自由基在矽肺发病机制中的作用

为探讨自由基在矽肺发病机制中的作用,叙述了自由基的来源及其对肺巨噬细胞(AM)和细胞因子分泌、肺内其他生物基质、免疫的作用.石英在粉碎过程中自身可产生自由基;当AM吞噬石英和游走时引起"呼吸爆发",可产生大量自由基;髓单核细胞在肺中转化为AM后被活化时还可产生氮氧自由基.自由基作用于AM,产生脂质过氧化导致质膜损伤,进而分泌多种细胞因子,诱导纤维细胞增生和胶原合成,造成肺纤维化.自由基还可以作用于肺内其他生物基质和对免疫功能发生影响,促进肺纤维化过程.可见,自由基在矽肺发病机制中具有重要作用.     

石英所致红细胞脂质过氧化的自由基种类的初步探讨

本文利用酶学方法观察石英诱发红细胞脂质过氧化的自由基种类。在石英诱发红细胞脂质过氧化反应中,分别加入超氧化物歧化酶、过氧化物酶,结果提示这两种酶均不能减弱石英对红细胞的脂质过氧化作用。表明这个反应中,可能没有这两种酶所作用的底物自由基超氧阴离子(O_2~÷)与过氧化氢(H_2O_2)。抗氧化剂维生素E能减弱石英所致红细胞脂质过氧化作用。聚-2-乙烯吡啶氮氧化物能消除石英所致红细胞脂质过氧化作用。     

茶多酚对肺泡巨噬细胞脂质过氧化和抗氧化酶影响的实验研究

为探讨茶多酚抗石英尘细胞毒作用及其作用机理,采用体外细胞培养方法,观察了茶多酚对肺泡巨噬细胞( AM) 膜通透性、膜脂质过氧化、AM 内抗氧化酶活性的影响。结果表明,在体外染石英尘AM 中加入茶多酚,可以明显减少AM 释放乳酸脱氢酶(LDH) ,提高AM 内超氧化物歧化酶(SOD) 活性,且有剂量反应关系。茶多酚能显著抑制AM 膜丙二醛( MDA) 生成量,其中以20μg/ ml 茶多酚作用最为明显,而40μg/ ml 茶多酚作用有所减弱,可能与其高浓度下自氧化有关。说明茶多酚具有拮抗石英细胞毒性的作用,提示与其抗氧化功能有关     

抗氧化剂预防性治疗实验矽肺初探

自从发现SiO_2与肺泡巨噬细胞(AM)一起培养,培养物中脂质过氧化产物丙二醛(MDA)增加以来,许多学者认为SiO_2可能通过自由基机制诱导脂质过氧化(LPO)损伤AM。近来国内学者也涉入这个领域。本文利用抗氧化剂预防性治疗实验     

石英引起肺纤维化的早期细胞反应

多形核白细胞(PMN)及肺泡巨噬细胞(AM)被视为肺的防御细胞。在石英引起肺纤维化过程中,由于能释放PMN趋化因子及其他致纤维化因子,AM起到了关键的作用。对于石英引起的细胞反应,特别是在暴露于矽尘的早期阶段,还有许多问题有待探讨。我们研究了肺泡腔及肺组织细胞对矽尘作用的早期反应的动态变化,观察了石英引起的细胞间的相互作用。     

肺表面活性物质对在石英毒作用下肺泡巨噬细胞功能的影响

本文报告用体外实验方法,观察肺表面活性物质主要成份卵磷脂、脑磷脂对在石英毒作用下的肺泡巨噬细胞的影响。结果表明,卵磷脂可以明显地保护石英毒作用下的肺泡巨噬细胞,而脑磷脂无这种保护作用。卵磷脂的保护作用,可能与抑制肺泡巨噬细胞在石英作用下产生活性氧,抑制脂质过氧化反应有关,并间接证明活性氧自由基对肺泡巨噬细胞有损伤作用。     

电子自旋共振检测二氧化硅水悬液中羟基自由基的形成及其在矽肺脂质过氧化中的意义

有关二氧化硅导致肺纤维化的机理,至今尚远未阐明。目前,对于二氧化硅膜损伤作用特别是脂质过氧化反应,在矽肺发生中的作用较为关注。为了进一步阐明二氧化硅导致脂质过氧化的机理,本文首次用电子自旋共振(ESR)自旋捕获技术,检测了二氧化硅水悬液中自由基的形成。     

