黄芩甙对大鼠心肌缺血再灌注所致脂质过氧化损伤的保护作用

目的：研究黄芩甙（baicalin,Bai)对大鼠心肌缺血再灌注所致脂质过氧化损伤的保护作用。方法：采用结扎在体大鼠冠状动脉左前降支造成心肌缺血30min,随后恢复血流行再灌注120min,复制心肌缺血再灌注损伤模型。结果：Bai能不同程度地降低缺血再灌注所引起心肌组织脂质过氧化物丙二醛（MDA）含量升高,提高超氧化物歧化酶（SOD）活性,保护Na^ -K^ -ATP酶活力,降低血清肌酸激酶（CK）和乳酸脱氢酶（LDH）水平。结论：Bai可通过保护脑组织抗氧化酶的活性,抑制脂质过氧化反应,减轻自由基对心肌组织的损害,对缺血再灌注心肌产生保护作用。     

去氢表雄酮对培养的人脐静脉血管内皮细胞抗氧化能力的影响

为观察去氢表雄酮（DHEA）对人脐静脉内皮细胞（HUVEC）抗氧化能力的影响,分别检测经不同浓度DHEA（1μmol/L,5μmol/L,50μmol/L）处理的HUVEC培养液中过氧化脂质代谢产物丙二醛（MDA）及超氧化物歧化酶（SOD）的含量。结果显示：经肿瘤坏死因子α（TNF-α）干预后,培养液中SOD含量下降,MDA升高（P＜0．05）;加用DHEA后培养液中SOD含量回升,MDA下降,高浓度组作用最明显（P＜0．01）。结果表明,DHEA可增加内皮细胞的抗氧化能力,可能为其抗动脉粥样硬化的机制之一。     

Free radical-induced elevation of ornithine decarboxylase activity in developing rat brain slices

Objective. In developing brain, we have previously shown both in vivo [L.D. Longo, S. Packianathan, J.A. McQueary, R.B. Stagg, C.V. Byus and C.D. Cain, Acute hypoxia increases ornithine decarboxylase activity and polyamine concentrations in fetal rat brain, Proc. Natl. Acad. Sci. USA, Vol. 90 (1993) 692–696] and in vitro [S. Packianathan, C.D. Cain, B.H. Liwnicz and L.D. Longo, Ornithine decarboxylase activity in vitro in response to acute hypoxia: a novel use of newborn rat brain slices, Brain Res., Vol. 688 (1995) 61–71] that acute hypoxia is associated with a significant increase in ornithine decarboxylase (ODC) activity and polyamine concentrations. We tested the hypothesis that oxygen free radicals induce an increase in ODC activity similar to that of hypoxia and that both this and the hypoxia-induced response are inhibited by free radical scavengers. Materials and methods. Slices of cerebrum, 300–500 μm thick, were made from P3 newborn Sprague-Dawley rat pups and equilibrated for 1 h in artificial cerebrospinal fluid continuously bubbled with 95% O₂/5% CO₂. Free radical-induced ODC activity response was measured beginning after a 1-h recovery period. Experiments were performed on slices treated with 5×10⁻⁷ M xanthine (X)+10 mU/ml xanthine oxidase (XO), with or without the free radical scavengers superoxide dismutase (SOD; 100 U/ml), catalase (CAT; 700 U/ml) or glutathione peroxidase (GPX; 3 U/ml). We also quantified slice malonaldehyde concentrations in response to hypoxia (21% O₂/5% CO₂/74% N₂). Results. Under control conditions, ODC activity was stable during the 2-h post-recovery period. In response to X/XO treatment, ODC activity increased 2.3-fold at 1.5 h post-recovery. In examining ODC activity as a function of xanthine dose, we noted that ODC activity increased in response to 2.5×10⁻⁷ M xanthine; however, it decreased in response to 7.5×10⁻⁷ M or higher concentrations. Free radical-induced ODC activity was significantly decreased by addition of the free radical scavengers, SOD, CAT or GPX. In addition, the hypoxic-induced increases in ODC activity and malonaldehyde concentration was also eliminated by the addition of SOD with CAT. Conclusions. (1) Oxygen free radicals, particularly hydroxyl radical (OH^.), appear to trigger an induction of ODC activity in newborn rat cerebrum slices. (2) Oxygen free radicals also appear to mediate the hypoxic-induced increase in ODC activity. (3) Any consequent increase in polyamine synthesis may have profound effects on neurogenesis and neurodifferentiation in the developing brain.     

