小儿原发性肾病综合征血清LPO及全血GSH—PX、Se活性变化及临床意义

本文观察了29例原发性肾病综合征患儿血清 LPO,全血 GSH—PX、Se 活性改变,结果表明:血清 LPO 显著增高,全血 GSH—PX、Se 明显降低。提示该病存在着氧化和抗氧化机制失衡,脂质过氧化反应影响肾病的发生和发展。     

肺癌患者化疗前后血清SOD、LPO、GSH—PX水平的变化及临床意义

目的探讨肺癌患者化疗前后血清SOD、LPO、GSH—PX含量的变化及意义。方法应用放射免疫分析法和生化法对31例肺癌患者进行了化疗前后血清SOD、LPO、GSH—PX含量的检测，并与35名正常人作比较。结果肺癌患者化疗前血清SOD、GSH—PX水平明显低于正常人组（P〈O．01），而LPO则明显高正常人组（P〈0．01），化疗后6个月复发者SOD、LPO、GSH—PX水平持续异常，未复发者SOD、LPO、GSH—PX水平接近正常。结论观察肺癌患者血清SOD、LPO、GSH—PX含量的变化与患者的预后密切相关。     

川芎嗪对老龄小鼠心,肝组织中谷胱甘肽过氧化物酶活化的影响

川芎嗪不同剂量给老龄小鼠灌胃，连续4周．大剂量组可显著升高老龄小鼠心、肝谷光甘肽过氧化物酶（GSH－PX）活性（P＜0.05）。结果提示，川芎嗪通过提高心、肝脏中GSH－PX的活性，能有效地抑制自由基反应，减少自由基对机体的毒害，有抗衰老作用．     

黄连解毒汤对大鼠结肠炎组织损伤的影响

目的研究黄连解毒汤对实验大鼠结肠炎组织损伤的保护作用及其机制。方法用Wirst大鼠建立结肠炎动物模型,灌服用药2周后,取结肠组织评价大鼠结肠黏膜损伤指数(CMDI),检测结肠髓过氧化物酶(MPO)、超氧化物歧化酶(SOD)、谷胱甘肽过氧化物酶(GSH—PX)活性及丙二醛(MDA)的含量。结果不同剂量黄连解毒汤(10、30、50ml／kg体重)灌胃用药后均能不同程度降低模型大鼠结肠黏膜损伤指数(CMDI)和MPO活性、减少MDA含量,提高SOD、GSH—PX活性,且与用药剂量呈一定量效关系。结论黄连解毒汤通过抗脂质过氧化,对大鼠结肠炎结肠损伤进行修复,减轻结肠损伤,抑制结肠炎大鼠炎症反应。     

西洋参茎叶皂甙对急性乙醇中毒大鼠肝损害的影响

本文采用急性乙醇中毒大鼠模型观察了PQS对肝损害的保护作用,结果表明:PQS降低血清丙氨酸转氨酶(ALT)的活性,保护肝脏GSH—PX活性,减少脂质过氧化物(MDA)的生成,西洋参茎叶皂甙对肝损害有保护作用。这种作用部分地与其抗氧化作用有关。     

硒酵母片治疗慢性乙型肝炎临床疗效分析

硒是人体必需的微量元素,适量摄人硒能使体内谷胱甘肽过氧化酶（GSH—PX）活性增加,由于GSH．PX在体内有保护细胞膜完整性、消除自由基、增强体内免疫功能、增强维生素E的抗氧化能力的作用,从而硒能阻止过氧化物对细胞膜、线粒体及溶酶体膜上的脂质产生破坏性的过氧化反应,能保护细胞膜的完整性、稳定性及细胞的正常功能。所以硒也可以称为抗肝坏死保护因子,是阻止肝坏死的因素之一。2006年9月至2008年3月,我们应用硒酵母片治疗60例慢性乙型肝炎患者取得较好的效果。     

