肿瘤坏死因子和氧自由基在老龄大鼠多器官衰竭的变化

肿瘤坏死因子和氧自由基在老龄大鼠多器官衰竭的变化＊范利常润英王士雯金道山余颂涛高宇红（解放军总医院老年心脏科老年医学研究所,北京１００８５３）内毒素血症导致的老年多器官功能衰竭（以下简称ＭＯＦ）在临床上极为常见。本文通过对内毒素所致的老龄大鼠ＭＯＦ模...     

肾上腺素对幼龄小鼠胸腺褪黑素受体的调节

应用放射配体结合法检测幼龄小鼠胸腺褪黑素受体（ＭＲ）,并以此为实验模型研究肾上腺素（Ｅ）对胸ＭＲ的影响及作用机制。结果表明,生理浓度的Ｅ即对胸ＭＲ有明显抑制作用,其抑制效应具时间依赖性及剂量依赖性。β－肾上腺素能受体拮抗剂普萘洛尔可逆转引抑制效应,ＣＡＭＰ对ＭＲ也有明显抑制作用,表现Ｅ对ＭＲ的抑制是通过β受体而实现的。这些结果提示,Ｅ在生理情况下即对胸腺ＭＲ有调节作用。     

血管内皮舒张因子在氧自由基所致慢性缺氧大鼠肺内动...

The role of endothelium-derived relaxing factor (EDRF) on the effect of oxygen-derived free radicals (generated by xanthine-xanthine oxidase system) on intrapulmonary arterial in chronic hypoxic rats was studied by a microbioassay method. Intrapulmonary artery rings with intact or denuded endothelium of hypoxic (5,000 m, 10 days) and normoxic rats were prepared for observation of oxygen-derived free radicals induced contraction. It was shown that oxygen-derived free radicals induced contractions of intrapulmonary arterial rings with intact endothelium were obviously augmented in hypoxic rats than in normoxic controls. The augmented responses could be further potentiated by the addition of EDRF inactivator reduced hemoglobin (RHb), but diminished or even abolished by applying superoxide dismutase (Cu-Zn SOD). However, no effect on denuded rings was observed when RHb or SOD was added. It is concluded that chronic hypoxia may attenuate the action of EDRF in the enhancement of the reactivity of intrapulmonary artery to oxygen-derived free radicals.     

胸腺因子D对高密度脂蛋白和低密度脂蛋白的影响

老年人的HDL值为241.3±42.3mg/DL,比中青年低,老年人的LDL值为379.8±124.0mg/DL,比中青年高。胸腺因子D治疗后HDL升高,LDL下降,对乏力、易感冒、寐少、萎糜、纳差、咳痰等症状明显好转。     

脑的氧自由基代谢

中枢神经系统氧自由基代谢的资料 ,是从对衰老及一些精神疾患—主要是老年性痴呆 (Ａｌｚｈｅｉｍｅｒ’ｓＤｉｓ ｅａｓｅ ,ＡＤ)—的研究中获得的。虽然 ,现有资料尚欠全面和系统 ,但不难看出其变化规律有别于脑以外其它脏器及组织的氧自由基代谢。这说明了脑在代谢方面的复杂性和特殊性。且提示 :脑的氧自由基代谢 ,在衰老及ＡＤ的发生发展中的作用是重要的。概括地讲 ,衰老及ＡＤ均表现为渐进性脑功能退化 ,且中枢神经系统的病理变化亦存在着质的相似之处。这说明二者在其发生发展的相关因素中 ,某些是相同的 ,脑的氧自由基代谢紊乱可能…     

