慢性铅暴露对大鼠脑组织 XRCC1 mRNA 表达的影响及其与氧化应激的关系

目的 观察饮水铅暴露对大鼠大脑皮质、 小脑、 海马组织中 X 线交错互补修复基因 1（XRCC1）mRNA 表达的影响及其与氧化应激的关系。方法 40 只 SD 大鼠根据体质量按随机区组法分对照组和 4 个铅暴露组： 最低剂量组、 低剂量组、 中剂量组、 高剂量组, 对照组自由饮用去离子水, 4 个铅暴露组分别饮用 100、 200、 400、 800 mg/L 的醋酸铅溶液, 连续染毒 60 d 后取大脑皮质、 小脑和海马。RT-PCR 技术检测脑组织 XRCC1 mRNA 的表达量, 并测定脑组织铅、 过氧化氢酶 （CAT）、 谷胱甘肽 （GSH） 和过氧化氢 （H2O2） 的含量。结果 与对照组比较, 铅暴露组大鼠大脑皮质、 小脑和海马中 XRCC1 mRNA 表达量、 脑铅的含量和 H2O2水平均升高(P＜0.05); 而 CAT、 GSH 含量基本低于对照组 （P < 0.05）; 相关性分析显示铅暴露组大鼠大脑皮质、 小脑和海马中 XRCC1 mRNA 表达量与脑组织铅含量呈正相关(r 分别为 0.608、 0.438、 0.470, P＜0.01), 与 CAT、 GSH 呈负相关 （r 分别为-0.343、 -0.465、 -0.423, -0.383、 -0.489、 -0.366, P＜0.05）, 与 H2O2 呈正相关(r 分别为 0.455、 0.517、 0.342, P＜0.05)。结论 铅可通过诱导细胞氧化应激而影响 XRCC1 mRNA 的表达。     

APE1和Ki67蛋白在胃癌组织中的表达及其临床意义

目的 研究脱嘌呤脱嘧啶核酸内切酶(APE1)和细胞增殖抗原标记物Ki67蛋白在胃癌组织中的表达及其临床意义.方法 选取未经术前放、化疗的胃癌标本99例,用免疫组织化学EnVision法检测两组APE1和Ki67基因的表达,分析其与胃癌临床病理特征的关系.结果 胃癌组织APE1和Ki67蛋白的阳性表达率分别为63.6％(63/99)和64.6％(64/99);APE1和Ki67蛋白的阳性表达率与胃癌组织淋巴结转移均密切相关(P＜0.05);APE1的表达亦与胃癌组织浸润深度相关(P＜0.05);胃癌组织中APE1和Ki67蛋白两者的表达呈正相关(r=0.319,P＜0.01).结论 APE1可能是预测胃癌组织浸润、转移有用的指标;联合检测APE1和Ki67蛋白可作为判断胃癌预后和筛选高危转移患者的有效指标.     

间歇低氧合并肺气肿大鼠模型肝脏氧化应激及凝血功能的研究

目的建立肺气肿合并间歇低氧(IH)的重叠综合征(OS)大鼠模型,探讨OS大鼠肝脏炎性损伤及其凝血功能的变化。方法将60只雄性Wistar大鼠随机分成正常组(A组)、IH组(B组)、肺气肿组(C组)和IH合并肺气肿组(D组)。通过对大鼠进行16周的熏烟暴露造成大鼠肺气肿;从13周开始,同时施加程控预制的间歇低氧/再氧合(IH/ROX)处理对大鼠进行IH暴露4周。暴露结束后取各组大鼠肺和肝脏组织于光镜下观察并计算肝脏炎性损伤病理评分。取肝组织匀浆采用ELISA方法测定其超氧化物歧化酶(SOD)活性、过氧化氢酶(CAT)活性和丙二醛(MDA)浓度。检测血浆纤维蛋白原(FIB),血浆因子FⅧ促凝活性(FⅧ:C)、血管性血友病因子抗原(v WF:Ag)和抗凝血酶活性(AT:A)水平。结果 D组肝脏炎性损伤病理评分和凝血因子FIB、FⅧ:C、v WF:Ag水平均高于A、B、C组,而SOD和CAT活性以及AT:A水平低于其他3组(均P<0.05)。FIB、v WF:Ag、FⅧ:C、AT:A与SOD呈明显相关(r分别为-0.905、-0.941、-0.946和0.817,均P<0.01)。结论 OS动物模型下IH和肺气肿在导致氧化应激和高凝状态上具有一定叠加效应,可引起更强的肝脏炎症反应和血栓前状态。     