头皮针对急性缺血中风自由基的影响

目的观察头皮针对急性缺血中风患者自由基的影响。方法检测头皮针针刺前後患者自由基指标丙二醛（MDA）、超氧化物歧化酶（SOD）、谷胱甘肽过氧化物酶（GSH—PX）和红细胞过氧化氢酶（CAT）的变化。结果头皮针组能降低MDA含量、升高SOD、CAT、GSH—PX含量（P〈0．05）。结论肯定头皮针具有较好抗氧化作用,直接清除自由基,减少脑缺血后自由基对脑细胞的损伤．     

黄芪注射液对慢性肺心病患者血中脂质过氧化物及抗氧化酶活性的影响

目的：探讨黄芪注射液对慢性肺心病患者血中脂质过氧化物及抗氧化酶活性的影响。方法：48例慢性肺心病患者随机分为两组，分别用常规治疗（对照组）及常规治疗加用黄芪注射液（治疗组）治疗14d，观察治疗前后血超氧化岐化酶（SOD）、过氧化脂质（LPO）和谷胱甘肽过氧化物酶（GSH—PX）含量，并与20例健康人（健康对照组）比较。结果：慢性肺心病患者血SOD、LPO含量明显高于健康对照组（P〈0．01），OSH—PX明显低于健康对照组（P〈0．05）；治疗组患者治疗后SOD、LPO明显下降（P〈（1．01），GSH—PX明显上升（P〈0．05）；而对照组患者治疗后SOD，LPO和GSH—PX无明显变化（P〉0．05）。结论：黄芪注射液能明显降低慢性肺心病患者增强的脂质过氧化反应，纠正抗氧化酶的失衡。     

抗氧化药物在肺心病治疗中的意义

本研究在观察慢性肺心病血VitE、脂质过氧化物（LPO）、谷优甘肽过氧化物酶（GSH－PX）、过氧化氨酶（CAT）、超氧化物歧化酶（SOD）、血栓素入（TXA2）、前列腺素I2（PGI2）变化的基础上，并观察了复方丹参、甘糖酯注射液对LPO与抗氧化酶活性的影响。结果表明：VitE含量与GSH－PX、GSH－PX／LPO呈正相关，VitE与LPO、TXB2／6-k-PGF1a呈负相关；复方丹参组治疗后LPO的降低，GSH－PX的增高，甘糖酯组治疗后LPO的降低，CAT的增高，以及两组GSH－PX／LPO增高均较常规组有明显差异。     

盐酸埃他卡林对小鼠脑组织缺氧的保护作用

目的 :研究盐酸埃他卡林 (Ipt)对脑组织缺氧的保护作用。方法 :小鼠给予Ipt 0 .5 ,2 .0 ,8.0mg·kg-13个剂量 (n =12 ,ig) ,连续给药 3wk ,并设生理盐水组和维生素E组作为对照 ,采用断头制备脑缺氧模型。活性采用化学比色法测定脑组织过氧化脂质(MDA)含量、谷胱甘肽过氧化物酶 (GSH PX)和超氧化物歧化酶 (SOD)活性。外周红细胞膜脂流动性以DPH为荧光探针 ,采用荧光偏振法测定。结果 :Ipt0 .5 ,2 .0 ,8.0mg·kg-13个剂量组延长小鼠断头后喘息持续时间 ,增加外周红细胞膜脂流动性 ,降低微粘度 ,且呈现量效关系。相同条件下 ,Ipt对MDA含量 ,GSH PX活性及SOD活性的影响不明显。结论 :Ipt对脑组织缺氧有显著保护作用 ,其作用可能与其改变血液流变学特性有关。     

阿霉素对大鼠全血和心肌超氧化物歧化酶活性的影响

本文研究了阿霉素对大鼠全血和心肌超氧化物歧化酶(SOD)活性的影响。给大鼠腹腔注射阿霉素4.5mg/kg,每日一次,共四次,可引起大鼠血和心肌SOD活性明显降低。给予阿霉素前一天腹腔注射VitE豆油溶液2500mg/kgl次,可使SOD活性得到恢复。     