医院获得性肺炎克雷伯菌性肺炎患者脂质过氧化损伤的研究

目的探讨医院获得性肺炎克雷伯菌性肺炎患者体内的氧自由基损伤. 方法对呼吸加强病房20例医院获得性肺炎克雷伯菌性肺炎患者血清脂质过氧化氢(LHP)水平、血清谷胱甘肽过氧化物酶(GSH-PX) 及血清3种超氧化物歧化酶(SOD)进行测定, 并与对照组进行比较. 结果克雷伯菌性肺炎组LHP明显高于健康对照组, 两组比较差异非常显著(t=7.8901, P<0.01);GSH-PX水平明显低于对照组, 两组比较差异非常显著(t=9.9810, P<0.01);SOD T、SOD Cu-Zn、SOD Mn水平明显低于对照组, 两组比较差异非常显著(t=7.8546, t=10.3378, t=5.2179, 均P<0.01). 结论医院获得性肺炎克雷伯菌性肺炎患者体内存在由自由基介导的脂质过氧化损伤,这种脂质过氧化损伤参与了肺炎克雷伯菌性肺炎的病理过程;在治疗中合理使用自由基清除药物可能提高临床疗效.     

维生素E对矽肺血清过氧化脂质水平的影响

主要存在于细胞膜和细胞器磷脂内的多不饱和脂肪酸(PUFA),易受自由基攻击而发生脂质过氧化。近年来研究表明,它与多种疾病的发生有关。有人提出,SiO_2对肺泡巨噬细胞(AM)的毒性作用,是由于脂质过氧化反应增高而使溶酶体膜破坏。过氧化脂质(LPO),是脂质过氧化反应中形成的一类过氧化物,通常可以LPO水平来评价生物体过氧化反应的程     

电子自旋共振检测二氧化硅水悬液中羟基自由基的形成及其在矽肺脂质过氧化中的意义

有关二氧化硅导致肺纤维化的机理,至今尚远未阐明。目前,对于二氧化硅的膜损伤作用特别是诱发脂质过氧化反应,在矽肺发生中的作用较为关注。为了进一步阐明二氧化硅导致脂质过氧化的机理,本文首次用电子自旋共振(ESR)技术(自旋捕获),检测了二氧化硅水悬液中自由基的形成。结果表明,在新鲜配制     

石英尘对大鼠脂质过氧化与抗氧化作用的影响

利用染石英尘大鼠作为实验模型，比较支气管肺泡冲洗液（ＢＡＬＦ）、肺泡巨噬细胞（ＡＭ）中脂质过氧化产物和抗氧化物质的动态变化．结果表明，石英可以诱发ＡＭ脂质过氧化，在ＢＡＬＦ和ＡＭ中脂质过氧化产物（ＬＰＯ）的变化呈一致的趋势，但抗氧化物质的变化不完全相同．超氧化物歧化酶（ＳＯＤ）在ＢＡＬＦ和ＡＭ中活性均降低，说明石英可使其ＡＭ内该酶大量消耗或对该酶的活性有抑制作用．而还原型谷膛甘肽（ＧＳＨ）和谷胱甘肽过氧化物酶在ＡＭ内降低，但在ＢＡＬＦ中升高，说明石英对这两项指标无直接的影响，在ＡＭ内的降低是与从细胞内外漏入肺泡有关．     

矽肺,煤矽肺患者肺泡巨噬细胞的氧化和抗氧化系统

本文观察了不同时期矽肺、煤矽肺患者肺泡巨噬细胞化学发光、脂质过氧化物及超氧化物歧化酶的改变。结果表明,矽肺、煤矽肺患者肺泡巨噬细胞活性氧产生增加,脂质过氧化物含量增加。当患者肺泡巨噬细胞在体内重新受到石英粉尘刺激时,活性产生无变化,说明患者肺泡巨噬细胞由于长期受肺泡内或肺泡巨噬细胞内粉尘的作用,一直处于应激状态;而超氧化物歧化酶活性的升高,也证明了患者肺泡巨噬细胞处于代偿状态。进一步说明了活性氧自由基在矽肺的发展过程中起着重要的作用。     

