阻塞性睡眠呼吸暂停与心血管疾病

本文分析关于阻塞性睡眠呼吸暂停与心血管疾病之间的关系、发生发展机制的最新进展,阐述对阻塞性睡眠呼吸暂停合并心血管疾病的患者行经鼻气道持续正压通气治疗能给患者心血管疾病的治疗、预后、康复和生活质量带来益处.本篇综述的目的 在于引起医务工作者对阻塞性呼吸暂停与心血管疾病的关系的重视,从而服务于临床.     

经鼻持续气道正压通气对阻塞性睡眠呼吸暂停综合征的综合疗效

经鼻持续气道正压通气（CPAP）是目前治疗阻塞性呼吸暂停综合征（OSAS）最有效的内科治疗方法,通过向气道内增加一定程度的正压,保持上气道通畅,消除患者夜间缺氧,改善患者夜间打鼾,白天嗜睡等临床症状,恢复睡眠结构,并治疗与此相关的各系统疾病,提高患者长期的生活质量。     

持续气道正压通气对阻塞性睡眠呼吸暂停患者睡眠结构的影响

目的探讨患者白天嗜睡等症状的原因,评估经鼻持续气道内正压通气(nCRAP)治疗对阻塞性睡眠呼吸暂停患者睡眠结构的影响。方法选择2001-2004年广东省佛山市第一人民医院呼吸科34例OSAS病人在睡眠多导生理记录仪监测下,进行nCPAP治疗,观察治疗前后呼吸紊乱指数、血氧饱和度和睡眠结构的变化。结果治疗后呼吸紊乱指数下降,最低血氧饱和度上升,睡眠结构明显改善。结论nCRAP能有效地改善OSAS病人的睡眠结构和呼吸紊乱。     

阻塞性睡眠呼吸暂停与卒中

睡眠呼吸障碍(sleep disordered breathing, SDB)与卒中之间的联系最早在19世纪提出,但直到1980才开始得到广泛关注.目前,卒中仍然是重要的死亡原因.同时,卒中也与其他慢性疾病的发病率息息相关.在过去的20年中,对于阻塞性睡眠呼吸暂停(obstructive sleep apnea, OS...     

经鼻持续气道正压通气治疗阻塞性睡眠呼吸暂停综合征的依从性分析

目的了解经鼻持续气道正压通气（nCPAP）治疗阻塞性睡眠呼吸暂停综合征（OSAS）的依丛性及其影响因素。方法对经nCPAP治疗的40例OSAS患者进行随访调查,分析性别、年龄、职业、教育程度、病程、对疾病的认知程度、家族史、治疗前后临床表现、nCPAP治疗压力以及使用呼吸机过程中出现副作用等因素,结合对治疗效果的自我评价和睡眠监测等指标,计算其依从性,并用多元回归方法统计分析上述因素与依从性之间的关系。结果nCPAP治疗OSAS的依从性为（80．18±23．65）％,以依从性为因变量,以上述因素为自变量作多元逐步回归分析,在α=0．05的水平上,进入回归方程的有4个因素,按作用强度大小依次为治疗效果、打鼾程度、对疾病认知程度和使用呼吸机过程中有无出现副作用及其他问题。结论nCPAP治疗OSAS有较高依从性。治疗效果、打鼾程度、对疾病认知程度和使用呼吸机过程中有无出现副作用对依从性有较大影响。     

特发性肺纤维化与阻塞性睡眠呼吸暂停

人一生中有近三分之一的时间在睡眠中度过,睡眠在人类日常生活中有着重要作用.睡眠可增强免疫力,睡眠时各种组织器官的自我修复加快,有利于疾病的康复;睡眠时机体的生长激素水平升高,有利于生长发育;睡眠时人体基础代谢率降低,有利于精力、体力的恢复.阻塞性睡眠呼吸暂停(obstructive sleep apnea,OSA)是常...     

阻塞性睡眠呼吸暂停低通气综合征导致心血管疾病相关机制

阻塞性睡眠呼吸暂停低通气综合征的发病率逐年增加,人们逐渐认识到阻塞性睡眠呼吸暂停低通气综合征是一种会引起全身多系统损伤的疾病.大量研究证实阻塞性睡眠呼吸暂停低通气综合征与包括高血压、冠心病、心律失常、心力衰竭等在内的心血管疾病之间具有显著相关性.本文针对胸腔负压改变、自主神经紊乱、氧化应激及炎症反应、细胞凋亡等阻塞性睡...     

