共查询到18条相似文献,搜索用时 156 毫秒
1.
目的:观察内质网应激相关因子Bip/GRP78和CHOP/Gadd153在强噪声暴露后豚鼠耳蜗细胞的表达,探讨内质网应激在强噪声暴露后豚鼠耳蜗细胞损伤中的作用。方法:选用健康雄性白色豚鼠48只,将实验组豚鼠暴露在4kHz窄带噪声120dBSPL噪声环境中4h,噪声刺激停止后1d、4d、14d组及对照组在处死前测ABR(每组各12只)。脱氧核糖核甘酸末端转移酶介导的缺口末端标记技术(TUNEIL)检测耳蜗凋亡细胞。免疫组化及Western Blot方法检测Bip/GRP78,CHOP/Gadd153蛋白的表达。结果:实验组耳蜗Corti/s器、血管纹(stria vascularis,sv)和螺旋神经节细胞(spiral ganglion cell,SGC)存在TUNEL阳性细胞,以1d组最多,而对照组未见阳性细胞。免疫组化、Western Blot检测实验组Bip/GRP78蛋白明显高于正常组,且在1d、4d、14d都维持在比较高的水平;CHOP/Gadd153蛋白含量在噪声刺激后迅速增高,1d、4d达到高峰,14d减少。结论:强噪声暴露启动内质网应激反应,诱导Bip/GRP78表达,降低细胞损伤,同时激活CHOP/Gadd153途径启动细胞凋亡来清除受害严重的细胞,这可能是内耳细胞内源性保护机制之一。 相似文献
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目的:探讨一次性大剂量放射治疗(放疗)后豚鼠内耳螺旋神经节细胞(SGC)的损伤情况。方法:白化豚鼠40只随机分为5组,每组8只,右耳为放疗组,左耳为对照组。豚鼠右耳颞部做一次性60Co照射70Gy。分别于放疗后1、4、7、14和30d处死,行耳蜗中轴切片HE染色及免疫组织化学染色。结果:HE染色显示放疗组的SGC在放疗后不同时间点均出现萎缩,放疗后各不同时间点螺旋神经节细胞萎缩率与对照组比较差异有统计学意义(P<0.01)。放疗组SGC的Caspase3的阳性表达比对照组增强,放疗后不同时间点SGC的Caspase3光密度值与对照组比较差异有统计学意义(P<0.01)。结论:放疗可引起内耳SGC的损伤,Caspase3在SGC的表达上调可能与细胞损伤有关。 相似文献
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目的:研究N-乙酰半胱氨酸(NAC)对噪声性听力损伤的保护作用。方法:32只雄性白色豚鼠随机分成4组,每组8只。从噪声暴露前7天(7 d)开始,分别灌胃给予蒸馏水、NAC 70、NAC 100、NAC 140 mg/kg,1次/d,连续14 d。在用药第8天(d 8),各组动物在中心频率4 kHz、强度115 dB (A)的倍频程噪声暴露4 h,建立暴噪模型。测定噪声暴露前、噪声暴露后d 3、d 8、d 11各组豚鼠脑干听觉反应(ABR)的阈值。以听阈偏移反映听力受损情况,组织学检查耳蜗内外毛细胞的损伤程度,来评价NAC对豚鼠噪声性听力损伤的保护作用。结果:灌胃给予NAC 100、NAC 140 mg/kg 可在一定程度上减少噪声暴露后d 3、d 8、d 11豚鼠ABR的阈移值,减轻毛细胞的损伤。结论:NAC对噪声引起的急性和亚急性听力损伤均具有一定的保护作用。 相似文献
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目的观察不用时间点暴露于不同剂量醋酸铅后大鼠神经胶质瘤C6细胞葡萄糖调节蛋白78(glucoseregulated protein 78,GRP78)表达量的影响,探讨不同时间不同剂量铅暴露对内质网应激反应的影响。方法Wistar大鼠神经胶质瘤C6细胞培养于含醋酸铅的培养液中,分别于不同时间终止染铅,用Western印迹法检测内质网GRP78表达量。结果(1)0.2μmol/L染铅组:7和30 d GRP78蛋白表达显著增高,其余各个时间点均无显著性变化;(2)1.0μmol/L染铅组:1 d后GRP78蛋白表达量开始显著增高,染铅30 d时已达到染铅前的6.3倍;(3)2.0μmol/L染铅组:0.5 h起GRP78表达量即显著增高,染铅7 d时达到高峰,是染铅前的4.3倍,到30 d时表达量又下降为染铅前的2.6倍。结论铅可以使Wistar大鼠神经胶质瘤细胞内质网上的GRP78蛋白应激性表达增加,内质网上的GRP78是铅的重要蓄积库。 相似文献
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目的:在体外建立大鼠耳蜗螺旋神经节神经元培养模型,并提高其产出率及细胞活性。方法:将出生后5天的大鼠耳蜗螺旋神经节神经元在体外培养3-5天,用神经丝蛋白(Neurofilament protein,NFP)单克隆抗体进行免疫组化染色。结果:显示耳蜗螺旋神经节社会元在体外无血清培养条件下,可以存活并进行正常分化。结论:耳蜗螺旋神经节神经元在体外有稳定的可塑性及轴突再生修复能力。 相似文献
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iNOS在缺氧缺血新生大鼠耳蜗损伤中作用的实验研究 总被引:1,自引:0,他引:1
目的 探讨缺氧缺血(HI)耳蜗组织的损伤方式及诱导型一氧化氮合酶(iNOS)在其中的作用。方法 选择体重9~20g的健康新生7日龄Wistar大鼠30只,随机分为正常对照组、假手术组和HI 30min组、HI 6h组、HI 24h组、HI 48h组,共计6组。各实验组分别于模型制成完毕30min、6h、24h、48h后取脑干、耳蜗组织,做脑组织和耳蜗标本HE染色病理检查,测定耳蜗组织iNOS免疫组化。结果 各缺氧缺血实验组,内、外毛细胞明显变形,iNOS在耳蜗组织的表达明显增强,其中在HI 24h组的表达最强。结论 缺氧缺血可以引起新生7日龄Wistar大鼠耳蜗内、外毛细胞及血管纹等组织病理损伤。耳蜗组织在正常情况下,血管纹,毛细胞及螺旋神经节细胞均有iN0S弱阳性表达,在缺氧缺血实验组,随着缺氧缺血时间的延长,iNOS阳性表达增强. 相似文献