Prevention of asbestos-induced cell death in rat lung fibroblasts and alveolar macrophages by scavengers of active oxygen species

Cell injury and inflammation caused by asbestos are critical to the pathogenesis of pulmonary fibrosis (asbestosis). Our goal in studies here was to investigate the possible modulation of asbestos-related cell death using antioxidants in both target and effector cells of asbestosis. After exposure to crocidolite asbestos at a range of concentrations (2.5-25 micrograms/cm2 dish), the viability of a normal rat lung fibroblast line (RL-82) and freshly isolated alveolar macrophages (AM) was determined by exclusion of trypan blue and nigrosin, respectively. In comparison to fibroblasts, AM were more resistant to the cytotoxic effects of asbestos. Cytotoxic concentrations of asbestos then were added to both cell types in combination with the antioxidants, superoxide dismutase (SOD), a scavenger of superoxide (O2-.), and catalase, an enzyme scavenging H2O2. Dimethylthiourea (DMTU), a scavenger of the hydroxyl radical (OH.) and deferoxamine, an iron chelator, also were evaluated in similar studies. Results showed significant dosage-dependent reduction (P less than 0.001) of asbestos-associated cell death with all agents. In contrast, asbestos-induced toxicity was not ameliorated after addition of chemically inactivated SOD and catalase or bovine serum albumin. Results above suggest asbestos-induced cell damage is mediated by active oxygen species. In this regard, the iron associated with the fiber and/or its interaction with cell membranes might be critical in driving a modified Haber-Weiss (Fenton-type) reaction resulting in production of OH(.).     

Active smoking causes oxidative stress and decreases blood melatonin levels

Oxidative effects via free radical generation in smokers have been widely investigated. They cause lipid peroxidation, oxidation of proteins and damage to mainly lung and other tissues. In humans, antioxidative capacity of serum is related to antioxidant enzymes superoxide dismutase (SOD), glutathione peroxidase (GSH-Px) and melatonin. The effect of cigarette smoking on plasma levels of melatonin and antioxidant enzymes has not been established together yet. Also, it may not be clear if melatonin levels are affected by smoking and melatonin has a protective effect on cigarette smoking-induced free radical damage. The aim of this study is to investigate the relationship between smoking and antioxidant capacity including melatonin, a powerful endogenous antioxidant, and antioxidant enzymes in teenage girls who are active smokers. Additionally, malondialdehyde (MDA) levels were determined in those who have smoked at least one packet a day for three or more years. MDA levels have been used as a convenient index of the lipid peroxidation-related oxidative damage of tissues. Twenty-one young female active smokers who study at the School of Nursing and 21 nonsmoking students (as controls) at the same school were included in the study. The activities of two principal antioxidant enzymes SOD, GSH-Px and plasma levels of MDA were significantly increased but melatonin content of the blood was significantly decreased as compared to nonsmokers. In spite of an increase in antioxidant enzyme activities, MDA levels were slightly increased in smokers. This indicates that antioxidant self-defence mechanisms may not sufficiently protect the respiratory system from smoke-mediated oxidative injury. This result may be related to low melatonin levels in teenage female smokers. It seems that melatonin can reduce free radical damage to the respiratory system induced by cigarette smoke. Further experimental investigations with exogenous melatonin treatments will be needed.     

石英对细胞内游离钙.镁的影响

用荧光染料Fura-2测定了家兔肺泡巨噬细胞(AM)和人红细胞(RBC)胞浆游离钙离子浓度([Ca~(2 )]_1),用furaptra测定了AM胞浆游离镁离子浓度([Mg~(2 )]_1)。石英对AM和RBC的毒性导致[Ca~(2 )]_1增加,作用时间越长,[Ca~(2 )]_1增加越多。同样条件下,染石英尘后的AM[Mg~(2 )]_1和脂质过氧化物(LPO)值也升高。以上结果提示石英可能破坏了细胞膜的结构和功能,以致细胞外Ca~(2 )和Mg~(2 )内流。卵磷脂、PVPNO和柠檬酸铝可拮抗石英引起的脂质过氧化作用和[Ca~2 ]_1及[Mg~2 ]_1的增加。卵磷脂有可能用于预防石英粉尘的毒作用。     

Effect of quartz and alumina dust on generation of superoxide radicals and hydrogen peroxide by alveolar macrophages, granulocytes, and monocytes.

