噪声习服对豚鼠耳蜗抗氧化酶的影响

目的探讨噪声习服对耳蜗抗氧化酶的影响。方法40只雄性豚鼠随机分为无噪声对照组(A组),噪声习服组(B组),噪声习服 强噪声暴露组(C组),单纯强噪声暴露组(D组)。B组动物在声压级为90 dB SPL (声压级)、中心频率为0.5 kHz的一个倍频程噪声下连续暴露10 d,每天6 h;C组动物在经过与B组相同的噪声习服处理后,休息5d,再暴露于105 dB的白噪声4 h;D组动物直接暴露于105 dB的白噪声4 h。噪声暴露结束后即刻测定耳蜗中的脂质过氧化物酶(GSH-Px)活力。结果D组的丙二醛(MDA)水平明显高于其他3组,A、B、C、D组水平分别为144.19±4.59,147.12±4.51,163.76±4.83,187.11±6.14(P<0.05):噪声暴露后C、D组的超氧化物歧化酶(SOD)和GSH-Px活力均有所增强,C组明显高于D组分别为282.20±22.46 vs 243.95±16.53;32.72±2.24 vs 26.84±2.22(P<0.05);D组的过氧化氢酶(CAT)活力明显低于其他3组。而C组的CAT活力增强,A、B、C、D 4组CAT活力分别为63.18±4.59,65.93±4.41,82.34±4.66和45.60±4.88(P<0.05)。结论噪声习服可以提高耳蜗抗氧化酶的活力。     

钻井井场噪声暴露对豚鼠耳蜗的影响

目的预防钻井井场噪声所致的听力损伤。方法对油田钻井井场的特定部位进行声强测定及频谱分析，采用隔音、减震和改变钻井平台布局等措施，观察钻井井场噪声暴露对豚鼠听器的影响。对暴露后的豚鼠进行耳蜗电图及扫描电镜观察。结果耳蜗电图ＡＰＮ１潜伏期无明显差别。隔音房组和移动组阈值与柴油机旁组相比，差异有非常显著性，钻井平台组和与钻井平台垂直组差异无显著性。柴油机旁组与钻井平台组扫描电镜下毛细胞损伤较重，表现为外毛细胞静纤毛倾倒、脱落，以第二、第三排为著，内毛细胞部分脱落；隔音房组与移动组基本正常；与钻井平台垂直组仅见第三排毛细胞倒伏。结论动物实验证明，该措施是行之有效的，建议进一步推广应用。     

噪声对豚鼠耳蜗血流的影响

本文利用氢清除法观察了噪声对豚鼠耳蜗血流的影响。暴露丁■KHz115dB或124.5dBSPL 噪声中30分钟后,耳蜗血流显著降低,切断同侧颈交感神经后,声暴露虽也引起耳蜗血流一定程度的下降,但与对照组相比无显著差别。结果提示耳蜗血流下降可能是声损伤的原因之一,噪声可能通过交感神经系统引起耳蜗血流的减少。     

脉冲噪声暴露与耳蜗血流

人们围绕着噪声对耳蜗血流的影响做了不少工作,但结果相互矛盾,而且有关脉冲噪声对耳蜗血流影响的报道很少,对噪声引起的耳蜗血流的改变与听力及毛细胞损伤之间的关系也尚未明了。为此我们设计了本实验。以期进一步了解脉冲噪声对耳蜗血流的影响,以及耳蜗血流改变与听力及毛细胞损伤之关系。     

维生素C对豚鼠噪声性听力损失的预防作用

目的 研究维生素C对噪声性听力损失是否具有预防作用。方法 40只雄性花色豚鼠随机分为5组，每组8只。其中3组接受噪声暴露，分别腹腔注射生理盐水、维生素C(10．0，50．0mg／kg)；另2组无噪声暴露，分别腹腔注射生理盐水、维生素C(50．0mg／kg)。比较噪声暴露后各组豚鼠听觉脑干反应(ABR)的阈移，评价维生素C对噪声性听力损失的预防作用。结果腹腔注射10．0，50．0mg／kg维生素C可在一定程度上减少噪声对豚鼠引起的ABR阈值增高。结论 维生素C具有一定的预防噪声性听力损失的作用。     