Oxidative stress markers and C-reactive protein in end-stage renal failure patients on dialysis

OBJECTIVE: The inflammatory status is a well-documented factor influencing the development of oxidative stress in dialysis patients. This study intends to evaluate the inflammatory activity and the plasma levels of total antioxidant capacity (TAC) and lipid peroxidation products in patients on peritoneal dialysis (PD), by comparison with hemodialysis (HD) patients. PATIENTS AND METHODS: Plasma concentration of TAC, lipid peroxidation products and C-reactive protein (CRP) were measured in 24 patients on PD, 32 HD patients (pre and post treatment) and 16 normal controls (NC). RESULTS: All patients had higher levels of TAC and lipid peroxidation products than NC (p < 0.001). Patients on PD, had similar levels to patients before HD but significantly higher (p < 0.001) than those post HD. The CRP concentration was higher in HD than in PD patients (p < 0.05). The percentage of patients with CRP > 10 mg/l was 48% in HD patients and 21% in PD patients. No correlation was observed between CRP and TAC nor CRP and MDA levels. CONCLUSIONS: We conclude that although PD and HD patients show an equal susceptibility in oxidative stress, CRP levels are higher in HD patients and this is indicative of a higher degree of inflammatory activity in these patients.     

职业性铝接触对红细胞膜Na—K—ATP酶活性的影响

为探讨铝的毒作用机制．本研究选择某铝厂铝作业工人72名作为研究对象，以同一地区非铝作业工人41名作为对照人群，观察铝对职业人群红细胞膜Na-K－ATP酶活性的影响。结果显示，各年龄段铝作业工人的尿铝含量均明显高于对照组；丙二醛（MDA）含量无显著性差异；Na－K－ATP酶活性铝接触组与对照组之间有明显差异，以35～44岁年龄段铝作业工人为最高，并与同年龄段对照工人存在显著性差异。长期职业性铝接触可以引起红细胞膜Na－K－ATP酶活性升高，这一结果可能是由于铝的直接作用，而与机体脂质过氧化作用无关．     

三羟异黄酮对血管性痴呆大鼠学习记忆及脑内氧化损伤的影响

目的：研究植物雌激素三羟异黄酮（GST）对血管性痴呆模型大鼠学习记忆的影响及其作用机制.方法：采用双侧颈总动脉结扎再灌注合并硝普钠降压法制作大鼠血管性痴呆模型,所有大鼠被分为模型对照组（O组）、假手术对照组（C 组）、三羟异黄酮组（GST组）和苯甲雌二醇组（BE2组）4组,采用大鼠跳台法、Morris水迷宫法检测各组大鼠学习记忆能力,并测定大鼠脑组织中超氧化物歧化酶（SOD）、丙二醛（MDA）、谷胱甘肽过氧物酶（GSHPx）的含量.结果：GST组与O组相比,GST明显提高模型大鼠学习记忆能力,降低MDA,提高SOD、GSHPx的含量.结论：GST可能通过抗氧化损伤、清除自由基的作用,从而改善模型大鼠的学习记忆能力.     

香烟或烟嘴内植物色素对吸烟大小鼠的抗氧化损伤作用

目的　研究植物色素 (PP)分别加入香烟和烟嘴内对吸烟大、小鼠的抗氧化损伤作用。方法　抗氧化试验方法。雌性小鼠 4 0只 ,雄性大鼠 32只 ,分别随机分为 4组。 2个对照组 (阴性组和吸烟对照组 ) ,2个实验组 (烟内组和烟嘴组 )。观察PP对吸烟大小鼠血浆超氧化物歧化酶 (P SOD)、红细胞SOD(E SOD)和肝细胞丙二醛 (L MDA)的影响。数据经方差分析。结果　 2个试验组小鼠P SOD升高 ,烟嘴组E SOD也升高 ,上述升高与吸烟对照组比较差异非常显著(P <0 .0 1) ,与阴性组比较无显著差异 (P >0 .0 5 ) ;2个试验组小鼠L MDA降低 ,烟内组与吸烟对照组比较差异非常显著(P <0 .0 1) ,与阴性组比较无显著差异 (P >0 .0 5 )。 2个试验组大鼠P SOD、E SOD升高与吸烟对照组比较差异显著 (P<0 .0 5 ) ,与阴性组比较无显著差异 (P >0 .0 5 ) ;烟内组和烟嘴组大鼠L MDA降低与吸烟组比较差异显著和极显著 (P <0 .0 5、P <0 .0 1) ,与阴性组比较无显著差异 (P >0 .0 5 )。结论　PP加入香烟或烟嘴内 ,可显著的减轻吸烟大、小鼠的氧化损伤作用。     