福州城镇男性阻塞性睡眠呼吸暂停低通气综合征患者睾酮水平研究

目的 研究福州城镇男性阻塞性睡眠呼吸暂停低通气综合征(OSAHS)患者的血清睾酮水平及经鼻持续气道正压通气(nCPAP)治疗对OSAHS患者血清睾酮水平的影响.方法 182例入选者经多导睡眠监测,按年龄分25～45岁、46～65岁两层,再按睡眠呼吸紊乱严重程度进行分组:分别为正常对照组(20例、21例)、单纯性鼾症组(14例、13例)、轻度OSAHS组(21例、17例)、中度OSAHS组(19例、19例)、重度OSAHS组(18例、20例).在多导睡眠监测次晨抽取外周静脉血用电化学发光法测定血清睾酮.对比正常对照组、单纯性鼾症组、OSAHS组间睾酮水平的差异,分析睾酮水平与睡眠呼吸紊乱指数(AHI)、体质量指数(BMI)之间的相关性.开展nCPAP干预实验,对接受/未接受nCPAP治疗的中重度OSANS患者随访3个月,复查多导睡眠监测及血清睾酮指标.结果 ①正常对照组与单纯性鼾症组2组间血清睾酮差异无统计学意义(P值均＞0.05).OSAHS组血清睾酮较正常对照组及单纯性鼾症组低.②睾酮与AHI、BMI、年龄均呈负相关(r=-0.589,P＜0.01;r=-0.225;P＜0.05;r=-0.454,P＜0.01),睾酮与最低SaO2呈正相关(r=0.459,P＜0.01).③中重度OSAHS患者中,接受nCPAP治疗者随访3个月后,血清睾酮水平升高(P＜0.01).未接受nCPAP治疗者随访3个月后,血清睾酮水平无明显变化(P＞0.05).结论 ①OSAHS患者血清睾酮水平低,血清睾酮水平与AHI、BMI呈负相关.②OSAHS患者血清睾酮水平随年龄增加而降低.③nCPAP治疗可改善OSAHS患者血清睾酮水平.

Abstract：

Objective To explore the testosterone levels in Fuzhou urban male patients with obstructive sleep apnea-hypopnea syndrome (OSAHS) and impact of nasal continuous positive airway pressure (nCPAP) treatment. Methods Following polysomnographic examination, 182 sbjucts were assigned to 25-45years and 46-65years two groups. Each group consist of:control group(20,21 case), simple snores(14,13case), mild OSAHS(21,17case) ,moderate OSAHS(19,19 case),and severe OSAHS (18,20case). The serum level of testosterone was measured after sleep at the polysomnographic examination night. Of 76 patients with moderate or severe OSAHS, 29 patients who underwent nCPAP therapy were set as "nCPAP group" ,47 patients who did not undergo nCPAP therapy were set as "control group". 10 patients were excluded from further follow-up. The assessment protocol was then repeated after 3 months follow-up. Results ①There were no statistically significant differences of the serum level of testosterone between simple snores and control group. The serum level of testosterone was significantly lower in OSAHS patient. ② Liner regression analysis showed the serum level of testosterone was negatively correlated with AHI, BMI, year( r = -0.589, P ＜0. 01; r = -0.225, P ＜0.05; r = - 0.454, P＜0. 01), testosterone was correlated with SaO2 ( r =0.459, P ＜0.01). ③After 3 months nCPAP therapy in OSAHS patients, the serum level of testosterone was significantly increased ( P ＜ 0.01). While there were no similar changes in OSAHS patients without nCPAP therapy( P >0. 05). Conclusions ①OSAHS patients have lower level of testosterone. The serum level of testosterone was negatively correlated with AHI,BMI. ②As the age older,the serum level of testosterone lower in OSAHS patients. ③The serum level of testosterone could be improved by nCPAP therapy in OSAHS patients.     