积雪草苷对大鼠缺血再灌注脑组织损伤的保护作用研究

目的 探讨积雪草苷对大鼠缺血再灌注脑组织损伤的保护作用及机制.方法 将60只15日龄SD大鼠随机分为对照组、模型组、积雪草苷低、高剂量组,每组15只.采用"线栓法"建立大鼠大脑中动脉栓塞模型,模型制作完成后积雪草苷低、高剂量组立即腹腔内注射积雪草苷(10、20 mg/kg),对照组和模型组腹腔内注射等体积生理盐水,1/...     

丹参、川芎嗪复方制剂对老年性痴呆模型大鼠红细胞及脑组织SOD、MDA的影响研究

目的:研究丹参、川芎嗪复方制剂(DCs)对老年性痴呆(AD)模型大鼠红细胞及脑组织中超氧化物歧化酶(SOD)、丙二醛(MDA)的影响。方法:以AlCl3和D-半乳糖复制AD大鼠模型,以脑复康作阳性对照,观察DCs对AD模型大鼠红细胞及脑组织SOD、MDA的影响。结果:DCs组大鼠红细胞及脑组织中SOD活性显著高于AD模型组(P<0.05或P<0.01);MDA含量显著低于AD模型组(P<0.05或P<0.01)。结论:DCs能有效提高AD模型大鼠红细胞及脑组织SOD的活性,降低MDA含量。     

基于URAT1蛋白表达研究小檗碱对高尿酸血症小鼠炎症反应及氧化应激的影响

目的 探索小檗碱对高尿酸血症小鼠炎症因子水平和氧化应激损伤的影响机制。方法 选取雄性SPF级昆明小鼠48只,分为对照组、模型组、苯溴马隆(20 mg/kg)组和小檗碱低、中、高剂量(50、100、200 mg/kg)组,每组8只。除对照组ig等量蒸馏水外,其余各组采用ig氧嗪酸钾和次黄嘌呤药物建立高尿酸血症小鼠模型,造模后苯溴马隆组ip给予20 mg/kg苯溴马隆,小檗碱低、中、高剂量组分别ig 50、100、200 mg/kg小檗碱,各组均连续给药1周。检测小鼠血清指标尿酸、肌酐(Cr)水平;ELISA法测定C反应蛋白(CRP)水平、超氧化物歧化酶(SOD)的活性及丙二醛(MDA)的含量;苏木素-伊红染色观察小鼠肾脏病理组织变化情况;Western blotting法检测肾脏尿酸转运蛋白URAT1在小鼠体内的表达水平。结果 与对照组相比,模型组小鼠血清尿酸、Cr、CRP水平、MDA含量和URAT1蛋白表达均显著升高,SOD含量明显减少(P<0.01)。与模型组相比,苯溴马隆组和小檗碱50、100、200 mg/kg组小鼠血清尿酸、Cr、CRP水平、MDA含量和URAT1蛋白表达显著降低,SOD含量明显增加(P<0.05、0.01)。小鼠肾脏HE染色结果提示,与模型组相比,小檗碱50、100、200 mg/kg组肾脏病理性改变的程度均有所缓解。而小檗碱100、200 mg/kg组与苯溴马隆组比较无明显差异。结论 小檗碱能降低高尿酸血症小鼠体内炎症水平,提高抗氧化能力。同时减轻高尿酸血症小鼠血清尿酸水平,其机制与抑制URAT1表达相关。     