噪声性听力损失与豚鼠耳蜗Bcl-2/Bax的相关性分析

摘要:目的　研究噪声暴露对豚鼠耳蜗Bcl-2、Bax 基因的表达及Bcl-2/Bax的影响,探讨噪声性听力损失（NIHL）的细胞凋亡机制。方法　36只SPF级健康雄性豚鼠随机分为对照组、95 dB、115 dB声压级（SPL）暴露组3组,每组12只,除对照组外分别予以95 dB、115 dB SPL的高斯白噪声暴露（28 d、6 h/d）,暴露前1 d和暴露结束后d 7,分别进行听性脑干反应（ABR）测量、暴露结束后d 7进行耳蜗病理学检查和荧光实时定量逆转录-聚合酶链反应（RT-PCR）法分析耳蜗Bcl-2、Bax mRNA的相对表达水平。结果　3组间豚鼠永久性听阈位移（PTS）水平比较,差异有统计学意义（χ2＝26.70,P＜0.0001）,95 dB、115 dB SPL组豚鼠耳蜗PTS水平分别为（12.50±2.50）、（27.50±2.50）（Md±（P75-P25））;病理学显示噪声暴露组的豚鼠耳蜗毛细胞和螺旋神经节细胞出现明显损伤,高强度噪声暴露损伤程度比低强度暴露严重;Bcl-2、Bax mRNA表达水平和Bcl-2/Bax比值,在3组间均有统计学差异（χ2＝20.35、22.89、23.48,P＜0.0001）;Bcl-2 mRNA表达水平随着噪声暴露强度的增加而下调;Bax mRNA表达水平在噪声暴露为115 dB SPL组显著上调;Bcl-2/Bax比值在95 dB和115 dB SPL两噪声暴露组中,均明显低于对照组,而且随着噪声暴露强度的增加而减少。结论　NIHL可诱导耳蜗细胞凋亡的发生,Bcl-2/Bax可作为评价耳蜗凋亡水平的指标。     

高频连续噪声对豚鼠听阈及耳蜗结构的影响

目的研究高频连续噪声暴露对豚鼠听阈及耳蜗结构的影响。方法16只雄性花色豚鼠随机分为噪声暴露组和对照组,每组8只豚鼠。噪声暴露组豚鼠于噪声暴露前测定听觉脑干反应阈值(auditorybrainstem responses,ABR),每日接触中心频率为4 kHz、倍频程、100 dB(A)声压级(sound pressure level,SPL)连续噪声,每天8 h,连续7 d;末次噪声暴露结束后第8天,测定ABR后处死豚鼠,取耳蜗,进行组织病理学、透射电镜及扫描电镜的观察。对照组豚鼠不接触噪声,于相应时间点测定ABR,其他处理同噪声暴露组。结果噪声暴露组豚鼠在2,4,8 kHz处的阈移分别为13.4,31.3,31.9,耳蜗外毛细胞静纤毛发生散在缺失、倒伏,胞浆萎缩、空化,细胞核萎缩或消失,部分线粒体消失,个别线粒体发生髓样变。结论噪声暴露可提高豚鼠的听阈并对其耳蜗结构具有损伤作用。     

TDW2—100穿甲弹爆震对豚鼠听力影响和耳蜗肌动蛋白免疫组…

豚鼠分别暴露于发射ＴＤＷ２－１００穿甲弹５９式坦克车内和穿甲弹击穿坦克靶车内时的强脉冲噪声中。发射穿甲弹的坦克车内脉冲声为１７０．０ｄＢ（ＳＰＬ），９发；击穿坦克靶车脉冲声大于１９４．０ｄＢ（ＳＰＬ），５发。用听生理脑干反应阈值来确定听力损失程度，并用ＡＢＣ免疫组织化学方法观察耳蜗内肌动蛋白免疫活性变化。结果是：震后８ｈ发射车内豚鼠听力下降平均为１１ｄＢ，４８ｈ全部恢复；而被击穿靶车内豚鼠听力下降     

