肝移植术后危重患者血浆脂质过氧化物的变化及意义

目的　研究肝移植患者术后血浆中脂质过氧化物 (L PO)与术后病情变化的关系。方法　测定了18例肝移植患者术后 2 1d内血浆中 L PO的水平 ,分析其与预后的关系。结果　血浆 L PO在病情明显恶化前有所升高 ,尤其在死亡组患者持续升高 ,其升高的峰值明显高于存活患者 ,血浆 L PO峰值超过 10 μmol/L 的患者死亡几率 (5 /6 )高于血浆 L PO峰值低于 10 μmol/L 的患者 (1/12 ) ,两组病死率差异有显著性意义(P<0 .0 1) ,血浆 L PO日变化率超过 1.2 μmol· L- 1· d- 1的患者死亡几率 (4/5 )高于血浆 L PO日变化率低于 1.2 μmol· L- 1· d- 1的患者 (2 /13) ,两组病死率差异有显著性意义 (P<0 .0 1)。结论　术后检测血浆 L PO对正确判断患者病情危重程度有重要的临床价值 ,可作为常规检查。     

高血压、冠心病患者测定脂质及载脂蛋白的意义

高血压、冠心病是我国的常见病,与血液中脂类代谢异常有关,近年来检测项目逐渐增多,为探讨各项检测项目在高血压(HPD)、冠心病(CHD)中的临床价值,现将67例HPD患者和66例CHD患者与92例健康人血清进行分析讨论,结果报告如下.     

儿童情绪障碍过氧化脂质及谷胱甘肽过氧化物酶的研究

目的了解儿童情绪障碍过氧化脂质(LPO)及谷胱甘肽过氧化物酶(GPX)水平,探讨其病因。方法测定30例儿童情绪障碍LPO及GPX水平与正常儿童(30例)比较研究。结果儿童情绪障碍LPO明显高于对照组(P<0.05)。结论LPO的改变可能是儿童情绪障碍的生物学原因之一。     

支气管哮喘患者氧化/抗氧化系统的变化及意义

支气管哮喘是一种多因素参与的慢性变态反应性气道炎性疾病,其基本的病理改变为嗜酸性粒胞、淋巴细胞、巨噬细胞、肥大细胞等炎性细胞浸润。这些炎性细胞聚集、激活过程中可产生大量的氧由基,引发了脂质过氧化作用,加重了炎症反应成组织损伤。因此氧化应激反应在支气管哮喘中的     

绞股蓝皂甙抗自由基损伤作用的实验研究

绞股蓝皂甙在自由基损伤大鼠模型上,抑制肝脏和血浆的脂质过氧化反应,显著降低老年大鼠肝脏脂质过氧化物含量。在体外条件下,不同程度地抑制肝脏脂质过氧化作用。绞股蓝皂甙还能增加自由基损伤模型大鼠和老年大鼠红细胞超氧化物歧化酶活力。提示绞股蓝皂甙有抗氧化和抗自由基损伤作用,初步揭示其延缓衰老的生化基础。     

糖尿病患者超氧化物歧化酶和过氧化脂质的测定及临床意义

过氧化脂质（Lipid Peroxidation LPO）是反映自由基对机体损伤的指标,超氧化物歧化酶（Superoxide Dismutase SOD）是生理状态下机体存在的防止自由基反应的酶,它能清除自由基,保护机体免受自由基的损伤。对糖尿病患者血浆中过氧化脂质和红细胞中超氧化物歧化酶进行了测定,发现糖尿病患者体内存在着自由基反应损伤,这为临床治疗和研究糖尿病提供参考。     

纳洛酮对颅脑损伤后细胞凋亡及自由基影响的实验研究

目的观察纳洛酮对严重颅脑损伤后神经细胞凋亡及血红细胞内超氧化物歧化酶(SOD)及体内脂质过氧化物(LPO)的影响,探讨纳洛酮抗神经细胞凋亡的自由基机理. 方法选用健康普通家兔随机分成对照组和纳洛酮组,分别予致伤和致伤后纳洛酮腹腔注射处理,在致伤后0、6h、1、3、7、11d和15d检测血红细胞内SOD及LPO浓度,在致伤后15d检测脑组织中凋亡神经细胞数量. 结果纳洛酮组家兔脑组织凋亡神经细胞显著少于对照组(P<0.05);在7个时间段,纳洛酮组家兔血红细胞内SOD活性和LPO含量与对照组没有显著性差异(P>0.05). 结论纳洛酮可抑制严重颅脑损伤后神经细胞凋亡,自由基可能不参与作用过程.     