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目的 观察 D-半乳糖诱导的老化小鼠耳蜗中蛋白磷酸酶 1 核目标亚基(PNUTS)的表达。 方法 6 周龄清洁级昆明小鼠 20 只随机分为对照组和 D-半乳糖组, 每组 10 只。 D-半乳糖组小鼠颈背部皮下注射 D-半乳糖 800 mg/(kg·d); 对照组颈背部注射等量生理盐水, 均为每日 1 次, 连续 8 周。 造模完成后, 进行听脑干反应(ABR)测试检测小鼠听力变化; 取 2 组小鼠耳蜗, 采用 Western blot 检测 PNUTS 及 p53 蛋白表达; 免疫组织化学观察 PNUTS 蛋白在耳蜗毛细胞、螺旋神经节细胞及血管纹中的表达与分布情况。 结果 D-半乳糖组小鼠在 8、12、24 kHz 这 3 个频率下的 ABR 阈值与对照组差异均无统计学意义。 PNUTS 蛋白在小鼠耳蜗毛细胞、螺旋神经节细胞及血管纹细胞中有表达,且 D-半乳糖组小鼠耳蜗中 PNUTS 蛋白的阳性表达水平较对照组显著降低(P< 0.05);而 p53 蛋白表达水平则显著升高(P< 0.01)。 结论 PNUTS 在小鼠耳蜗中有表达, 且 D-半乳糖能够诱导老化小鼠耳蜗中 PNUTS 表达下调。 相似文献
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目的:本实验通过给视神经不全损伤模型大鼠玻璃体腔内注射外源性神经生长因子(NGF)及外源性睫状神经营养因子(CNTF),观察两种神经营养因子对视网膜神经节细胞是否具有一定的保护作用.方法:将30只Wistar大鼠随机分组,利用无创血管钳造成大鼠左眼视神经的不全损伤,右眼不予任何处理,作为正常对照组.并在造模成功后分别给予大鼠左眼玻璃体腔内注射NGF及CNTF各2μL,作为两组实验治疗组,实验对照组在相同时间给予大鼠左眼玻璃体腔内注射平衡盐溶液2μL.在大鼠视神经不全损伤后5d、10d时分别做RGC计数、光镜组织学观察及生长相关蛋白-43(growth associated pro-tein-43,GAP-43)免疫组织化学检测.结果:光镜下,伤后5d-10d光镜下观察实验组视网膜及视网膜神经节细胞均有不同程度水肿及肿胀,RGC数量明显比正常对照组下降,有明显的统计学差异(P<0.01),两组实验治疗组视网膜神经节细胞数目明显高于实验对照组,具有明显统计学差异(P<0.05).免疫组织化学染色结果,伤后5d实验组GCL层GAP-43表达均呈阳性,实验治疗组GAP-43的表达量明显高于实验对照组,具有明显统计学差异(P<0.05).10d后实验治疗组GAP-43表达量达高峰,实验对照组GAP-43表达量明显减少,具有明显统计学差异(P<0.05).结论:在视神经受损后NGF与CNTF能提高视网膜神经节细胞的存活率,延长GAP-43的表达时间并增加其表达量,对视网膜神经节细胞具有一定的保护作用. 相似文献
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Down-regulation of the endoplasmic reticulum chaperone GRP78/BiP by vomitoxin (Deoxynivalenol) 总被引:10,自引:0,他引:10
The mechanisms by which trichothecene mycotoxins cause immunological effects in leukocytes such as cytokine up-regulation, aberrant IgA production, or apoptotic cell death are not fully understood. In the present study, mRNA differential display analysis was used to evaluate changes in gene expression induced by the trichothecene vomitoxin (VT or deoxynivalenol) in a T-cell model, the murine EL-4 thymoma, that was stimulated with phorbol 12-myristate 13-acetate (PMA) and ionomycin (ION). Ten differentially expressed fragments of cDNA were isolated and sequenced and three of these were identified as the known genes GRP78/BiP, P58(IPK), and RAD17. Most notably, expression of GRP78/BiP (a 78-kDa glucose-regulated protein), a stress-response gene induced by agents or conditions that adversely affect endoplasmic reticulum (ER) function, was found to decrease in VT-exposed cells. Competitive RT-PCR analysis revealed that 250 ng/ml VT decreased GRP78/BiP mRNA expression in both unstimulated and PMA/ION-stimulated EL-4 cells at 6 and 24 h after VT treatment. Western blotting confirmed that VT (50 to 1000 ng/ml) also significantly diminished GRP/BiP protein levels in a dose-response manner in PMA/ION-stimulated cells. GRP78/BiP has been shown to play a role in regulation of protein folding and secretion, and to protect cells from apoptosis. When PMA/ION-stimulated cells were incubated with 50 to 1000 ng/ml VT