褪黑素对大鼠海马神经元谷氨酸所致毒性的拮抗作用

在大鼠海马脑片上电刺激Ｓｃｈａｆｆｅｒ 侧支纤维, 胞外记录ＣＡ１ 区锥体细胞层诱发群体锋电位（ｐｏｐｕｌａｔｉｏｎ ｓｐｉｋｅ,ＰＳ） , 观察灌流谷氨酸（Ｇｌｕ） 和褪黑素（ＭＥＬ） 对ＰＳ的影响。结果显示：５－０ ｍｍｏｌ／Ｌ浓度的Ｇｌｕ 可使ＰＳ值下降至对照值的４－１ ％ ; ＭＥＬ（０－４ 、０－５ 和０－６ μｍｏｌ／Ｌ） 与５－０ ｍｍｏｌ／ＬＧｌｕ 混合给药,ＰＳ值分别变化为对照值的１４－７ ％ 、１０５－２％ 、２４－３ ％ ; ＭＥＬ（０－５ μｍｏｌ／Ｌ） 、Ｇｌｕ （５－０ ｍｍｏｌ／Ｌ） , 与赛庚啶（ＣＤＰ,０－５ μｍｏｌ／Ｌ） 混合给药,ＰＳ值下降至０ 。上述结果提示,５－０ ｍｍｏｌ／Ｌ浓度的Ｇｌｕ 有神经毒性作用, 但可为ＭＥＬ拮抗, 这可能由５ＨＴ受体所介导。     

磷酸三(1-氯-2-丙基)酯降解菌筛选及其降解特性

【背景】磷酸三(1-氯-2-丙基)酯[tris-(1-chloro-2-propyl)phosphate,TCIPP]作为全球广泛关注的新兴有机污染物,具有环境赋存含量高、不易生物降解等特点,亟须开发TCIPP的高效去除技术。【目的】获得具有较高TCIPP降解效率并可用于TCIPP污染修复的新菌株。【方法】利用梯度提高无机盐培养基中TCIPP浓度的方法,从TCIPP污染土壤中筛选出1株能够降解液体中高浓度TCIPP (100 mg/L)的菌株,根据16S rRNA基因序列分析对其进行鉴定,并首次对其降解液体中TCIPP的特性进行研究。【结果】所筛选的TCIPP降解菌株DT-6为苍白杆菌(Ochrobactrum sp.),它能够利用TCIPP作为唯一碳源和能源;当TCIPP初始浓度为50 mg/L、培养时间为7 d时DT-6的生物量最大,对TCIPP的降解率也达到最高,为34.6%;蔗糖的加入能够显著促进DT-6的生长,但却抑制了其对TCIPP的降解。【结论】本研究报道了一株TCIPP高效降解菌Ochrobactrum sp. DT-6,能够为环境中TCIPP污染的生物修复提供新的种质...     

ATP-MgCl_2对心肌缺血再灌注产生O~-_■的清除作用

McCord的研究结果表明,心肌缺血再灌注性损伤是活性氧自由基——主要是超氧阴离子自由基的毒性引起的。我们的研究证明,ATP-MgCl_2心脏冷停搏保护液在动物实验和临床心脏外科手术中,对缺血缺氧心肌有着十分满意的保护作用。 我们用电子自旋共振波谱仪(ESR)分别检测了以含氧灌注液、含氧灌注液加入SOD和含氧灌注液加入ATP—MgCl_2对离体兔心再灌注时氧自由基的变化,以阐明ATP-MgCl_2是否具有清除活性氧自由基的作用。     

131I对男性甲状腺功能亢进症血清性激素及甲状腺球蛋白水平影响研究

目的:探讨~(131)I对男性甲状腺功能亢进症患者血清性激素及甲状腺球蛋白水平的影响。方法:收集我院收治的男性甲状腺功能亢进症患者74例,随机分为对照组和实验组,每组各37例,对照组患者给予他巴唑口服,20-30 mg/次,每日口服1次。实验组患者在对照组基础上给予~(131)I治疗。治疗结束后,检测并比较两组患者血清游离三碘甲状腺素(FT3)、游离甲状腺素(FT4)、促甲状腺激素(TSH)、睾酮(T)、雌二醇(E2)、甲状腺球蛋白(TG)水平的变化以及临床疗效。结果:与治疗前相比,两组患者血清FT3、FT4、T、E2、TG水平均显著下降,TSH水平明显升高(P0.05);与对照组相比,实验组患者血清FT3、FT4、T、E2、TG水平较低,TSH水平以及临床治疗有效率较高(P0.05)。结论:~(131)I能够显著降低男性甲状腺功能亢进症血清FT3、FT4、T、E2、TG水平,升高TSH水平,临床效果较好。     