红景天对衰老小鼠脑过氧化脂质及线粒体超微结构的影响

背景衰老是生物体内各组织、器官的退行性改变,是诸多病理、生理过程综合作用的结果.红景天是一种天然药用植物,具有延缓机体衰老、防治老年病等功能,但是其确切机制仍不十分清楚.目的探讨藏药红景天提取物(诺迪康胶囊)抗衰老作用及其机制.设计以实验动物为研究对象,随机对照的实验研究.单位一所军医大学医院的神经内科.材料实验于2002-03/08在解放军第四军医大学药理学实验室完成.60只昆明种小鼠随机分为正常对照组、模型组、诺迪康1,,4 g/kg3个剂量组、维生素E阳性对照组0.1 mg/kg,每组10只.干预模型组、诺迪康组、维生素E阳性对照组均将30 g/L D-半乳糖生理盐水溶液,按每日150mg/kg颈后部皮下注射,连续8周,同时,诺迪康组、维生素E阳性对照组灌胃给药,次/d,连续8周.主要观察指标诺迪康胶囊对衰老小鼠脑乳酸脱氢酶(lactate dehydrogenase,DH)活性、过氧化脂质(lipidperoxides,PO)含量,脑过氧化物歧化酶(superoxide dismutase,OD)活性、丙二醛(malondialdehyde,DA)含量以及海马神经元线粒体超微结构的影响.结果诺迪康胶囊1,,4 g/kg组均可降低脑组织LPO含量[(30.1±2.9),(27.8±3.1),26.9±1.9)nmol/g]和MDA含量[(110.2±13.5),(95.4±20.1),90.2±16.5)nmol/g],与模型组[(33.4±2.2),126.5±17.2)nmol/g]相比,差异均有显著性意义(P＜0.05);并明显升高LDH活性[(1.74±0.14),1.92±0.23),2.04±0.21)NU/g]和SOD活性[(119.1±2.2),121.3±0.9),126.4±2.0)NU/g],与模型组[(1.68±0.19),115.9±2.1)NU/g]相比,差异均有显著性意义(P＜0.05).电镜结果表明,诺迪康胶囊2, g/kg组对半乳糖引起的海马神经元线粒体退行性变具有明显的保护作用.结论诺迪康胶囊具有显著的抗衰老作用,此作用与其抗氧化损伤和保护神经元有关.     

两组中药复方影响前列腺癌细胞生长的体内外实验研究

目的 探讨两组中药复方对前列腺癌细胞PC-3 体内外生长的影响及其可能的作用机制.方法 以临床常用的抗癌中药组成两组复方(复方B:白花蛇舌草、半枝莲、土茯苓和莪术;复方C:白花蛇舌草、半枝莲、土茯苓、莪术、三棱和皂角刺),分别用等量生理盐水和两组复方的水煎剂对成年雄性去势SD 大鼠灌胃后取血制成空白对照(A 组)和含药血清(B、C组);三组血清加入PC-3 的细胞培养液,应用MTT 法、流式细胞术、Hoechst 染色法检测细胞存活率、细胞周期分布及凋亡的差异.建立BALB/C 裸鼠荷前列腺癌动物模型,分别用生理盐水和两组复方的水煎剂灌胃,观察裸鼠肿瘤生长情况,HE 染色观察肿瘤组织形态学变化,TUNEL 法检测肿瘤细胞凋亡情况,免疫组化染色法检测肿瘤组织中Ki-67 表达.结果 体外细胞培养实验中B 组的细胞存活率最低,且随着培养时间的增加而持续降低;C 组的细胞存活率较B 组高,但显著低于对照组;两个复方组的S 期细胞比例显著低于对照组,而G0/G1 期细胞比例显著高于对照组(均P ＜0.05);B 组和C 组的凋亡细胞比例约为30%和10%,均多于对照组.裸鼠体内实验中B 组的抑瘤率大于C 组的抑瘤率(23% vs.18%),B 组的平均瘤重最小,平均肿瘤体积最小;B 组的TUNEL 阳性率最高,Ki-67 阳性率最低.结论 两组中药复方在体外显著抑制PC-3 细胞增殖,同时诱导其凋亡,在体内也能抑制肿瘤生长;并且复方B 的抑瘤作用最强.     