for 24 h, 200-bp DNA laddering, a hallmark of apoptosis, increased in a dose-dependent manner. In addition to GRP78, mRNA expression of the cochaperone P58(IPK), which is the 58-kDa cellular inhibitor of the double-stranded RNA-regulated protein kinase (PKR), was also shown to be suppressed by VT-treatment. GRP78 and P58(IPK) are critical for maintenance of cell homeostasis and prevention of apoptosis. The down-regulation of these molecular chaperones by VT represent a novel observation and has the potential to impact immune function at multiple levels. 相似文献
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L C Chen P D Miller H F Lam J Guty M O Amdur 《Journal of toxicology and environmental health》1991,34(3):337-352
Urban air pollution in the United States is composed of a complex mixture of particles and gases. Among the most prominent products of the atmospheric pollutants are sulfur oxides and ozone. In this report, we use two exposure protocols to examine the interaction between exposure to these two pollutants. In the first exposure regimen, guinea pigs were exposed to sulfuric acid (pure sulfuric acid mist or sulfuric acid layered on ZnO) for 1 h. Each exposure is followed 2 h later by another exposure to 0.15 ppm ozone for 1 h. Pulmonary function parameters were measured immediately after the ozone exposure. In guinea pigs that were exposed to 300 micrograms/m3 pure sulfuric acid mist, subsequent exposure to 0.15 ppm ozone did not produce additional change in pulmonary functions. In guinea pigs that were exposed to 84 micrograms/m3 sulfuric acid layered on ZnO, subsequent exposure to 0.15 ppm ozone produced more than additive alterations in vital capacity and diffusing capacity. In the second exposure regimen, guinea pigs were exposed to 24 micrograms/m3 sulfuric acid layered on ZnO for 3 h/d for 5 d. On d 8 and 9, animals received two additional daily 3-h exposures to 24 micrograms/m3 sulfuric acid layered on ZnO, and pulmonary functions were measured at the end of the daily exposure. Greater reductions in lung volumes and diffusing capacity were observed in animals on d 9 than would be observed in animals that received no additional exposure. In the third exposure regimen, guinea pigs were exposed to 24 micrograms/m3 sulfuric acid layered on ZnO for 3 h/d for 5 d. On d 9, animals were exposed to 0.15 ppm ozone for 1 h and pulmonary functions were measured at the end of the ozone exposure. Ozone exposure on d 9 induced reductions in lung volumes and diffusing capacity that were not observed in animals receiving exposures to either ozone or sulfuric acid layered ZnO alone. We conclude that single or multiple exposure to sulfuric acid-layered ZnO sensitizes guinea pigs to subsequent sulfuric acid or ozone exposure. 相似文献