TDW2－100穿甲弹爆震对豚鼠听力影响和耳蜗肌动蛋白免疫组织化学变化

豚鼠分别暴露于发射ＴＤＷ２－１００穿甲弹５９式坦克车内和穿甲弹击穿坦克靶车内时的强脉冲嗓声中。发射穿甲弹的坦克车内脉冲声为１７０．０ｄＢ（ＳＰＬ），９发；击穿坦克靶车脉冲声大于１９４．０ｄＢ（ＳＰＬ），５发。用听生理脑干反应阈值来确定听力损失程度，并用ＡＢＣ免疫组织化学方法观察耳蜗内肌动蛋白免疫活性变化。结果是：震后８ｈ发射车内豚鼠听力下降平均为１１ｄＢ，４８ｈ全部恢复；而被击穿靶车内豚鼠听力下降平均７５ｄＢ，４８ｈ听力下降平均４４ｄＢ。震后４８ｈ，靶车内豚鼠耳蜗毛细胞内肌动蛋白免疫活性明显下降，而发射车内豚鼠耳蜗毛细胞内肌动蛋白免疫活性与对照组无差异。结果提示：坦克靶车内瀑震声明显大于发射坦克车内爆震声。耳蜗毛细胞内肌动蛋白免疫活性与听性脑干反应阈值有一定的关系，表明，强脉冲声伤致代谢障碍在耳损伤中占有重要地位。在临床上应注意积极维护内耳代谢，或许会减少强脉冲声的损伤作用。     

噪声性听力损失与耳蜗外毛细胞Prestin蛋白的相关性分析

目的探讨噪声性听力损失(NIHL)与耳蜗外毛细胞Prestin蛋白表达的关系。方法将60只成年豚鼠随机分5组,除对照组外分别予以不同噪声声压级(85、95、105、115 d B SPL)的高斯白噪声暴露(28 d,6 h/d),而后检测听性脑干反应(ABR)以确定听阈位移水平,同时进行耳蜗病理学检查,采用免疫组化法分析耳蜗外毛细胞Prestin蛋白表达水平。结果各组豚鼠平均永久性听阈位移水平变化随着噪声暴露声压级的增强而增加(F=308.655,P0.01),强噪声声压级组(105 d B SPL)豚鼠的病理形态学显示明显的毛细胞损失,Prestin蛋白表达水平在高于95 d B SPL时随着噪声暴露声压级的增加而上调(F=700.072,P0.01)。结论耳蜗外毛细胞Prestin的表达增高,与耳蜗外毛细胞损失程度有关。     

Erythrocyte antioxidant enzyme activities in coal miners from three French regions

This study investigated whether differences in the prevalence and severity of coal workers' pneumoconiosis (CWP) between three coal mines could be related to differences in oxidative stress exposure as evaluated in vivo through red-blood-cell antioxidant enzyme activities. Blood samples were obtained from 229 miners selected according to their occupation and their pneumoconiotic status. The following biomarkers were evaluated: erythrocyte catalase, Cu²⁺/Zn²⁺ superoxide dismutase (Cu²⁺/Zn²⁺ SOD), and glutathione peroxidase activities. Antioxidant enzyme activities did not differ significantly between the group of surface workers in Lorraine and the group of underground miners without CWP in Lorraine and in the other coal mines. Erythrocyte Cu²⁺/Zn²⁺ SOD activity was slightly decreased in the group of active underground miners with simple pneumoconiosis as compared with the group of miners without CWP in Nord/Pas-de-Calais. No effect was seen between retired miners at different stages of CWP. Our findings indicate that differences in the prevalence and severity of CWP do not seem to be related to various oxidative activities of coal dust particles, at least as reflected by measurements of antioxidant enzyme activities in circulating erythrocytes in this study. Received: 3 March 1997 / Accepted: 14 October 1997     

抗氧化物质在辐射防护中的作用

电离辐射对生物体构成损伤,一是辐射能量传递的直接作用,二是通过水在辐解反应中产生的自由基所引起的损伤的间接作用,氧化损伤是辐射对机体损伤的重要机制之一。抗氧化物质可以清除自由基,理应具有辐射防护作用。     

Effects of heavy metals on production of thiol compounds and antioxidant enzymes in Agaricus bisporus

In a pre-experiment, Agaricus bisporus mycelia grown in PDL medium were found to have a substantial ability to tolerate and accumulate heavy metals. In the study, we investigated changes in the contents of soluble protein and thiol compounds as well as the activities of antioxidant enzymes caused by copper, zinc, lead, and cadmium (nitrate salts) in mycelia of A. bisporus during short-and long-term exposure. Results showed that high-level metal concentrations significantly decrease the contents of soluble protein after long-term exposure, Cu and Zn concentrations significantly increase the thiol compounds levels after long-term exposure, while high-level Cd significantly decrease thiol compounds after long-term exposure. Additionally, SOD activities were significantly increased after long-term exposure to metals, especially to Cd. The CAT activities were enhanced after long-term exposure to low-level Cu and high-level Zn, and enhanced after short-and long-term exposure to high-level Pb. The POD activities were significantly increased after long-term exposure to metals, and increased after short-term exposure to Cd and high-level Pb.     

