延衰合剂对D-半乳糖衰老模型小鼠学习记忆及抗氧化能力的影响(英文)

为观察延衰合剂(Yanshuai mixture,YSM)的延缓衰老作用,采用D-半乳糖连续颈背部皮下注射诱导亚急性衰老小鼠模型,造模同时给予YSM低、中、高剂量灌胃,连续10周。观察小鼠衰老征象,Moriss水迷宫检测学习记忆功能,测定血清及脑组织中总抗氧化能力(T-AOC)、超氧化物歧化酶(SOD)、丙二醛(MDA)。结果显示,与模型组比较,YSM各剂量组均能使小鼠逃避潜伏期明显缩短,原平台象限游泳时间明显延长(P<0.05);YSM高剂量组T-AOC、SOD活性显著升高(P<0.01),MDA水平显著下降(P<0.01)。表明YSM可明显改善衰老小鼠学习记忆功能,提高抗氧化能力,从而可能具有较好的延缓衰老的作用。     

小檗碱对动脉粥样硬化性损伤的保护作用

目的:探讨小檗碱对动脉粥样硬化损伤的保护作用。方法:将56只大鼠,随机分为对照组(C),高脂饮食假手术组(HD),肾动脉狭窄组(RAS),肾动脉狭窄高脂饮食组(HD+RAS)。C及RAS组给予正常饮食,HD及HD+RAS组给予高脂饮食,RAS及HD+RAS组采用固定内径银夹夹左肾动脉。饲养12周,每组处死6只进行检测,剩余除C外每日灌胃小檗碱(150mg/kg),C予以等量生理盐水灌服,持续4周,四周后处死进行相同检测,用药前后结果进行对比评价小檗碱功能。结果:与C相比,HD,RAS,HD+RAS组肌酐显著升高(P<0.05),HD及HD+RAS组胆固醇明显升高(P<0.05),超氧化物歧化酶(SOD)在HD,RAS及HD+RAS组显著降低(P<0.05),丙二醛(MDA)在HD,RAS及HD+RAS组显著增高(P<0.05),血管内皮生长因子VEGF在HC,RAS及HD+RAS组表达量升高。给予小檗碱灌胃处理后,检测指标各组间无统计学差异(P>0.05)。结论:小檗碱对动脉粥样硬化性损伤具有良好的保护作用。     

The effects of isoniazid on hippocampal NMDA receptors: Protective role of Erdosteine

Isoniazid (INH) has neurotoxic effects such as seizure, poor concentration, subtle reduction in memory, anxiety, depression and psychosis. INH-induced toxic effects are thought to be through increased oxidative stress, and these effects have been shown to be prevented by antioxidant therapies in various organs. Increased oxidative stress may be playing a role in these neurotoxic effects. N-methyl D-aspartat receptors (NMDA) are a member of the ionotropic group of glutamate receptors. These receptors are involved in a wide variety of processes in the central nervous system including synaptogenesis, synaptic plasticity, memory and learning. Erdosteine is a potent antioxidant and mucolytic agent. We aimed to investigate adverse effects of INH on rat hippocampal NMDAR receptors, and to elucidate whether erdosteine prevents possible adverse effects of INH. In the present study, compared to control group, NMDAR2A (NR2A) receptors were significantly decreased and malondialdehyde (MDA), end product of lipid peroxidation, production was significantly increased in INH-treated group. On the other hand, administration of erdosteine to INH-treated group significantly increased NR2A receptors and decreased MDA production. In conclusion, decreasing NR2A receptors in hippocampus and increasing lipid peroxidation correlates with the degree of oxidative effects of INH and erdosteine protects above effect of INH on NR2A receptors and membrane damage due to lipid peroxidation by its antioxidant properties.     

The use of whole genome amplification in the study of human disease

The availability of large amounts of genomic DNA is of critical importance for many of the molecular biology assays used in the analysis of human disease. However, since the amount of patient tissue available is often limited and as particular foci of interest may consist of only a few hundred cells, the yield of DNA is often insufficient for extensive analysis. To address this problem, several whole genome amplification (WGA) methodologies have been developed. Initial WGA approaches were based on the polymerase chain reaction (PCR). However, recent reports have described the use of non-PCR-based linear amplification protocols for WGA. Using these methods, it is possible to generate microgram quantities of DNA starting with as little as 1mg of genomic DNA. This review will provide an overview of WGA approaches and summarize some of the uses for amplified DNA in various high-throughput genetic applications.     