麦芽醇对小鼠的毒性作用及对红细胞抗氧化酶类活性的影响

作者过去的实验结果认为麦芽醇是一个有效的抗氧化剂,可以防止红细胞自身氧化及外源氧化剂的氧化作用。本文用小鼠按50mg/kg体重喂麦芽醇,每日一次,一个月后处死,观察各脏器的变化及红细胞内抗氧化酶(超氧化物歧化酶、过氧化氢酶)活性及谷胱甘肽含量。光镜观察各脏器无改变,抗氧化酶活性增强,谷胱甘肽含量增高。另外,麦芽醇服后,小鼠游泳耐力增强。     

铅镉联合暴露对大鼠肾脏功能损伤的研究

目的 探讨铅、镉对大鼠肾脏功能损伤的联合毒性作用.方法 对大鼠进行铅(300 mgPb/L)、镉(50 mgCd/L)单独和联合(300 mgPb/L 50 mgCA/L)饮水染毒8周.检测尿液中碱性磷酸酶(UALP)、N-乙酰-β-D-氨基葡萄糖苷酶(UNAG)、γ-谷氨酰基转移酶(UGGT)活力和总蛋白(utp)、α-微球蛋白(Ua<,1>-MG)、微量白蛋白(UmAlb)含量的动态变化.结果 单独染毒除2周时Pb、Cd组Ua<,1>-MG含量与Pb组UALP活力外,其余所测指标均从染毒2周开始明显高于对照组(P＜0.05;P＜0.01),且升高幅度与染毒时间呈正相关;联合染毒组从2周开始,所测指标均明显高于对照组(P＜0.01).在整个试验过程中,联合染毒组尿酶活力和尿蛋白含量均高于单独染毒组.结论 Pb、Cd联合暴露对大鼠肾脏功能的损伤呈协同毒性效应.     

Effects of lead exposure on the expression of phospholipid hydroperoxidase glutathione peroxidase mRNA in the rat brain.

Oxidative damage associated with lead in the brain has been proposed as a possible mechanism of lead toxicity. Of the many antioxidant enzymes, phospholipid hydroperoxidase glutathione peroxidase (PHGPx) is known to protect cells from lipid peroxide-mediated damage by catalyzing lipid peroxide reduction. In this study, the effects of lead on the activity and expression of PHGPx mRNA were investigated in the brains of rats exposed to lead for 8 weeks. Male Sprague-Dawley rats (3 week old, n = 40) were randomly divided into four groups of 10 and treated with four different concentrations of lead in drinking water: a low dose (0.1% lead acetate), a medium dose (0.3% lead acetate), and a high dose (1.0% lead acetate), and a control group (0% lead acetate). We compared the four groups in terms of body and brain weight, lead concentrations in the brain and blood, and the activities of superoxide dismutase (SOD), gluthatione peroxidase (GPx), and PHGPx mRNA in the brain. Phospholipid hydroperoxidase glutathione peroxidase was found to have a dominant role in lead exposure. We also performed in situ hybridization of PHGPx mRNA in the brain to identity PHGPx mRNA active sites. We found that the level of PHGPx mRNA in brain increased in the medium- and low-dose groups, but decreased in the high-dose group versus the non-lead-treated control group. These results suggest that lead exposure increases the expression of PHGPx mRNA in the low- and medium-dose groups without inducing structural changes, and that the reduced expression of PHGPx mRNA in the high-dose group was associated with structural damage. An In situ hybridization study showed that PHGPx mRNA in the brain is expressed mainly in the white matter of the cerebral hemisphere and in the Purkinje cells of the cerebellar hemispheres; these sites are known to be the vulnerable to lead toxicity.     