大鼠甲状腺毒症心肌肥大的细胞内钙离子分布的研究

采用人工大鼠腹腔注射Ｌ－甲状腺素３周、４周不等,发现实验组大鼠心肌细胞线粒体内有大量Ｃａ２＋沉淀物积聚,多呈弥漫性散在分布,亦可沿线粒体嵴呈线样排列。结果提示：细胞内Ｃａ２＋积聚和异常分布与细胞损害程度密切相关。     

邻苯二甲酸二(2-乙基己基)酯对大鼠胎盘组织的影响

目的:探讨孕期不同剂量邻苯二甲酸二(2-乙基己基)酯(DEHP)暴露对大鼠胎盘组织形态学和超微结构的影响,以推断DEHP对胎盘结构和功能的损害。方法:健康雌性Wistar大鼠40只,随机分为4组,妊娠第11日起每日给予DEHP灌胃,剂量分别为:对照组(玉米油)、低剂量组(100 mg/kg)、中剂量组(500 mg/kg)和高剂量组(1000 mg/kg),妊娠第19日处死孕鼠,取胎盘组织分别做HE染色和电镜制片,观察各剂量组胎盘形态学及超微结构的变化。结果:各剂量组胎盘形态学和超微结构的变化与DEHP摄入量呈负相关,低剂量组胎盘无明显改变;中剂量组胎盘缩小,空泡化细胞增多,微观结构显示胞质内线粒体水肿;高剂量组胎盘迷路带血窦扩张淤血严重,滋养细胞变性、坏死。结论:DEHP可导致大鼠胎盘形态结构发生改变,这种病理改变是胎盘功能减退的形态学基础,可直接影响胚胎发育和妊娠结局。     

Fisetin对H_2O_2诱导细胞内ROS的清除作用及机制探讨

活性氧(reactive oxygen species, ROS)在非酒精性脂肪肝、心血管疾病、癌症、糖尿病等疾病发生发展的过程中具有重要作用。HepG2细胞是评价抗氧化剂对活细胞氧化损伤保护作用的常用细胞模型。为了探讨非瑟酮(fisetin)对H_2O_2诱导细胞内ROS的清除作用及其机制,将HepG2细胞随机分为空白对照组(control)、溶剂对照组(solvent control)、H_2O_2模型组(H_2O_2model group)、fisetin干预组(fisetin+H_2O_2)、fisetin单独处理组(fisetin),检测不同干预组细胞存活率大小及细胞内ROS水平,同时检测核因子E2相关因子2 (nuclear factor erythroid 2-related factor 2, Nrf2)、Kelch样ECH相关蛋白1 (Kelch-like ECH-associated protein 1, Keap1)及Ⅱ相酶血红素氧合酶-1 (heme oxygenase-1, HO-1)、谷氨酰半胱氨酸连接酶催化亚基(glutamate-cysteine ligase catalytic subunit,GCLC)、谷氨酰半胱氨酸连接酶修饰亚基(glutamate-cysteine ligase modifier subunit, GCLM)、醌氧化还原酶1(NAD(P)H quinone oxidoreductase 1, NQO1)的表达。此外,通过构建Nrf2敲低细胞系,进一步明确Nrf2在fisetin清除ROS过程中的作用。研究发现,与H_2O_2模型组相比, fisetin干预组细胞存活率显著上升; fisetin可抑制由H_2O_2引起的HepG2细胞内ROS的增加,上调Nrf2、HO-1蛋白表达,并下调Keap1蛋白表达; Nrf2稳定敲低后,细胞内ROS水平增加。实验结果表明, fisetin可能通过激活Keap1/Nrf2/抗氧化反应元件(antioxidant response element, ARE)通路诱导HO-1的表达,从而在抗氧化损伤过程中发挥细胞保护作用。     

牡丹花水提液对氧自由基的清除作用

牡丹花水提液加入O 2和·OH的产生及检测系统中,能显著降低介导的氮兰四唑(NBT)的光化学还原和·OH作用下的水杨酸羟基化作用.这提示牡丹花水提液具有显著的清除氧自由基的活性,红色牡丹花水提液清除氧自由基的效能高于浅色花.     