MDA‐7/IL‐24 regulates proliferation,invasion and tumor cell radiosensitivity: A new cancer therapy?

The novel cytokine MDA-7/IL-24 was identified by subtractive hybridization in the mid-1990s as a cytokine whose expression increased during the induction of terminal differentiation, and that was either not expressed or was present at low levels in tumor cells compared to non-transformed cells. Multiple studies from several laboratories have subsequently demonstrated that expression of IL-24 in tumor cells, but not in non-transformed cells, causes their growth arrest and ultimately cell death. In addition, IL-24 has been noted to be a radiosensitizing cytokine, which in part is due to the generation of reactive oxygen species (ROS) and causing endoplasmic reticulum stress. Recent publications of Phase I trial data have shown that a recombinant adenovirus to express MDA-7/IL-24 (Ad.mda-7 (INGN 241)) was safe and had tumoricidal effects in patients, which argues that IL-24 may have therapeutic value. This review describes what is known about the impact of IL-24 on tumor cell biology in addition to approaches that may enhance the toxicity of this novel cytokine.     

Effects of exogenous metallothionein on acute cadmium toxicity in rats

The present study was carried out to evaluate the effect of exogenously administered metallothionein (MT) to rats exposed to high cadmium levels. A total of 72 rats were used in the study. The animals were divided into three groups: controls, Cd administered, and Cd+MT. Cadmium was administered by subcutaneous injection of cadmium(II) chloride at a dose of 3.5 mg/kg for 7 d. In addition to CdCl₂, 30 μmol/kg MT was administered to the second group of rats (group II). Control rats received 0.5 mL physiologic serum via subcutaneous injection. Eight rats from each group were sacrificed on the 1st, 3rd, 5th, and 7th day after administration of the compounds. Liver, kidney, and blood samples were harvested. Levels of malondialdehyde (MDA), glutathione peroxidase (GSH-Px), serum ALT, AST, BUN, ALP, creatinine, and urea were measured. MDA levels in group I were observed to increase starting from d 1 compared to group II (p<0.05). Although MDA levels in group II were higher than controls (p<0.05), they were lower, especially in liver and blood, compared to group II. Erythrocyte GSH-Px activity levels were determined to decrease starting from d 1 in both groups (p<0.05). Decreases in GSH-Px activity levels in group II were less than group I. Serum creatinine levels in both groups were increased significantly compared to controls (p<0.05); the increase in group I was higher than group II. Serum ALT, AST, and ALP levels in group I increased to very high levels compared to controls, whereas increases in group II were at moderate levels (p<0.05). Although serum BUN levels were determined to be reduced, there was no significant change among the groups. Serum urea levels in both groups were higher than controls. Based on our results, it is possible to postulate that exogenous MT can act as antioxidant against Cd toxicity and lipid peroxidation.     

Aluminum mediates compositional alterations of polar lipid classes in maize seedlings

Changes in lipid composition were investigated on maize roots and shoots under aluminum stress. After 4d exposure to 100 microM Al, root growth was inhibited while shoot growth was not affected. In roots, the decrease of the DBI (double bond index) of total fatty acids may signal a decrease in membrane fluidity. The total lipids (TL) decreased by 49%, but phospholipids (PL), phosphatidylcholine (PC) and phosphatidylinositol (PI) increased to approximately 3-fold. The MGDG increased to 2-fold but no significant change was found in the DGDG. The steryl lipids (SL) increased by 69%. The SL/PL ratio decreased from 2.64 to 1.52 and the MGDG/DGDG ratio increased from 0.45 to 1.06 in roots of Al-stressed plants. Al leads to oxidative stress in roots of treated plants as indicated by the increase of malondialdehyde (MDA) concentrations. In shoots, changes in fatty acid composition were associated with an increase of the DBI in all lipid classes except that of the DGDG decreased. The PG was the lipid class which shows the large variation of fatty acid composition. No significant changes were found either for TL, PL, SL or MDA concentrations in shoots of Al-treated plants. While PE levels did not show significant change, PI and PG increased and PC decreased. However, the Al caused 87% decrease in the GL levels. The MGDG and DGDG decreased to 19- and 8-fold, respectively. The deleterious effects of Al on polar lipids could be caused by a direct intervention of Al on plasma membrane and/or alteration of cell metabolism.     