硫化氢对局灶性脑缺血大鼠脑组织氧化应激的影响

目的：观察硫化氢（H2 S）对局灶性脑缺血大鼠脑组织氧化应激的影响。方法40只健康雄性 SD 大鼠,随机分为假手术（Sham）组、缺血模型（Ischemia）组、H2 S 低剂量（L-NaHS）组、H2 S 中剂量（M-NaHS）组和 H2 S 高剂量（H-NaHS）组。线栓法复制大鼠大脑中动脉闭塞模型。H2 S 低、中、高剂量组大鼠于缺血3 h 时分别腹腔注射0.7 mg/ kg、1.4 mg/ kg 和2.8 mg/ kg 的 NaHS,Sham 组和 Ischemia 组注射等容量的0.9%氯化钠溶液。5组大鼠均于缺血24 h 时断头取脑,测定脑组织中丙二醛（ MDA）的含量、超氧化物歧化酶（ SOD）的活性和谷胱甘肽过氧化物酶（GSH-PX）的活性;透射电镜观察脑组织的病理变化。结果与 Sham 组比较,Ischemia 组大鼠脑组织 SOD、GSH-PX 活性明显降低（ P ﹤0.01）,MDA 含量明显升高（ P ﹤0.01）;电镜观察显示神经元水肿,线粒体膜肿胀、线粒体嵴断裂甚至消失,线粒体大量空泡化,细胞器的数量减少;与 Ischemia 组比较,M-NaHS、H-NaHS 组大鼠脑组织中 SOD、GSH-PX活性明显升高（ P ﹤0.05）,MDA 含量明显降低（ P ﹤0.05）;电镜观察可见神经元轻度水肿,线粒体部分肿胀、内外膜结构清晰、部分嵴断裂消失,细胞器数量增多,脑缺血损伤程度明显减轻。结论 H2 S 可减轻大鼠局灶性脑缺血损伤,其机制与提高大鼠的抗氧化应激能力有关。     

仙人掌多糖组分对大鼠脑片氧化应激损伤的保护作用

目的研究仙人掌多糖对H_2O_2所致大鼠大脑皮质和海马脑片氧化应激损伤是否有保护作用。方法大鼠离体皮质和海马脑片与2mmol·L-1H_2O_2共孵育30min造成脑片的氧化应激损伤,分别于加入H_2O_2前加入仙人掌多糖作用30min,与H2O2同时加入仙人掌多糖作用30min或在H2O2损伤之后加入仙人掌多糖作用2h。TTC染色法检测脑片活性,并检测脑片培养液中乳酸脱氢酶(LDH)、超氧化物歧化酶(SOD)活性,谷胱甘肽(GSH)含量和总抗氧化能力(T-AOC)。结果H2O2孵育30min明显损伤大鼠海马和皮质脑片,TTC染色A490nm值下降,LDH释放增加,GSH含量和总抗氧化能力降低。加入H_2O_2前预先加入仙人掌多糖0.333和1.67mg·L-1作用30min显著抑制上述H2O2所致脑片损伤,使受损脑片孵育液中GSH含量增加,SOD活性和总抗氧化能力升高。结论仙人掌多糖能够减轻H2O2所致大鼠大脑皮质和海马脑片的氧化应激损伤,其机制可能与其增强机体的抗氧化能力有关。     

葛根素在减轻创伤性脑损伤氧化应激反应中的作用

目的：探究葛根素是否能有效减轻创伤性脑损伤（TBI）中的氧化应激反应。方法选择成年雄性 SD大鼠60只构建 TBI 模型并随机平分为模型组,假手术组及葛根素给药组（给药组）,每组20只。检测3组大鼠在不同时间点氧化应激相关指标[超氧化物歧化酶（SOD）、谷胱甘肽过氧化物酶（GSH－Px）、过氧化氢酶（CAT）、丙二醛（MDA）]活性及含量变化。结果氧化应激相关指标检测中,给药组与模型组比较,其中第3、7天 SOD、CAT 活性以及 MDA、NO 含量与同时间点模型组比较差异有统计学意义（ P ＜0．05）。用药组与模型组比较,均能不同程度升高GSH 含量及 GSH－Px 活性（ P ＜0．05）,其中给药组第3天及第7天 GSH 含量及 GSH－Px 活性较同时间点模型组比较差异有统计学意义（ P ＜0．05）。结论根据对不同氧化应激指标检测所得结果可以看出葛根素可有效减轻创伤性脑损伤所带来的氧化应激损伤。     