硫普罗宁对阿霉素心脏毒性的保护作用及机制

目的：研究硫普罗宁（MPG）对阿霉素（ADM）心脏毒性的保护作用及机制。方法：建立ADM损伤大鼠心脏模型,灌胃给予MPG,检测血清肌钙蛋白工（cTnⅠ）、肌酸激酶同工酶（CK—MB）及脑钠肽（BNP）、心肌组织超氧化物歧化酶（SOD）活力,丙二醛（MDA）、一氧化氮（NO）含量及一氧化氮合酶（NOS）的活性,并观察心肌组织病理改变。结果：与ADM大鼠心脏模型组相比,MPG干预ADM处理后大鼠的血清cTnI、CK．MB及BNP显著降低（P〈0．05或P〈0．01）,心肌组织SOD活力显著增高,MDA、NO含量,总NOS活力及iNOS活力显著降低（P均〈0．01）,心肌组织病理积分显著下降（P〈0．05）。结论：MPG对ADM心脏毒性具有较好的保护作用;MPG可能通过恢复心肌组织SOD的活力、抑制iNOS活性使心肌组织NO产生减少,从而减轻ADM所致大鼠心肌组织的氧化损伤。     

硫普罗宁对阿霉素心脏毒性的保护作用及机制

目的：研究硫普罗宁（MPG）对阿霉素（ADM）心脏毒性的保护作用及机制。方法：建立ADM损伤大鼠心脏模型,灌胃给予MPG,检测血清肌钙蛋白Ⅰ（cTnⅠ）、肌酸激酶同工酶（CK-MB）及脑钠肽（BNP）、心肌组织超氧化物歧化酶（SOD）活力,丙二醛（MDA）、一氧化氮（NO）含量及一氧化氮合酶（NOS）的活性,并观察心肌组织病理改变。结果：与ADM大鼠心脏模型组相比,MPG干预ADM处理后大鼠的血清cTnⅠ、CK—MB及BNP显著降低（P〈0．05或P〈0．01）,心肌组织SOD活力显著增高,MDA、NO含量,总NOS活力及iNOS活力显著降低（P均〈0．01）,心肌组织病理积分显著下降（P〈0．05）。结论：MPG对ADM心脏毒性具有较好的保护作用;MPG可能通过恢复心肌组织SOD的活力、抑制iNOS活性使心肌组织NO产生减少,从而减轻ADM所致大鼠心肌组织的氧化损伤。     

Late effects of adriamycin single dose on fetal rat kidney-ultrastructural assessment

The purpose of the study was ultrastructural evaluation of long-lasting activity of an antibiotic from anthracycline group-adriamycin (ADR), on fetal kidneys from rat females which 4 weeks before fertilization were given a single dose of adriamycin intraperitoneally. The results showed the damage of glomerular filtration barrier (fusion of podocytes' foot processes) and degenerative lesions in tubular epithelial cells (EC). Those changes were described in literature in the case of adriamycin induced nephrotic syndrome in adult rats. If those lesions are due to increased glomerular permeability for proteins or cytotoxic activity of adriamycin can be decided after further biochemical tests of fetal urine and blood.     

Activity profile of calpains I and II in chronically infarcted rat myocardium--influence of the calpain inhibitor CAL 9961

1. The calpains have been proposed to be activated following cardiac ischaemia and to contribute to myocyte damage after myocardial infarction (MI). In this study, the activity of calpains I and II in the infarcted and non-infarcted rat myocardium and the action of the selective calpain inhibitor, CAL 9961, has been investigated. 2. MI was induced by permanent ligation of the left coronary artery. One, 3, 7 and 14 days post MI, the enzymes calpain I and II were separated from homogenates of the interventricular septum (IS) and left ventricular free wall (LVFW) by chromatography on DEAE-Sepharose. The activity of the calpains was measured in sham-operated and MI animals chronically treated with placebo or CAL 9961 (15 mg kg(-1) d(-1) s.c.) in a synthetic substrate assay. Treatment was started 3 days before MI induction. 3. Calpain I activity reached highest values in IS 14 days post MI, whereas maximum activity of calpain II was measured in LVFW 3 days post MI. In experiments in vitro, CAL 9961 completely inhibited both calpains. In vivo, chronic treatment of MI animals with CAL 9961 partially prevented the increase in calpain I activity in IS and reduced calpain II activity in LVFW to sham levels. 4. Our findings demonstrate that calpains I and II are activated after MI, however, both enzymes differ in their regional and temporal activation within the infarcted myocardium. Chronic inhibition of these enzymes with CAL 9961 might limit the calpain-induced myocardial damage and preserve cardiac structural integrity post MI.     