金耳菌丝体多糖对实验性2型糖尿病大鼠的降血糖作用研究

本文研究了金耳菌丝体多糖(TMP)对实验性2型糖尿病大鼠血糖、血脂、胰岛素敏感性和抗氧化能力的影响。采用烟酰胺,链脲佐菌素和高脂饲料诱导2型糖尿病大鼠模型,以50和100mg/(kg.d)剂量的TMP连续灌胃48d,监测血糖,测定血清胰岛素、体重、脂代谢及抗氧化系统部分相关指标,并进行口服糖耐量实验。结果显示,TMP可明显降低2型糖尿病大鼠的血清葡萄糖、总胆固醇、甘油三酯和丙二醛水平,并极显著提高受试模型鼠的胰岛素敏感指数,血清超氧化物歧化酶活性和肝脏过氧化氢酶活性。此外,TMP能显著降低糖耐量实验中糖负荷后120min时糖尿病大鼠的血糖含量。上述结果表明TMP可有效降低实验性2型糖尿病大鼠的血糖水平,纠正脂代谢紊乱,改善胰岛素抵抗,增强抗氧化能力。     

脂多糖对大鼠多巴胺能神经元毒性作用的研究

目的　建立新的帕金森病 (Parkinson’sdisease ,PD)动物模型 ,探讨其发病机制。方法　在大鼠脑黑质(substantianigra ,SN)内注射脂多糖 (Lipopolysaccharide ,LPS)后 ,按大鼠不同存活期用高效液相色谱 (HPLC)来测定脑内多巴胺 (Dopamine,DA)及其代谢产物的含量 ;用免疫组化法观察酪氨酸羟化酶 (Tyrosinehydroxylase ,TH)阳性神经细胞、小胶质细胞的形态及数量变化。结果　DA及其代谢产物的含量在LPS注射侧随时间不同有不同程度下降 ,于第 14天达到最低 (P <0 0 1) ;注射侧黑质TH阳性神经元可以达到全部消失 ,该处可见大量被激活并有形态改变的小胶质细胞。结论　LPS可导致大鼠黑质多巴胺能神经元的损害     

Evaluating the toxic potential of agrochemicals on the hypothalamic-pituitary-thyroid axis in tilapia (Oreochromis mossambicus)

Agrochemicals are a major cause of concern for the aquatic environment because of their toxicity, persistence, and tendency to accumulate in the organisms. The impact of these chemicals on aquatic organisms is due to their movement from various diffuse or point sources, which poses a great threat to aquatic fauna especially fishes, which constitute one of the major sources of protein-rich food for mankind. The present study is a first of its kind, where the toxic potential of two sublethal concentration (LC_1/10th and LC_1/25th) of four different classes of agrochemicals have been tested (Insecticide- Imidacloprid-0.074 ppm, 0.02 ppm, Fungicide-Curzate- 4.9 ppm, 1.96 ppm, Herbicide- Pyrazosulphuron ethyl-50 ppm, 20 ppm and Fertilizer-Micronutrient mixture 500 ppm, 200 ppm) on candidate markers of hypothalamus pituitary-thyroid axis (TSH, T₃, T₄, TSHβr) in Oreochromis mossambicus (tilapia) by validating hormonal level and mRNA expression. The results reveal that exposure to agrochemicals resulted in a broad range of alterations with maximum damage being caused by insecticide followed by herbicide and fungicide in that order on the thyroid axis. The results of the present study highlight the need for more detailed studies on the effects of agrochemicals that accumulate in organisms and propose that there should be a check on the rampant use of agrochemicals.     