Combined effects of high-fat diet and ethanol induce oxidative stress in rat liver

Individuals affected by liver steatosis seldom have symptoms of liver injury, but may be particularly vulnerable to oxidative insults. In this study, we evaluated liver redox alterations produced by acute ethanol administration to rats that were fed a high-fat diet (HFD). Adult male Wistar rats were fed HFD or standard diet (controls) for 1 month; a group of animals from each condition were gavaged with 35% (vol/vol) ethanol every 12 h for the last 3 days of the experiment. Total lipid content determined in liver showed lipid accumulation after HFD or HFD combined with ethanol. HFD alone induced a significant rise of seric alanine aminotransferase levels and a marked reduction of antioxidant enzyme activities (catalase, superoxide dismutase, glutathione transferase). Ethanol alone caused a significant rise of seric cholesterol levels and enhanced mitochondrial H₂O₂ production, but without apparent oxidative stress as evaluated by thiobarbituric acid-reactive substances (TBARS) assay. The combination of HFD and acute ethanol caused an increase of TBARS, indicating lipid peroxidation, most likely as a consequence of a decrease in antioxidant defenses induced by HFD and of an increase in reactive oxygen species production induced by ethanol. Principal component analysis, based on all the measured parameters, that is, serum liver function tests, antioxidant enzyme activities, mitochondrial H₂O₂ release, and TBARS, indicated that HFD and ethanol act as two independent factors. In conclusion, our results show that HFD or acute ethanol alone produce, at the most, mild liver injury, whereas their combination triggers oxidative stress, possibly inducing a progression toward liver disease. Hence, our data indicate that a diet too rich in fat is a serious risk factor for the occurrence of liver injury deriving from acute ethanol consumption.     

噪声性听力损失大鼠耳蜗miRNA调控网络分析

摘要:目的　通过噪声性听力损失（NIHL）耳蜗差异性miRNA构建的基因调控网络,分析NIHL耳蜗的重要基因及功能,探讨NIHL的损伤机制。方法　6只SPF及SD大鼠通过110 dB SPL（6 h/d、24 d）的高斯白噪声暴露建立NIHL模型,6只SPF及SD大鼠非噪声暴露作对照,噪声暴露后7 d取实验大鼠耳蜗组织进行sRNA深度测序,分析差异性表达的miRNA,以差异最显著的8个miRNA依据靶基因数据库TargetScan、miRanda和miRDB共同预测的靶基因建立差异性表达miRNA的靶基因集,结合蛋白互作数据库构建miRNA调控网络,统计网络中每个基因相连基因的个数,确定相连基因个数大于30的基因作为NIHL大鼠耳蜗的重要基因,通过GeneCards数据库对重要基因进行功能注释。结果　（1）噪声暴露组大鼠永久性听阈位移水平（PTS）明显高于对照组（秩和检验:Z值-2097,P＜0.01）;（2）sRNA测序结果显示2组耳蜗差异性miRNA有148个［|log2（Fold Change）|＞1］,差异性最显著的8个miRNA为:rno-miR-378b、rno-miR-211-5p、rno-miR-133b-3p、rno-miR-29c-3p、rno-let-7c-2-3p、rno-miR-674-5p、rno-miR-495、rno-miR-3068-3p;（3）miRNA调控网络中的重要基因有11个:VEGFA、TNF、EGFR、FOS、NR3C1、AGT、CREBBP、PTK2、CD44、STAT3、IGF1。结论　NIHL大鼠耳蜗的11个重要基因通过调控细胞增殖与分化、控制细胞凋亡、改善组织细胞营养代谢、介导组织炎性反应以改善和修复耳蜗组织细胞。     

Enzymatic antioxidant system in vascular inflammation and coronary artery disease