Evaluation of oxidative stress induction in rats following exposure to silver nanorods

The study investigated the oxidative stress induction by the 10 and 25?nm silver nanorods (SNRs) following intra-tracheal instillation in rats after 1?day, 1 week, 1 month and 3 months post instillation periods at 1 and 5?mg/kg b.w. doses. The blood was withdrawn by retro orbital plexus method after exposure periods and different oxidative stress markers were estimated. The results showed that the both sizes of SNRs induced increased levels of malondialdehyde (MDA) and depleted glutathione (GSH) levels after 1?day and 1 week post exposure periods. The 10 and 25?nm SNRs at both doses displayed that significantly reduced levels of superoxide dismutase (SOD) and catalase following 1?day and 1 week post exposure periods. Also, the results have shown that decrease in total antioxidant capacity (TAC) of both sizes of SNRs significantly following 1?day and 1 week post exposure periods, indicating the oxidative stress induction by SNRs. In spite, there were no significant changes in oxidative stress markers following 1 month and 3 months post exposure periods may be due to recovery. The increased levels of MDA and decreased levels of GSH, SOD, catalase and TAC activity are strongly associated to ROS production and lipid peroxidation, suggesting the induction of oxidative stress in rats. The 10?nm SNRs at 5?mg/kg b.w. dose exposures in rats have shown greater changes in all oxidative stress parameters, indicating the greater induction of oxidative stress when compared with the 25?nm SNRs, representing the size–dose-dependent induction of oxidative stress of SNRs.     

Assessment of oxidative stress induced by gold nanorods following intra-tracheal instillation in rats

Gold nanorods (GNRs) are used for their wide variety of applications in various industries. There is a little availability of data related to toxicity and ecological implications of these GNRs. The study evaluated the oxidative stress induction following intra-tracheal instillation of 1 and 5?mg/kg b.w. doses of 10 and 25?nm GNRs by estimating various oxidative stress markers including lipid peroxidation (malondialdehyde; MDA), glutathione (GSH), superoxide dismutase (SOD), catalase and total antioxidant capacity (TAC) after 1?day, 1?week, 1?month, and 3?months post exposure periods. The results have shown increased MDA levels and decreased GSH levels following 1?day and 1?week post exposure periods, indicating induction of oxidative stress. Also, the SOD, catalase and TAC levels were significantly decreased following exposure of both 10 and 25?nm GNRs after 1?day and 1?week after exposures, indicating the inhibition of antioxidant defense mechanisms. Moreover, the 10?nm GNRs at 5?mg/kg dose displayed greater changes in all the estimated parameters, representing dose and size based induction of oxidative stress by GNRs. In contrast, a little change was observed during 1?month and 3?months post exposure periods, may be due to recovery. Finally, the GNRs induced dose-size-dependent oxidative stress induction by various oxidative stress markers following intra-tracheal instillation in rats.     

Lack of reversal of oxidative damage in renal tissues of lead acetate‐treated rats