Phagocytosis of quartz particles by rabbit alveolar macrophages and monocytes and human granulocytes and monocytes was accompanied by stimulation of substrate free reduction of nitroblue tetrazolium to formazan. This reflects activation of an oxygen dependent bactericidal system of phagocytes and total (exogenic and endogenic) generation of active oxygen species. Low fibrogenic and cytotoxic alumina dust tended to increase formazan production by comparison with quartz dust. During phagocytosis of quartz dust by alveolar macrophages and monocytes there was no exogenic generation of superoxide radicals and hydrogen peroxide by these cells. By contrast, incubation of human granulocytes with quartz dust caused a significant increase in exogenic generation of superoxide radicals and hydrogen peroxide. Under such conditions, low fibrogenic alumina dust had no effect on hydrogen peroxide generation and substantially decreased the level of superoxide radical generation by human granulocytes. During incubation of rabbit granulocytes with quartz dust, an increase in the level of superoxide radical generation was also detected. It is considered that the differences between alveolar macrophages and granulocytes in their response to quartz dust are important from a physiological point of view. Alveolar macrophages are permanently present in pulmonary alveolae in large quantities; therefore their uncontrolled generation of superoxide radicals and hydrogen peroxide might immediately cause damage to pulmonary parenchyma. At the same time, destruction products from alveolar macrophages that died during phagocytosis of quartz particles contain a factor attracting granulocytes. Presence of a significant number of granulocytes in bronchopulmonary lavage fluid in cases of silicosis indicates development of a pathological process. This agrees well with the data obtained on exogenic generation of superoxide radicals and hydrogen peroxide by granulocytes, and on stimulation of this process due to phagocytosis of the quartz dust.     

维生素E联合维生素C对染石英尘肺泡巨噬细胞脂质过氧化和抗氧化酶的影响

目的 探讨维生素E与维生素C联合抗石英尘细胞毒作用及其机制。方法 采用体外细胞培养法，研究不同浓度维生素E与维生素C对染色英尘的肺泡巨噬细胞（AM）膜脂质过氧化和抗氧化酶的影响。结果 在染石英尘的AM中加入维生素E与维生素C，可以减少活性氧，丙二醛的生成，与石英组比较，差异有显著性；而过氧化氢酶，谷胱甘肽过氧化物酶，超氧化物歧化酶的活力和细胞活力高于石英组。结论 维生素E联合维生素C对染石英尘的肺泡巨噬细胞具有保护作用。     

宁夏枸杞对密闭缺氧小鼠自由基防御体系的影响

用枸杞匀浆水提液给小鼠灌胃 16天 ,进行密闭急性缺氧实验。结果表明 :在本实验条件下 ,枸杞不能延长密闭缺氧小鼠的生存空间 (P >0 0 5 ) ,但是能明显提高小鼠心、肝、肺组织超氧化物歧化酶、过氧化氢酶活性和总抗氧化能力。从而提示 ,宁夏枸杞对急性缺氧小鼠自由基损伤可能有一定保护作用。     

镉染毒后肾小管上皮细胞内氧自由基代谢与损伤之间关系的研究

本文以离体肾小管上皮细胞为研究对象，观察了镉致肾小管上皮细胞损伤时细胞内氧自由基反应及其与细胞超微结构改变之间的关系。结果表明，镉可诱发离体肾小管上皮细胞脂质过氧化反应增强，脂质过氧化产物明显增加，超氧化物歧化酶及过氧化氢酶活性显著受抑，与此同时肾小管细胞出现一系列超微结构改变；抗氧化剂ＶｉｔＥ可使脂质过氧化作用明显减弱。提示镉臻肾小管上皮细胞损伤与氧自由基对细胞膜结构及功能的损伤有关，氧自由基在