structure of the gut microbiome that disrupt normal immunoregulation. These studies have typically focused on one specific risk factor, such as mode of delivery or early‐life antibiotic use. Such “micro‐level” exposures have a considerable impact on affected individuals but not necessarily the whole population. In this review, we place these mechanisms under a larger lens that takes into account the influence of upstream “macro‐level” environmental factors such as air pollution and the built environment. While these exposures likely have a smaller impact on the microbiome at an individual level, their ubiquitous nature confers them with a large influence at the population level. We focus on features of the indoor and outdoor human‐made environment, their microbiomes and the research challenges inherent in integrating the built environment microbiomes with the early‐life gut microbiome. We argue that an exposome perspective integrating internal and external microbiomes with macro‐level environmental factors can provide a more comprehensive framework to define how environmental exposures can shape the gut microbiome and influence the development of allergic disease.     

Obesity and asthma, what are the links?

PURPOSE OF REVIEW: Obesity is a major cause of morbidity accounting for approximately 300 000 deaths each year and about 7% of the health care budget with an economic impact greater than US dollar 100 billion annually in the United States. Obesity and its sequelae such as cardiovascular disease, diabetes, arthritis or cancer have been on the rise over the last decades. The parallel time trend with an increasing prevalence of asthma has induced a lively debate about a potential link between both conditions. RECENT FINDINGS: A number of prospective studies have shown that weight gain can antedate the development of asthma. Effect modification by sex may occur as some studies have shown effects of body mass index on asthma only among females. However, sex differences are not consistent. Several hypotheses have been proposed to explain the epidemiological associations including alterations in airway mechanics and immune responses, hormonal influences and genetic factors. SUMMARY: There is evidence that obesity and overweight are associated with the development of asthma. Yet, the mechanisms underlying this relation are unclear. Weight reduction among asthmatic patients can result in improvements of lung function demonstrating the potential clinical impact of the findings.     

Asthma in children

Asthma is the most common chronic disease in childhood characterized by chronic bronchial inflammation of variable intensity accompanied by spontaneous or drug reversible airflow obstruction. The onset of asthma, clinical presentation and response to therapy are influenced by numerous genetic and environmental factors. Asthma in childhood is characterized by its heterogeneity in terms of possible etiology, degree of inflammation and airway obstruction, lung function as well as the natural course of disease that may persist and continue to adulthood. Protective factors linked to early life experiences have also been delineated which may impact the development of asthma. Pathophysiological mechanisms of allergic reaction as an excessive inflammation driven by T-helper-2 (Th2) immunity, offer poor understanding of the heterogeneity of clinical disease. A recently introduced approach defines asthma as a syndrome that comprises of several subtypes or endotypes based on entirely novel pathways to disease. Timely diagnosis and adequate treatment are necessary to prevent irreversible airway remodeling and consequent decrease in pulmonary function.     

A new approach to mechanical simulation of lung behaviour: Pressure-controlled and time-related piston movement

A mechanical lung simulator is described (an extension of a previous mechanical simulator) which simulates normal breathing and artificial ventilation in patients. The extended integration of hardware and software offers many new possibilities and advantages over the former simulator. The properties of components which simulate elastance and airway resistance of the lung are defined in software rather than by the mechanical properties of the components alone. Therefore, a more flexible simulation of non-linear behaviour and the cross-over effects of lung properties is obtained. Furthermore, the range of lung compliance is extended to simulate patients with emphysema. The dependency of airway resistance on lung recoil pressure and transmural pressure of the airways can also be simulated. The new approach enables one to incorporate time-related mechanics such as the influence of lung viscosity or cardiac oscillation. The different relations defined in the software can be changed from breath to breath. Three simulations are presented: (1) computer-controlled expiration in the artificially ventilated lung; (2) simulation of normal breathing; and (3) simulation of viscoelastance and cardiac influences during artificial ventilation. The mechanical simulator provides a reproducible and flexible environment for testing new software and equipment in the lung function laboratory and in intensive care, and can be used for instruction and training.     

Identification of SNPs in the cystic fibrosis interactome influencing pulmonary progression in cystic fibrosis

There is growing evidence that the great phenotypic variability in patients with cystic fibrosis (CF) not only depends on the genotype, but apart from a combination of environmental and stochastic factors predominantly also on modifier gene effects. It has been proposed that genes interacting with CF transmembrane conductance regulator (CFTR) and epithelial sodium channel (ENaC) are potential modifiers. Therefore, we assessed the impact of single-nucleotide polymorphisms (SNPs) of several of these interacters on CF disease outcome. SNPs that potentially alter gene function were genotyped in 95 well-characterized p.Phe508del homozygous CF patients. Linear mixed-effect model analysis was used to assess the relationship between sequence variants and the repeated measurements of lung function parameters. In total, we genotyped 72 SNPs in 10 genes. Twenty-five SNPs were used for statistical analysis, where we found strong associations for one SNP in PPP2R4 with the lung clearance index (P≤0.01), the specific effective airway resistance (P≤0.005) and the forced expiratory volume in 1 s (P≤0.005). In addition, we identified one SNP in SNAP23 to be significantly associated with three lung function parameters as well as one SNP in PPP2R1A and three in KRT19 to show a significant influence on one lung function parameter each. Our findings indicate that direct interacters with CFTR, such as SNAP23, PPP2R4 and PPP2R1A, may modify the residual function of p.Phe508del-CFTR while variants in KRT19 may modulate the amount of p.Phe508del-CFTR at the apical membrane and consequently modify CF disease.     

Assessment of peripheral lung mechanics

The mechanical properties of the lung periphery are major determinants of overall lung function, and can change dramatically in disease. In this review we examine the various experimental techniques that have provided data pertaining to the mechanical properties of the lung periphery, together with the mathematical models that have been used to interpret these data. These models seek to make a clear distinction between the central and peripheral compartments of the lung by encapsulating functional differences between the conducing airways, the terminal airways and the parenchyma. Such a distinction becomes problematic in disease, however, because of the inevitable onset of regional variations in mechanical behavior throughout the lung. Accordingly, lung models are used both in the inverse sense as vehicles for extracting physiological insight from experimental data, and in the forward sense as virtual laboratories for the testing of specific hypothesis about mechanisms such as the effects of regional heterogeneities. Pathologies such as asthma, acute lung injury and emphysema can alter the mechanical properties of the lung periphery through the direct alteration of intrinsic tissue mechanics, the development of regional heterogeneities in mechanical function, and the complete derecruitment of airspaces due to airway closure and alveolar collapse. We are now beginning to decipher the relative contributions of these various factors to pathological alterations in peripheral lung mechanics, which may eventually lead to the development and assessment of novel therapies.