一氧化氮肝脏保护作用与氧自由基的关系

目的探讨内源性一氧化氮(NO)对大鼠肝缺血再灌注损伤的作用及其与脂质过氧化的关系;方法以缺血再灌注制成大鼠模型,以工具药L-精氨酸(L-arg)为外源性NO的激动剂,观察内源性NO对肝脏损伤程度和脂质过氧化终产物丙二醛(MDA)含量的影响;结果缺血再灌注可造成肝组织损伤,MDA含量增加,内源性NO水平降低,与对照组比较(P＜0.01).以L-arg激动内源性NO,可明显减轻肝组织损伤程度,同时MDA含量降低,NO水平升高,与IR组比较(P＜O.05);结论内源性NO具有肝脏保护作用,其保护机制可能与抗氧自由基有关.     

慢性脑低灌注对大鼠皮层核因子E2相关因子2表达的影响

目的 研究慢性脑低灌注大鼠皮层核因子E2相关因子2(Nrf2)的表达.方法 用随机数字表法将大鼠分为双血管结扎术(2VO)-3周组、2VO-8周组和假手术组,2VO术式制备慢性脑低灌注大鼠模型并在相应时间点取材,采用免疫组化染色、实时定量PCR方法检测大鼠皮层Nrf2的表达,用硫代巴比妥酸法测定丙二醛(MDA)含量.结果 免疫组化染色结果显示,与假手术组(38.01%±4.51%)相比,2VO-3周组(50.18%±14.22%)、2VO-8周组(23.15%±7.42%)大鼠皮层Nrf2阳性细胞比例差异均无统计学意义(P＞0.05);与2VO-3周组相比,2VO-8周组大鼠皮层Nrf2阳性细胞比例明显降低,比较差异有统计学意义(P＜0.05).实时定量PCR结果提示,2VO-8周组大鼠皮层Nrf2 mRNA的表达(相对扩增倍数)较2VO-3周组降低,但差异无统计学意义(P＞0.05).生化检测发现,与假手术组[(3.894±0.512)nmol/mg]相比,2VO-8周组大鼠皮层MDA含量[(6.855±1.351)nmol/mg]明显升高,比较差异有统计学意义(P＜0.05).结论 慢性脑低灌注大鼠皮层MDA含量随时间延长而不断增加,除3周时蛋白表达上调外,Nrf2蛋白与mRNA水平均有不同程度减低,提示慢性脑低灌注状态时氧化性损伤持续加重,这可能与内源性抗氧化系统受到抑制有关.

Abstract：

Objective To examine the effect of chronic cerebral hypoperfusion (CCH) on the expression of nuclear factor E2-related factor 2 (Nrf2) in rat cortex. Methods Rats were randomly divided into 2 operated groups and a sham-operated group; rat models of chronic cerebral hypoperfusion in the 2 operated groups were established by occlusion of bilateral common carotid arteries (2VO) for 3 and 8 weeks, respectively. The RNA and protein contents of Nrf2 in the cortex were detected by immunohistochemistry and real-time quantitative PCR, respectively, and the content of malonaldehyde (MDA) was measured by thiobarbituric acid-reactive substance assay. Results A significantly lower percentage of Nrf2-positive cells in the cortex of 2VO-8w group (23.15%±7.42%) was noted as compared with that in the 2VO-3w group (50.18%±14.22%) (P＜0.05); no significant differences on the percentage of Nrf2-positive cells were noted between the sham-operated group (38.01%±4.51%) and the 2 operated groups (P＞0.05). Though the RNA content of Nrf2 in the cortex of 2VO-8w group (0.993 ±0.492)decreased as compared with that in the 2VO-3w group (1.536±0.493)(P＞0.05), no statistical difference was noted between the sham-operated group (1.690± 1.195) and both the 2VO-3w group and the 2VO-8w group (P＞0.05). And the content of MDA in the 2VO-8w group ([6.855±1.351] nmol/mg) was significantly increased as compared with that in the sham-operated group ([3.894±0.512] nmol/mg) (P＜0.05). Conclusion The content of MDA keeps increasing. Additionally, except the protein expression up-regulates 3 weeks after occlusion, the RNA and protein expressions of Nrf2 in rat cortex are down-regulated with the process of CCH, suggesting that oxidative damage become much severe with theprocess of CCH, which may be partly attributed to the dysfunction of endogenous antioxidative mechanisms.