Lipid Peroxidation Induced by Adriamycin in Linolenic Acid-Loaded Cultured Hepatocytes

Abstract: Addition of more than 10 μM of adriamycin to cultured rat hepatocytes loaded with α-linolenic acid (linolenic acid-loaded hepatocytes) caused marked lipid peroxidation as measured by an accumulation of malondialdehyde during a 9 hr incubation. After addition of 50 μM of adriamycin to linolenic acid-loaded hepatocytes, malondialdehyde accumulation significantly increased at 3 hr, followed by cellular reduced glutathione decrease and lactate dehydrogenase leakage after 6 hr. Inhibition of adriamycin-induced lipid peroxidation by addition of N, N′-diphenyl-p-phenylenediamine or α-tocopherol, both lipid radical scavengers, or deferoxamine, which is a Fe ion chelator, prevented both glutathione decrease and lactate dehydrogenase leakage, indicating that lipid peroxidation caused cellular damage to linolenic acid-loaded hepatocytes exposed to adriamycin. The effect of SKF 525-A, which is a cytochrome P450 inhibitor, on adriamycin-induced lipid peroxidation and on 7-ethoxycoumarin O-deethylase activity was determined by 6 hr incubation of linolenic acid-loaded cells. Addition of SKF 525–A suppressed adriamycin-induced lipid peroxidation comparably with its 7-ethoxycoumarin 0-deethylase inhibitory activity. These results suggest that cytochrome P450 contributes to the one-electron bioreduction of adriamycin into its semiquinone radical in rat hepatocytes.     

The effects of alpha-tocopherol on the toxicity, disposition, and metabolism of adriamycin in mice.

Fourteen days after adriamycin treatment, 15 mg/kg ip, there was greater than 50% mortality in CDF₁ mice pretreated with either olive oil or saline ip, but only 5% mortality in animals pretreated with a single dose of α-tocopherol. However, 60 days after adriamycin, mortality was 80±5% in all three groups. A single dose of α-tocopherol alone caused no deaths. Blood concentrations of [¹⁴C]adriamycin-derived radioactivity in mice pretreated with α-tocopherol of olive oil were significantly higher than those of saline controls between 3 and 15 min after injection. At 30 and 60 min blood concentrations of radioactivity did not differ in the three groups. Sixty minutes after adriamycin administration, concentrations of radioactivity in heart, kidney, muscle, and lung were significantly higher in the α-tocopherol and olive oil groups than in the saline controls. No differences in the metabolic profile of adriamycin were found in heart or liver, but renal concentration of adriamycin and several metabolites were higher in both the α-tocopherol and olive oil groups. In general, α-tocopherol pretreatment had only slight effect on the metabolism of adriamycin in vivo. Thus, the time-dependent efficacy of α-tocopherol in ameliorating the lethal toxicity of adriamycin in mice does not appear to result from acute changes in the distribution or metabolism of adriamycin. It appears that the effect of α-tocopherol is to delay rather than prevent the lethal toxicity of adriamycin.     