Removal of lead from the environment of man or otherwise, the movement of man from lead‐contaminated areas has been employed as a means of abatement of the toxic effects of lead. Whether toxic effects in already‐exposed individuals subside after lead withdrawal remains unanswered. To understand the reversibility of nephrotoxicity induced by lead acetate, male Wistar rats were orally exposed to 0.25, 0.5, and 1.0 mg/mL of lead acetate for 6 weeks. Activities of glutathione‐s‐transferase, catalase (CAT), superoxide dismutase (SOD) and the concentrations of hydrogen peroxide (H₂O₂), and malondialdehyde increased significantly (p < 0.05) in a dose‐dependent manner, whereas reduced glutathione (GSH) level and glutathione peroxidase activity were significantly reduced. The pattern of alterations in most of the oxidative stress and antioxidant parameters remained similar in rats from the withdrawal period, although CAT and SOD activities reduced, in contrast to their elevation during the exposure period. Serum creatinine levels were significantly elevated in both exposure and withdrawal experiments whereas serum blood urea nitrogen levels were not significantly different from the control in both exposure and withdrawal periods. The histological damage observed include multifocal areas of inflammation, disseminated tubular necrosis, and fatty infiltration of the kidney tubules both at exposure and withdrawal periods. The results suggest that lead acetate‐induced nephrotoxicity by induction of oxidative stress and disruption of antioxidant. The aforementioned alterations were not reversed in the rats left to recover within the time course of study. © 2014 Wiley Periodicals, Inc. Environ Toxicol 30: 1235–1243, 2015.     

Ameliorative effects of Bacopa monniera on lead-induced oxidative stress in different regions of rat brain

Abstract

Bacopa monniera is a rejuvenating herb for brain cells enhancing learning and cognitive ability. In the present investigation, the ameliorative effects of Bacopa monniera were examined against lead-induced oxidative stress in different regions of rat brain. Male rats were divided into five groups: control (1000?ppm sodium acetate) and exposed (1000?ppm lead acetate) for 4 weeks; DMSA (Meso-2,3-Dimercaptosuccinic acid)-treated (90?mg/kg body weight/day); Bacopa monniera-treated (BM) (10?mg/kg body weight/day) and a combination of BM?+?DMSA for seven consecutive days after 4 weeks of lead exposure. After treatment, the whole brain was isolated by sacrificing rats and four regions were separated namely cerebellum, hippocampus, frontal cortex and brain stem. Results indicated a significant (p?<?0.05) increase in reactive oxygen species (ROS), lipid peroxidation products (LPP) and total protein carbonyl content (TPCC) in association with tissue metal content in all the four regions of brain for exposed group compared with their respective controls. However, the lead-induced ROS, LPP, TPCC and tissue metal content were lowered on treatment with Bacopa monniera, almost reaching the control group values in all the above brain regions compared to DMSA and a combination therapy. Results suggest that Bacopa monniera can mitigate the lead induced-oxidative stress tissue specifically by pharmacologic interventions which encompass both chelation as well as antioxidant functions.     

Analysis of neuroglobin mRNA expression in rat brain due to arsenite-induced oxidative stress

Arsenic (As) in drinking water is a toxicant causing several health problems including nervous system disturbance. Neuroglobin (Ngb) is a tissue globin in nervous system playing protective role against oxidative stress in many injuries. This study was to investigate how long arsenite exposure (sodium arsenite 7.5 mg/kg/day) could induce oxidative stress in blood and brain of rats and to determine whether Ngb expression in rat brain changed due to oxidative stress. Results showed that superoxide dismutase (SOD) activity and malondialdehyde (MDA) level in serum and brain homogenates and reactive oxygen species (ROS) generation in red blood cells (RBCs) did not change in the rats exposed to arsenite for 8 weeks. In the rats exposed to arsenite for 16 weeks, SOD activity decreased (serum: P < 0.05; brain homogenates: P < 0.01) and MDA level increased (P < 0.01) in serum and brain homogenates; ROS production increased (P < 0.01) in RBC. When oxidative stress occurred, Ngb mRNA expression did not change in whole brain, cerebral cortex, midbrain, and hippocampus; however, Ngb mRNA expression increased significantly (P < 0.05) in cerebellum compared to the control group. This study suggests that arsenite exposure for 16 weeks can lead to oxidative stress of blood and brain of rats. Ngb may play a protective role incerebellum when oxidative stress occurs due to arsenite exposure. © 2010 Wiley Periodicals, Inc. Environ Toxicol, 2012.