经鼻持续气道内正压通气治疗阻塞性睡眠呼吸暂停低通气综合征进展

阻塞性睡眠呼吸暂停低通气综合征(OSAHS)是一种发病率较高并具有一定潜在危险的疾病,经鼻持续气道内正压通气(nCPAP)目前已成为治疗中、重度OSAHS患者的首选措施。本文介绍了应用nCPAP的治疗机制、对各器官的治疗作用、压力水平的调节、影响其成功的因素、以及经鼻面罩正压机械通气治疗OSAHS新模式和治疗的副作用等进行了综述。     

阻塞性睡眠呼吸暂停综合征与难治性高血压

阻塞性睡眠呼吸暂停综合征(OSAS)与难治性高血压关系密切,它可通过交感神经兴奋增强、内皮功能损伤、肾素-血管紧张素-醛固酮系统紊乱等机制引起血压增高,而且临床表现有自己的特点。因此,对于难治性高血压患者应注意有无OSAS以及是否给予了相应治疗。     

细胞外反应激酶信号传导通路及其在心肌肥厚中的作用

细胞外反应激酶是细胞内广泛存在的有丝分裂原激活的蛋白激酶超家族成员 ,通过受体酪氨酸激酶通路和异三聚体 G蛋白耦连的受体通路两条途径激活 ,直接参与心肌肥厚的启动、诱发心肌细胞肥大的形态学改变 ,调控基因表达 ,在心肌肥厚的发生、发展过程中具有促进作用。     

Translational evidence on the role of Src kinase and activated Src kinase in invasive breast cancer

Src kinase is a member of a non-receptor tyrosine kinase family. It has been implicated as a regulator of cell proliferation and survival and plays a complex role in cell adhesion and motility. In vitro evidence for a role for Src in breast cancer is compelling. However, only a few translational clinical studies have been undertaken in this field. This review summarises translational evidence on expression and activation of Src kinase in breast cancer patient cohorts exploring clinical significance and the possibility of identifying key biomarkers. There is strengthened translational proof for a definitive role of Src in breast cancer. Nevertheless, there remains a need to find a robust biomarker to identify patients responsive to Src inhibitors for clinical trials.     

整合素在心肌肥大细胞信号转导中的作用

整合素及其信号转导通路在心脏的发育和心肌肥大的发生与发展中起着重要作用,作为介导心肌肥大的细胞表面受体的异二聚体家族,为细胞黏附提供附着点,通过其双向信号转导通路和机械传导受体作用,调节下游信号转导蛋白的磷酸化水平与活性,调整心肌细胞骨架的重构.其中报道较多的是β1整合素及其相关的信导分子以及少量的关于 β3整合素及其...     

高血压大鼠左心室肥大心肌细胞中Src激酶膜转位的研究

目的:探讨Src激酶在高血压所致左心室肥大发病机制中的作用。方法: 以自发性高血压大白鼠(SHR)为研究对象,通过免疫荧光标记、共聚焦显微镜观察及蛋白质印迹等方法,检测不同月龄的SHR左心室肥大心肌细胞中Src激酶的表达和定位的变化。结果: 蛋白质印迹检测显示,Src激酶在2、6、12和18月龄的SHR组左心室心肌组织抽提的总蛋白匀浆中的表达量与相同月龄的对照Wistar-kyoto(WKY)大鼠组相比较,无明显变化;而在其抽提的胞质蛋白匀浆中和膜蛋白匀浆中,2月龄的SHR组与对照WKY大鼠组相比较,Src激酶的表达无明显差别,但将6、12、18月龄的SHR组分别与相同月龄的WKY大鼠组比较,在胞质蛋白匀浆中Src激酶的表达显著减少(P<0.05),在膜蛋白匀浆中Src的表达则显著增加(P<0.05)。免疫荧光标记也显示,在6、12和18月龄的SHR心肌细胞中出现一些定位变化,主要表现为Src激酶在心肌细胞闰盘的聚集,在心肌细胞闰盘处可观察到较宽的明亮荧光带,这些变化正好与SHR左心室肥大心肌细胞失代偿性重构相吻合。结论:研究结果表明,在高血压所致失代偿性心肌肥大形成和发展的全过程中,存在Src激酶的膜转位,提示心肌细胞中Src激酶信号转导通路可能参与了高血压所致失代偿性左心室肥大的心肌重构过程。     