使用GMA及PAS-Ⅲ2种添加液冷藏保存血小板的体外研究

目的比较2种不同添加液对4℃冷藏血小板的体外形态、活力和活化程度等指标的差异,分析特定的添加液对4℃冷藏血小板的保护作用。方法取8份单采血小板,将其一分为二,各保留35%血浆,分别添加葡萄糖甘露醇腺嘌呤血细胞保存添加液(GMA)和血小板保存添加液Ⅲ(PAS-Ⅲ)2种不同保存添加液,置4℃条件下保存,于5d后取样测定有关指标。结果在保存5d期间,GMA-PCs的低渗休克反应明显高于PAS-Ⅲ-PCs;而P-选择素的表达则显著低于后者;另外,前者IL-6的产生亦显著低于后者;2组PCs的血小板形变能力、GPⅠbα表达、乳酸生成无显著性差异。结论在4℃冷藏条件下采用血小板保存添加液替代血浆保存单采血小板,对保持血小板体外质量,GMA优于PAS-Ⅲ。     

Oxygen-derived free radicals stimulate osteoclastic bone resorption in rodent bone in vitro and in vivo.

The mechanisms by which bone resorbing osteoclasts form and are activated by hormones are poorly understood. We show here that the generation of oxygen-derived free radicals in cultured bone is associated with the formation of new osteoclasts and enhanced bone resorption, identical to the effects seen when bones are treated with hormones such as parathyroid hormone (PTH) and interleukin 1 (IL-1). When free oxygen radicals were generated adjacent to bone surfaces in vivo, osteoclasts were also formed. PTH and IL-1-stimulated bone resorption was inhibited by both natural and recombinant superoxide dismutase, an enzyme that depletes tissues of superoxide anions. We used the marker nitroblue tetrazolium (NBT) to identify the cells that were responsible for free radical production in resorbing bones. NBT staining was detected only in osteoclasts in cultures of resorbing bones. NBT staining in osteoclasts was decreased in bones coincubated with calcitonin, an inhibitor of bone resorption. We also found that isolated avian osteoclasts stained positively for NBT. NBT staining in isolated osteoclasts was increased when the cells were incubated with bone particles, to which they attach. We confirmed the formation of superoxide anion in isolated avian osteoclasts using ferricytochrome c reduction as a method of detection. The reduction of ferricytochrome c in isolated osteoclasts was inhibited by superoxide dismutase. Our results suggest that oxygen-derived free radicals, and particularly the superoxide anion, are intermediaries in the formation and activation of osteoclasts.     

Tanshinone (Salviae miltiorrhizae extract) preparations attenuate aminoglycoside-induced free radical formation in vitro and ototoxicity in vivo

Antioxidant therapy protects against aminoglycoside-induced ototoxicity in animal models. A clinically suitable antioxidant must not affect the therapeutic efficacy of aminoglycosides or exhibit any side effects of its own. In addition, the treatment should be inexpensive and convenient in order to be implemented in developing countries where the use of aminoglycosides is most common. Standardized Salviae miltiorrhizae extracts (Danshen) are used clinically in China and contain diterpene quinones and phenolic acids with antioxidant properties. We combined in vitro and in vivo approaches to investigate the effect of a clinically approved injectable Danshen solution on aminoglycoside-induced free radical generation and ototoxicity. In vitro, Danshen inhibited gentamicin-dependent lipid peroxidation (formation of conjugated dienes from arachidonic acid), as well as the gentamicin-catalyzed formation of superoxide (in a lucigenin-based chemiluminescence assay) and hydroxyl radicals (oxidation of N,N-dimethyl-p-nitrosoaniline). Danshen extracts were then administered to adult CBA mice receiving concurrent treatment with kanamycin (700 mg/kg of body weight twice daily for 15 days). Auditory threshold shifts induced by kanamycin (approximately 50 dB) were significantly attenuated. Danshen did not reduce the levels in serum or antibacterial efficacy of kanamycin. These results suggest that herbal medications may be a significantly underexplored source of antidotes for aminoglycoside ototoxicity. Such traditional medicines are widely used in many developing countries and could become an easily accepted and inexpensive protective therapy.     