Chronological changes in tissue copper, zinc and iron in the toxic milk mouse and effects of copper loading

The toxic milk (tx) mouse is a rodent model for Wilson disease, an inherited disorder of copper overload. Here we assessed the effect of copper accumulation in the tx mouse on zinc and iron metabolism. Copper, zinc and iron concentrations were determined in the liver, kidney, spleen and brain of control and copper-loaded animals by atomic absorption spectroscopy. Copper concentration increased dramatically in the liver, and was also significantly higher in the spleen, kidney and brain of control tx mice in the first few months of life compared with normal DL mice. Hepatic zinc was increased with age in the tx mouse, but zinc concentrations in the other organs were normal. Liver and kidney iron concentrations were significantly lower at birth in tx mice, but increased quickly to be comparable with control mice by 2 months of age. Iron concentration in the spleen was significantly higher in tx mice, but was lower in 5 day old tx pups. Copper-loading studies showed that normal DL mice ingesting 300 mg/l copper in their diet for 3 months maintained normal liver, kidney and brain copper, zinc and iron levels. Copper-loading of tx mice did not increase the already high liver copper concentrations, but spleen and brain copper concentrations were increased. Despite a significant elevation of copper in the brain of the copper-loaded tx mice no behavioural changes were observed. The livers of copper-loaded tx mice had a lower zinc concentration than control tx mice, whilst the kidney had double the concentration of iron suggesting that there was increased erythrocyte hemolysis in the copper-loaded mutants.     

Retinoic acid effects on thyroid function of female rats

AimsRetinoic acid is widely used in dermatological treatment and thyroid cancer management; however its possible side-effects on normal thyroid function remains unknown. We aimed to determine the effects of retinoic acid on thyroid function of adult female rats.Main methodsFemale Wistar rats were treated with all-trans-retinoic acid and 13-cis retinoic acid for 14 and 28 days. Then, rats were killed and thyroid function was evaluated.Key findingsSerum T4 and thyrotropin levels remained unchanged, while serum T3 increased in animals treated with all-trans-retinoic acid for 14 days. No changes were observed in hepatic or renal type 1 iodothyronine deiodinase (D1) activities, while thyroid D1 was higher in animals treated for 14 days with all-trans-retinoic acid, which could be related to the increased serum T3 levels. 13-cis retinoic acid increased thyroid iodide uptake after 28 days. These results show effects of retinoic acid treatment on these thyroid proteins: sodium/iodide symporter and deiodinase.SignificanceRetinoic acid is able to interfere with normal thyroid function, increasing thyroid type 1 deiodinase activity, serum T3 levels and sodium/iodide symporter function. However, the effects are time- and retinoic acid isomer-dependent. Since serum thyrotropin levels did not change in any group, the effects observed are probably mediated by a direct retinoic acid effect on the normal thyroid.     

Region-specific effects of hypothyroidism on the relative expression of thyroid hormone receptors in adult rat brain

The aim of this study was to determine whether changes in the circulating thyroid hormone (TH) and brain synaptosomal TH content affected the relative levels of mRNA encoding different thyroid hormone receptor (TR) isoforms in adult rat brain. Northern analysis of polyA⁺RNA from cerebral cortex, hippocampus and cerebellum of control and hypothyroid adult rats was performed in order to determine the relative expression of all TR isoforms. Circulating and synaptosomal TH concentrations were determined by radioimmunoassay. Region-specific quantitative differences in the expression pattern of all TR isoforms in euthyroid animals and hypothyroid animals were recorded. In hypothyroidism, the levels of TRα2 mRNA (non-T₃-binding isoform) were decreased in all brain regions examined. In contrast the relative expression of TRα1 was increased in cerebral cortex and hippocampus, whereas in cerebellum remained unaffected. The TRβ1 relative expression in cerebral cortex and hippocampus of hypothyroid animals was not affected, whereas this TR isoform was not detectable in cerebellum. The TR isoform mRNA levels returned to control values following T₄ intraperitoneal administration to the hypothyroid rats. The obtained results show that in vivo depletion of TH regulates TR gene expression in adult rat brain in a region-specific manner. (Mol Cell Biochem 278: 93–100, 2005)     