血清胸腺因子的固相合成及抗血清的制备

通过Bpoc·Ser(tBu)·Asp·OtBu的β-羧基上树脂和依次用Fmoc·Gly·Gly·OHFmoc·Gln·ONP,Fmoc.Ser(tBu).OH,Fmoc.Lys(Boc)·OH,Fmos·Ala·OH及pGlu·OH伸长,接着氨解和酸解的策略,我们用固相方法合成了血清胸腺因子(FTS,Thymulin),pGlu·Ala·Lys·Ser·Gln·Gly·Gly·Ser·Asn;制备了具有最大生物活性的该因子和Zn~(2+)的复合物,FTS-Zn;用该复合物与牛血清白蛋白(BSA)结合所形成的免疫原免疫家兔,获得了抗FTS-Zn~(++)的抗血清,通过酶联免疫吸附分析法(ELISA)测得其滴度高达1:12800。     

血管内皮舒张因子在氧自由基所致慢性缺氧大鼠肺内动脉收缩中的作用

以黄嘌岭(X)-黄嘌呤氧化酶(XO)系统产生氧自由基,应用微量生物测定法观察慢性缺氧(5000m,10d)对大鼠氧自由基所致肺内动脉收缩的影响及内皮舒张因子(EDRF)在其中的作用。慢性缺氧大鼠有内皮的肺内动脉环对氧自由基的收缩反应较正常环境中的对照动物明显增强,加入EDRF灭活剂还原型血红蛋白(RHb)后更加显著;而加入超氧化物歧化酶(铜锌SOD)后则减弱,甚至消除。反之,不论加入RHb或SOD对氧自由基所致去内皮肺内动脉环的收缩反应均无明显影响。上述结果表明慢性缺氧引起肺内动脉收缩增强与EDRF有密切关系:慢性缺氧可能使EDRF的作用减弱,肺内动脉对氧自由基的反应性增强。表示EDRF及其与氧自由基的关系在慢性缺氧性肺动脉高压的形成中可能具有十分重要的意义。     

Effect of nickel on oxygen free radical metabolism

The effect of nickel on superoxide dismutase activity (SOD), as well as on rate of hydroxydopamine oxidation, was studied in vitro since lipid peroxidation has been implicated in cell damage by nickel, whose toxicity and carcinogenicity are well established. Nickel strongly inhibits SOD activity. The degree of inhibition is directly proportion to the nickel concentration (tested range 0.066 to 0.33 microgram/mL in the reaction mixture); to the substrate concentration (tested range 0.4 x 10 4M to 1.1 x 10 4M 6-hydroxydopamine); and to reaction mixture. Autoxidation of 6-hydroxydopamine was increased by nickel concentrations higher than 15 micrograms/mL. The combination of excessive oxygen free radical production and inhibition of their elimination by inhibition of SOD activity may contribute to the nickel toxicity that has been reported in industrial accidents, as well as to the high incidence of cancer occurring in nickel workers. It may also contribute to many complications in uremic patients, in whom increased serum nickel levels were reported to be in a similar range to those inhibiting SOD.     

Effects of oxygen free radical scavengers on uranium-induced acute renal failure in rats

Study was made to determine whether oxygen free radicals mediate uranium-induced acute renal failure (ARF). Superoxide dismutase (SOD), a superoxide anion scavenger, did not prevent uranium acetate (UA) (5 mg/kg, i.v.)-induced renal injury 48 h after injection. In contrast, dimethylthiourea (DMTU), a hydroxyl radical scavenger, significantly attenuated UA-induced rise in serum creatinine concentration (1.11 ± 0.05 (DMTU) vs. 1.40 ± 0.06 mg/dl (control), p < .05), and tubular necrosis. Dimethyl sulfoxide (DMSO), a hydroxyl radical scavenger, decreased UA-induced tubular damage. UA injection caused no increase in renal cortical malondialdehyde (MDA) content. DMTU and DMSO did not modify intrarenal MDA content. UA administration brought about significant increase in plasma renin activity but not in renal cortical renin content. Treatment with DMTU and DMSO had no effect on plasma renin activity or intrarenal renin content. It follows from these findings that DMTU and DMSO may attenuate UA-induced renal injury. Such a protective effect would not be mediated through modulation of lipid peroxidation or renin activity.     