Possible mechanisms underlying copper-induced damage in biological membranes leading to cellular toxicity

It is generally accepted that copper toxicity is a consequence of the generation of reactive oxygen species (ROS) by copper ions via Fenton or Haber-Weiss reactions. Copper ions display high affinity for thiol and amino groups occurring in proteins. Thus, specialized proteins containing clusters of these groups transport and store copper ions, hampering their potential toxicity. This mechanism, however, may be overwhelmed under copper overloading conditions, in which copper ions may bind to thiol groups occurring in proteins non-related to copper metabolism. In this study, we propose that indiscriminate copper binding may lead to damaging consequences to protein structure, modifying their biological functions. Therefore, we treated liver subcellular membrane fractions, including microsomes, with Cu²⁺ ions either alone or in the presence of ascorbate (Cu²⁺/ascorbate); we then assayed both copper-binding to membranes, and microsomal cytochrome P450 oxidative system and GSH-transferase activities. All assayed sub-cellular membrane fractions treated with Cu²⁺ alone displayed Cu²⁺-binding, which was significantly increased in the presence of Zn²⁺, Hg²⁺, Cd²⁺, Ag⁺¹ and As³⁺. Treatment of microsomes with Cu²⁺ in the μM range decreased the microsomal thiol content; in the presence of ascorbate, Cu²⁺ added in the nM concentrations range induced a significant microsomal lipoperoxidation; noteworthy, increasing Cu²⁺ concentration to ≥50 μM led to non-detectable lipoperoxidation levels. On the other hand, μM Cu²⁺ led to the inhibition of the enzymatic activities tested to the same extent in either presence or absence of ascorbate. We discuss the possible significance of indiscriminate copper binding to thiol proteins as a possible mechanism underlying copper-induced toxicity.     

(NH4)2SO4对瓜尔豆幼苗在不同光照下耐冷性的影响

通过温室穴盘育苗试验,研究叶面喷施(NH4)2SO4对低温胁迫12 h后不同光通量密度(PFD)条件下,瓜尔豆幼苗在常温培养过程中幼苗生存及叶片SOD活性、POD活性和MDA含量的影响。结果表明:低温处理一夜后,在温室自然光照(强光)下进行常温恢复时,瓜尔豆叶片中SOD和POD活性始终显著低于对照,MDA含量显著高于对照,幼苗死亡率显著高于对照;在90μmol.m-2.s-1弱光下恢复2~4 d后,叶片中保护酶活性显著高于对照,MDA含量保持较低水平,幼苗均正常生长。叶面喷施(NH4)2SO4能显著提高低温处理后的植株叶片抗氧化酶类活性,减少叶片中MDA的产生,降低幼苗死亡率,0.2%(NH4)2SO4处理效果最好,其次为0.4%(NH4)2SO4。短期低温后,使植物处在弱光环境下能减少活性氧的发生,为植物抗氧化系统达到新的平衡提供有利条件,从而减轻甚至消除低温伤害。     

Impact of Cu and Fe concentrations on oxidative damage in male infertility

Oxidative stress in the reproductive system is thought to have an effect on the fertilizing ability of sperm. The purpose of this study was to assess the interaction of iron (Fe) and copper (Cu) ions in suspected subfertile and fertile male groups and to find out the relationships of the semen parameters (sperm count, motility, and abnormal morphology), glutathione, malondialdehyde, and reactive oxygen species with these variables. Semen and blood obtained from 60 subfertile men and from 40 fertile volunteers were examined. The sperm count and motility in the subfertile male group were found lower than those in fertile male group (p<0.001). Cu levels in serum and seminal plasma in the subfertile male group were significantly higher than those in the fertile male group (p<0.001 and p<0.05, respectively). There was also a significant increase in the Fe level of seminal plasma in the subfertile male group (p<0.001). However, there was no significant difference in the Fe level of serum in the subfertile male group. In conclusion, these findings suggest that Cu and Fe might be mediators of the effects of oxidative damage and play an essential role in spermatogenesis and male infertility; the determination of Fe and Cu levels in serum and seminal plasma during infertility investigation is recommended.