甲状腺素对大鼠心脏细胞蛋白激酶C信号途径的影响

目的 :探讨甲状腺素对新生大鼠心脏细胞中蛋白激酶C(proteinkinaseC ,PKC)信号途径的影响。 方法 :培养新生大鼠心肌细胞及成纤维细胞 ,用 1%血清培养基或血管紧张素Ⅱ(angiotensinⅡ ,AngⅡ)处理细胞 2 4h后 ,加入甲状腺素(三碘甲状腺素原氨酸 ,triiodothyronine,T3 )继续培养 4 8h后 ,用PKC活性检测试剂盒检测细胞中PKC活性 ,用West ernblot的方法检测细胞中PKCα及PKCε的表达。结果 :在 1%血清培养基中 ,T3 能明显抑制心肌细胞中PKC活性 ,使心肌细胞中PKCε表达下降 ,对PKCα的表达却没有显著的影响 ;在心肌成纤维细胞中 ,无论是PKC活性还是PKCα及PKCε的表达均未观察到T3 的调控作用。预先用AngⅡ处理 2 4h后 ,心肌细胞及心肌成纤维细胞中PKC活性明显增加 ,PKCε的表达显著增加 ,随后用T3 处理后 ,心肌细胞中PKC活性及PKCε的表达明显降低 ;而心肌成纤维细胞中PKC活性没有发生显著性的变化。结论 :甲状腺素能明显抑制心肌细胞中PKC活性及PKCε亚型的表达 ,其对心肌细胞中PKC信号途径的调控作用可能在心肌的多种病理生理过程中起着重要的作用。     

Early larval development and metamorphosis in the summer flounder: changes in per cent whole-body water content and effects of altered thyroid status

At the end of premetamorphosis, summer flounder Paralichthys dentatus larvae had 84·1% whole-body water content (WBW), which decreased to the lowest levels (8·5%) at the start of metamorphic climax (MC). During mid- and late MC, %WBW was slightly higher (82·1%) then returned to the lowest levels at the juvenile stage. In fish treated with thyroxine (T₄-Na salt, 100 ng ml⁻¹) beginning at premetamophosis, %WBW never differed from controls of the same age throughout metamorphosis, despite an earlier start of metamorphic climax and transitional settling behaviour. This suggests that thyroid hormones do not mediate the drop in %WBW which accompanies natural metamorphosis. Thiourea (TU, 30 μg ml⁻¹) treatment of fish over the same period induced a developmental stasis in early MC which was accompanied by initially higher %WBW than controls at 33 days post-hatch, followed by a progressive decrease to abnormally low %WBW by 42 and 45 days post-hatch. Since concurrent treatment with TU+T₄ rescued the fish from both the TU-induced developmental stasis and abnormally low %WBW, these findings suggest that thyroid hormones, or thyroid hormone-mediated developmental progression, are necessary for regulating %WBW.     

Effects of oral zinc and magnesium supplementation on serum thyroid hormone and lipid levels in experimentally induced diabetic rats

This study was designed to investigate the effects of oral zinc and magnesium supplementation on serum thyroid hormone and lipid levels in alloxan-induced diabetic rats. Thirty-two albino male rats, weighing 234±34 g, were divided into four experimental groups (control, diabetic, diabetic+zinc supplemented and diabetic+ magnesium supplemented). The experiment lasted for 60 d. The first 45 d of the experiment was the supplementation and last 15 d was the supplementation and diabetes-inducing period. Diabetic+zinc-supplemented and diabetic+magnesium-supplemented groups were given orally (by adding in their drinking water) 227 mg/L of zinc and 100 mg/kg body weight (bw) of magnesium, respectively throughout the experiment. Control and diabetic groups served as controls and did not receive zinc or magnesium supplementation. Diabetic, diabetic+zinc-supplemented, and diabetic+magnesium-supplemented groups were given a daily injection (ip) of 100 mg/kg bw of alloxan for 15 d starting on d 46 of the experiment. The control group was only injected with the same volume of isotonic NaCl as the diabetic group received. At the end of the of the experiment, rats in all four groups were fasted for 12 h and blood samples were taken from the heart under ether anesthesia for the determination of thyroid hormone, glucose, total cholesterol, and triglyceride concentrations. It was found that serum glucose, total cholesterol, and triglyceride concentrations were higher and serum T3 and T4 concentrations were lower in diabetic rats than those in the control group. Zinc supplementation did not change any parameter in diabetic rats. However, magnesium supplementation decreased the elevated total cholesterol and triglyceride concentrations of the diabetic rats to the control level. It was concluded that oral magnesium supplementation might decrease the diabetes-induced disturbances of lipid metabolism.