Effect of stobadine on oxygen free radical generation in stimulated human polymorphonuclear leukocytes

The generation both superoxide and a mixture of reactive oxygen species was recorded in a suspension of human polymorphonuclear leukocytes stimulated with phorbol myristate acetate. While stobadine dose-dependently decreased chemiluminescence, only its highest concentration used reduced significantly superoxide generation. The results suggest that stobadine is a more effective scavenger of free radicals rather than a quencher of superoxide anion.     

Endocrine control of thymic serum factor production in young-adult and old mice

The influence of different endocrinological manipulations on the blood concentration of serum thymic factor (FTS) was studied in young-adult and old mice. Among the experimentally induced endocrinopathies in youth, hypothyroidism and diabetes caused strong reductions of FTS levels, which were restored to normal by the appropriate hormonal substitutive therapy. Removal of adrenals or gonads has no significant effect on FTS level. Old mice, which show undetectable levels of FTS and low levels of thyroxine, can regain the capacity to produce FTS, provided they are treated with thyroxine. The variations of FTS blood levels in the course of endocrinological manipulations were due to a direct or indirect effect exerted on the recipient thymus. Hormonal treatment of thymectomized mice did not induce any FTS-like activity in their sera, nor did hormones interfere in vitro with the bioassay used to test for FTS. These data suggest that the neuroendocrine balance modulates the synthesis and/or the release of FTS from the thymus during the whole life of the organism and that the decline of FTS production with advancing age is largely dependent on age-associated endocrinological imbalances.     

缺氧引起的自由基增殖及其损伤

在缺氧条件下,生物机体内自由基代谢紊乱,其浓度升高,机体抗氧化系统遭到破坏;高浓度自由基通过生物膜脂质过氧化,使生物膜流动性减小,刚性增强,通透性增大,细胞内钙超载,细胞信号传导异常;攻击蛋白质和酶,使其结构破坏,功能丧失。活性降低,导致物质代谢和能量代谢障碍;攻击DNA分子,使其发生突变甚至发生断裂,从而诱发机体病变。     

肠淋巴途径对休克大鼠心肌自由基、炎性介质的影响

目的：观察结扎肠系膜淋巴管对重症失血性休克大鼠不同时期心肌自由基、炎症介质的影响。方法：雄性Wistar大鼠78只,分为假手术组、休克组、结扎组。休克组与结扎组复制重症失血性休克模型,结扎组于休克复苏后行肠系膜淋巴管结扎术。于休克后90min、输液复苏后0h、1h、3h、6h、12h、24h等时间点处死大鼠,制备心肌组织匀浆,检测MDA、SOD、TNFα、IL-6、NO、NOS以及MPO水平,RT—PCR方法测定心肌组织iNOS mRNA表达。结果：休克组大鼠输液复苏后多个时间点心肌匀浆MDA、TNFα、IL-6、MPO、NO、NOS和iNOS mRNA表达均有不同程度的升高,3h-12h持续在较高水平,均显著高于假手术组,心肌匀浆SOD活性显著低于假手术组：结扎组多个时间点心肌匀浆MDA、TNFα、IL-6、MPO、NO、NOS以及iNOS mRNA显著低于休克组相应时间点,SOD活性高于休克组相应时间点。结论：肠系膜淋巴管结扎阻断肠淋巴液回流,可减少心肌PMN扣押、降低TNFα、IL-6的释放、抑制NO生成及iNOS mRNA表达、减少自由基释放与SOD消耗。     

北虫草抗氧自由基和羟自由基作用的研究

基于很多疾病与脂质过氧化有关 ,探讨了利用人工培育的北虫草的抗脂质过氧化作用。结果显示 :人工培育的北虫草子座对 Fenton反应生成的羟自由基具有较强的清除作用 ,且作用明显强于相同剂量的羟自由基特异清除剂甘露醇 (P<0 .0 1 ) ;北虫草对邻苯三酚自氧化体系产生的氧自由基亦具有清除作用 ,与对照组比较 P<0 .0 1 ,但作用弱于相同剂量的抗坏血酸。结果提示 :北虫草具有抗脂质过氧化作用。