Src及其抑制剂对非小细胞肺癌作用的研究进展

Src酪氨酸激酶家族是非小细胞肺癌（NSCLC）细胞生存、增生、游走和黏附的关键调控点。Src可被黏着斑激酶（FAK）、表皮生长因子（EGF）、肝细胞生长因子（HGF）、血小板衍生生长因子（PDGF）等激活并参与多条信号转导途径。Src的过度激活在NSCLC的发生、发展和转移过程中起着非常重要的作用。Src抑制剂-Dasatinib、AZD0530、SKI-606、XL999和M475271的体外实验和临床应用有抑制NSCLC的作用。     

Expression of Src and FAK in hepatocellular carcinoma and the effect of Src inhibitors on hepatocellular carcinoma in vitro

The expressions of c-Src and focal adhesion kinase (FAK) were studied in 65 Chinese patients with hepatocellular carcinoma (HCC) by immunohistochemistry using rabbit monoclonal antibodies. Expressions of total Src, an active form of Src, and FAK were found in 44/65 (67.7%), 36/45 (55.4%), and 33/56 (58.9%) HCC cases, respectively. There was a good correlation between the expression of total Src, active form of Src, and FAK in these HCC cases (P < 0.001). Expression of Src was not correlated to any clinical parameters, cancer cell phenotypic markers, and pathologic features apart from a positive correlation with alpha-fetoprotein (P < 0.01). The expression of FAK was correlated with earlier onset and the expression of Ki-67 but not proliferating cell nuclear antigen (PCNA) in these HCC cases. Four liver-cancer-derived cell lines (three derived from HCC and one from hepatoblastoma) were then tested with inhibitors against Src. A small molecule, KX2-391, designed to target the substrate binding pocket of Src, was found to have more broad-spectrum activity and better potency than Dasatinib, an adenosine triphosphate (ATP)-competitive inhibitor in vitro. Our data indicates that Src and FAK expression are both elevated and active in Chinese patients with HCC and that Src may play a key role in supporting HCC progression. Src antagonism with specific inhibitors may be an attractive treatment paradigm for patients with HCC.     

Src激酶在胃癌细胞来源的exosome促进肿瘤细胞增殖中的作用

目的:研究胃癌细胞来源的外泌体(exosome)对肿瘤细胞增殖的影响,初步探讨Src蛋白激酶在此过程中的作用.方法:采用离心超滤和蔗糖密度梯度超速离心的方法从胃癌SGC7901细胞的上清液中分离出胃癌细胞来源的exosome.透射电子显微镜下观察exosome形态.MTT法检测细胞增殖能力,Western blot检测...     

The Src family kinase Hck regulates mast cell activation by suppressing an inhibitory Src family kinase Lyn

IgE/antigen-dependent mast cell activation plays a central role in immediate hypersensitivity and other allergic reactions. The Src family tyrosine kinase (SFK) Lyn is activated by the cross-linking of high-affinity IgE receptors (FcRI). Activated Lyn phosphorylates the FcRI subunits, ß and , leading to subsequent activation of various signaling pathways. Lyn also plays a negative regulatory function by activating negative regulatory molecules. Another SFK, Fyn, also contributes to mast cell degranulation by inducing Gab2-dependent microtubule formation. Here we show that a third SFK, Hck, plays a critical role in mast cell activation. Degranulation and cytokine production are reduced in FcRI-stimulated hck^–/– mast cells. The reduced degranulation can be accounted for by defects in Gab2 phosphorylation and microtubule formation. Importantly, Lyn activity is elevated in hck^–/– cells, leading to increased phosphorylation of several negative regulators. However, positive regulatory events, such as activation of Syk, Btk, JNK, p38, Akt, and NF-B, are substantially reduced in hck^–/– mast cells. Analysis of lyn^–/–hck^–/–, lyn^–/–FcRIß^–/–, and hck^–/–FcRIß^–/– cells shows that Hck exerts these functions via both Lyn-dependent and Lyn-independent mechanisms. Thus, this study has revealed a hierarchical regulation among SFK members to fine-tune mast cell activation.