In biological systems there is a balance between the production and neutralization of reactive oxygen species(ROS). This balance is maintained by the presence of natural antioxidants and antioxidant enzymes suchas superoxide dismutase(SOD), catalase and glutathione peroxidase. The enhancement of lipid peroxidation or the decrease of antioxidant protection present in metabolic diseases or bad lifestyle can induce endothelial dysfunction and atherosclerosis.Clinical studies have shown that oxidative stress can increase ROS reducing the formation of antioxidant defences, especially in subjects with coronary artery disease(CAD). Some observation indicated that in the early stages of the disease there is a homeostatic upregulation of the antioxidant enzyme system in response to increased free radicals to prevent vascular damage.As soon as free radicals get to chronically elevated levels, this compensation ceases. Therefore, SOD and the other enzymes may represent a good therapeutic target against ROS, but they are not useful markers for the diagnosis of CAD. In conclusion antioxidant enzymes are reduced in presence of metabolic disease and CAD. However the existence of genes that promote their enzymatic activity could contribute to create new drugs for the treatment of damage caused by metabolic diseases or lifestyle that increases the plasma ROS levels.     

不同粒径二氧化钛对小鼠活性氧水平的影响

目的 观察不同粒径二氧化钛(TiO2)对小鼠活性氧(ROS)水平的影响.方法 48只健康雄性昆明种小鼠随机分为对照组(四蒸水)、50 nm TiO2组(5 g/kg)、120 nm TiO2组(5 g/kg).灌胃染毒后观察1周,用微波消解-电感耦合等离子体质谱(ICP-MS)法测定肝、肾、皮层及海马各组织中钛元素的含量,用流式细胞仪测定各组织细胞中ROS的含量.结果 各组小鼠一般状况良好,饮水量、进食量未见明显改变,体重增重及肝、肾、脑的脏器系数与对照组的差异无统计学意义(P>0.05).50、120 nm TiO2处理后,小鼠肝、肾、皮层、海马各组织中Ti含量明显高于对照组,差异有统计学意义(P<0.05);且50 nm处理组的Ti含量明显高于120 nm处理组,差异有统计学意义(P<0.05);50、120 nm TiO2组小鼠肝脏、肾脏和皮层组织细胞中ROS水平(273.2±32.5、160.2±28.5、74.9±8.9,159.4±15.9、64.4±7.5、41.2±5.6)与对照组(74.9±6.4、24.9±2.8、32.8±3.1)相比明显升高;50 nm处理组小鼠海马细胞中ROS水平与对照组相比明显升高,差异均有统计学意义(P<0.05);且50 nm组各组织中ROS水平明显高于120 nm组,差异亦有统计学意义(P<0.05).结论 不同粒径TiO2经口急性染毒后Ti元素可以分布于小鼠肝、肾、脑组织中,使小鼠肝脏、肾脏、皮层和海马细胞中ROS生成增加,且 50 nm TiO2的作用明显大于120nm TiO2.     

叔丁基过氧化氢体外模拟噪声引起的耳蜗毛细胞氧化损伤模型的建立

目的 研究有机氧化剂叔丁基过氧化氢(t-BHP)体外模拟噪声对耳蜗毛细胞的氧化损伤.方法 用t-BHP染毒,设置从30～4000 μmol/L8个染毒浓度对耳蜗毛细胞(HEI-OC1)细胞染毒12h,绘制100 μmol/L浓度组染毒时间(1～96 h)与耳蜗毛细胞存活率曲线;采用台盼蓝染色法检测细胞存活率,噻唑蓝(MTT)试验检测细胞增殖能力的改变,2’-7’-二氯荧光黄双乙酯(DCFH-DA)探针法检测胞内活性氧(ROS)水平.结果 不同浓度的t-BHP对耳蜗毛细胞染毒12h后,100μmol/L以上浓度组细胞存活率开始出现有统计学意义的下降,其中200～2000μmol/L浓度组细胞存活率呈直线下降.100 μmol/L浓度组t-BHP染毒时间-细胞存活率曲线较为平缓.MTT试验提示,30μmol/L的t-BHP染毒可以促进耳蜗毛细胞增殖,200μmol/L以上各浓度组则抑制细胞增殖.DCFH-DA探针法显示,无染毒细胞镜下无荧光(-),阳性对照为强荧光(+),30和50 μmol/L浓度组则有弱荧光(-+),100μmol/L染毒组为强明亮荧光(++),200～1000μmol/L各组荧光均较强,但随着存活率的迅速降低视野下细胞稀疏.结论 100 μmol/L的t-BHP对HEI-OC1细胞染毒12h可以在不影响细胞外形、增殖能力的前提下提高耳蜗毛细胞内ROS水平,模拟噪声引起的氧化应激.