Unique presynaptic alpha 2-receptor selectivity and specificity of the antihypertensive agent moxonidine

The characteristics of the alpha-receptor activating property of the new antihypertensive agent moxonidine (4-chloro-N-(4, 5-dihydro-1H-imidazol-2-yl)-6-methyl-2-methyl-5-pyrimidinamine, BDF 5895) was studied using peripheral vasculature and brain membranes of various animals. Moxonidine exerted a full agonist effect in elevating diastolic blood pressure in the pithed rat. Activation of postsynaptic alpha 1- and alpha 2-receptors contribute to the vasoconstrictory effect in rats. In the vasculature of the rabbit, moxonidine was a full agonist at presynaptic alpha 2-receptors in inhibiting transmitter release induced by electrical stimulation of pulmonary artery strips. At postsynaptic sites, exogenously applied moxonidine was a full agonist at alpha 1-receptors in the isolated aorta, pulmonary artery and vena cava of the rabbit. Selectivity for alpha 2-receptors in the pulmonary artery was 106-fold. In rat brain membranes, moxonidine showed 288-fold greater selectivity for alpha 2-receptors, when the displacement of [3H]-rauwolscine was compared with the displacement of [3H]-prazosin. On the whole, clonidine exhibited greater potency than moxonidine on both alpha-receptor subtypes, but moxonidine consistently showed greater alpha 2-receptor selectivity than clonidine. In the guinea pig myocardium, moxonidine caused neither bradycardia nor tachycardia in the isolated right atrium and produced a negligible positive inotropic effect at 100 mumol/l in the isolated papillary muscle.     

Effects of monoamine uptake inhibitors on extracellular and platelet 5-hydroxytryptamine in rat blood: different effects of clomipramine and fluoxetine.

1. The concentration of 5-hydroxytryptamine (5-HT) in rat platelet-free plasma increased significantly 30 min after a single i.p. injection (10 mg kg-1) of each of six inhibitors of the high-affinity 5-HT uptake (fluvoxamine, fluoxetine, alaproclate, paroxetine, sertraline and clomipramine). The increases ranged from 226% to 776% of control values. In contrast, imipramine, desipramine and femoxetine had no significant effect. The increase elicited by paroxetine was dependent on the dose (1, 5 and 10 mg kg-1) and returned to control values after 4 h. That observed after clomipramine was also transient and paralleled the plasma concentration of the drug (Spearman-rank correlation r = 0.43). 2. In vivo, the rat pulmonary vascular endothelium removed trace amounts (8.8 nmol in a bolus) of intravenously injected [14C]-5-HT. Paroxetine pretreatment (10 mg kg-1, 30 min before-hand) reduced this uptake by 73%. 3. Repeated fluoxetine treatments reduced rat whole blood 5-HT concentration (ca. -60% after daily 2 x 5 mg kg-1, i.p. during 14 days). However, plasma (extracellular) 5-HT was not increased. 4. Various repeated treatments with clomipramine (i.p. injections or osmotic minipumps, up to 30 mg kg-1 day-1), failed to decrease rat whole blood 5-HT concentrations. Platelet-free plasma 5-HT was also unchanged, even after treatments yielding plasma clomipramine levels 2.7 times higher than those that increased it acutely. 5. These results indicate that the extracellular pool of 5-HT in rat blood (measured in the platelet-free plasma) is physiologically under the control of high-affinity 5-HT uptake systems.(ABSTRACT TRUNCATED AT 250 WORDS)     

Effect of Zileuton (A-64077) on the 5-lipoxygenase activity of human whole blood ex vivo.

The potency and reversibility of a new orally active 5-lipoxygenase (5-LO) inhibitor were evaluated in human volunteers. Zileuton (A-64077) 600 mg q.i.d. was administered to volunteers for 14 days in a phase I study, and blood samples were withdrawn, stimulated with ionophore A23187 and LTB4 levels were determined using both reverse phase high performance liquid chromatography (RP-HPLC) and radioimmunoassay (RIA). The drug significantly inhibited (above 70%) LTB4 biosynthesis in whole blood stimulated with A-23187 throughout the 14 days. The activity of 5-LO was also measured one week after stopping the medication and was returned to control levels. Measurement of LTB4 levels using either RP-HPLC or RIA gave similar percentage of inhibition although RIA appeared to underestimate by half the absolute amounts of LTB4 in the blood samples. These results show that Zileuton is a highly active and reversible 5-LO inhibitor in human.