Microbubble formation: In vitro and in vivo observation

Injection of liquid through a catheter into the circulation is known to produce clouds of signals detected by sonography. Blood forced through a stenotic conduit produced sonographic clouding, and bubbles of 10–100 μm were observed by light microscopy. The microbubbles persisted up to three and a half minutes. Microbubbles were observed in the microcirculation of the rat by placing the catheter tip into the descending aorta of 15 animals, viewing the mesentery at 400X magnification, and recording the results on videotape. Following injection of the rats' own blood, numerous microbubbles lodged promptly at the arteriolar level and obstructed blood flow for up to 200 sec before shrinking sufficiently to pass downstream and allow restitution of flow.     

Sonochemically induced radicals generated by pulsed high-energy ultrasound in vitro and in vivo.

The aim of this study was to evaluate the role of radicals as a mechanism of tissue damage induced by pulsed high-energy ultrasound. Transient cavitation has proved to be an important mechanism for the generation of reactive radical species during pulsed high-energy ultrasound applications. The amount of radicals studied in in vitro experiments using a chemical dosimeter based on iodine release is proportional to the number of pulses. Sonications of the R3327-AT1 subline of the Dunning prostate rat tumor transplanted in the thigh of Copenhagen rats were performed applying 500 and 2000 pulses at a pulse repetition frequency of 1 Hz. Tumor growth after treatment was compared with sham-treated controls. We were able to assess a significant growth delay, but could not find a significant difference between the two groups treated. In conclusion, radical formation does not seem to be the major mechanism for tissue necrosis induced by pulsed high-energy ultrasound.     

Ageing and free radicals.

Mammalian ageing is a universal phenomenon that is both obvious and inevitable, yet poorly understood, and under-researched at the molecular level. Numerous ageing theories have been proposed to explain the progressive and deleterious changes characteristic of ageing. One of the most popular of these is the 'free radical' theory of ageing, which proposes that ageing results from imperfect protection against tissue damage brought about by free radicals. Oxygen free radicals are constantly produced during aerobic metabolism, and certainly provide a universal mechanism for oxidative damage. However, a major obstacle to acceptance of the theory has been the poor record of antioxidants in prolonging the lifespan of small animals. Many other variables, such as genetic factors, temperature, activity and nutrition can affect lifespan, making it a highly complex multi-factorial process.     

Oxygen free radicals and lungs

Some of the metabolites resulting from the monovalent reduction of O₂, superoxide anion and hydroxyl radical, are O₂ radicals, whereas H₂O₂, which is not a radical since having no unpaired electron, is also an active O₂ intermediate. These O₂ metabolites are formed intracellularly as a result of normal metabolism. Their production can increase following exposure to high O₂ concentration, radiations or certain drugs. An increased amount of extracellular O₂ metabolites occurs after activation of certain inflammatory cells or during the course of the hypoxanthine-xanthine oxidase reaction. To counteract this oxidative stress, antioxidant defenses exist, whether enzymatic (superoxide dismutase, glutathione peroxidase, catalase, etc.) or nonenzymatic (GSH, vitamin E and C, etc.). Oxidative injury can result from an imbalance between oxidative stress and the defense mechanisms. The main targets are protein, DNA and lipids. The cellular response of the lung is stereotyped and involves cell injury (especially endothelial c cells and type I pneumocytes), inflammatory reaction and repair processes.     

Oxygen free radicals and lungs

Some of the metabolites resulting from the monovalent reduction of O₂, superoxide anion and hydroxyl radical, are O₂ radicals, whereas H₂O₂, which is not a radical since having no unpaired electron, is also an active O₂ intermediate. These O₂ metabolites are formed intracellularly as a result of normal metabolism. Their production can increase following exposure to high O₂ concentration, radiations or certain drugs. An increased amount of extracellular O₂ metabolites occurs after activation of certain inflammatory cells or during the course of the hypoxanthine-xanthine oxidase reaction. To counteract this oxidative stress, antioxidant defenses exist, whether enzymatic (superoxide dismutase, glutathione peroxidase, catalase, etc.) or nonenzymatic (GSH, vitamin E and C, etc.). Oxidative injury can result from an imbalance between oxidative stress and the defense mechanisms. The main targets are protein, DNA and lipids. The cellular response of the lung is stereotyped and involves cell injury (especially endothelial c cells and type I pneumocytes), inflammatory reaction and repair processes.