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目的 观察自由基清除剂α-硫辛酸对噪声性听力损伤的保护作用。方法 24只体重为250~300 g的雄性纯白色豚鼠,按体重随机分为α-硫辛酸低、中、高剂量组(n=3×6)、噪声对照组(n=6)。各组动物暴露倍频程噪声(4 kHz中心频率)115 dB SPL(sound pressure level,声压级) 4 h。α-硫辛酸组动物暴露前2 d、暴露当天至暴露后7 d连续灌胃给予α-硫辛酸30 mg/(kg·d)(低剂量组)、60 mg/(kg·d)(中剂量组)、120 mg/(kg·d)(高剂量组);对照组动物相应时间灌胃给予等量的生理盐水。暴露后不同时间(3、7、10 d)测试各组动物在不同频率(8、16、24、32 kHz)下的听觉脑干反应(auditory brainstem response,ABR)值,组织学检查内外毛细胞缺失和损伤程度,以测试时的听阈值与暴露前听阈差值(听阈偏移)反映听力受损情况。结果 暴露后3 d,低、中、高剂量组在8、16 kHz频率下,与噪声对照组相比较具有显著性差异;低、高剂量组在24、32 kHz频率下与噪声对照组相比较具有显著性差异;暴露后7 d,中、高剂量组在8、16、24 kHz频率下与噪声对照组相比较具有显著性差异;低、高剂量组在32 kHz频率下与噪声对照组相比较具有显著性差异;暴露后10 d,高剂量组与噪声对照组比较具有显著性差异。组织学检查,α-硫辛酸组动物无明显内外毛细胞缺失,毛细胞形态结构破坏较轻。对照组动物内耳外毛细胞显示水肿、空泡变性等病变。结论 高、中、低剂量的α-硫辛酸对噪声性听力损伤均有一定的预防作用;高剂量的α-硫辛酸对噪声性听力损伤具有很好的预防和治疗作用。 相似文献
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R K Wolff R F Henderson R H Gray R L Carpenter F F Hahn 《Journal of toxicology and environmental health》1986,17(1):129-142
The responses of guinea pigs and rats to inhaled sulfuric acid aerosols were compared to define species differences and to determine the small-animal model most relevant to human exposures. Rats were exposed for 6 h to 1, 10, and 100 mg H2SO4/m3. Guinea pigs were exposed for 6 h to 1, 10, and 27 mg H2SO4/m3. Tracheal mucous clearance of guinea pigs was slowed 1 d after exposures to 1 mg H2SO4/m3. A tendency toward faster clearance was observed at high concentrations of H2SO4 for both guinea pigs and rats (statistically significant only for the rats). The speeding of mucous clearance was correlated with increases in airway sialic acid and also with the appearance of excess tracheal secretions, detected using scanning electron microscopy in both rats and guinea pigs. The responses of guinea pigs to sulfuric acid exposures were more similar to those reported for humans than were those of rats. 相似文献
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R F Gerlach M A Medinsky C H Hobbs D E Bice W E Bechtold Y S Cheng N A Gillett L S Birnbaum J L Mauderly 《Journal of applied toxicology : JAT》1989,9(3):145-153
Reports of respiratory problems among industrial workers exposed repeatedly by inhalation to azodicarbonamide (ADA) raised concern that ADA might be a pulmonary sensitizer. We used a non-invasive method for measuring specific airway conductance to evaluate the potential for repeated inhalation of unconjugated ADA to cause specific or non-specific pulmonary sensitization in the guinea pig. Two groups of male Hartley guinea pigs were exposed 6 h/day, 5 days/week for 4 weeks to aerosolized ADA at 51 or 200 mg/m3, or to filtered air as controls. One group was tested for specific sensitization to ADA by measuring specific airway conductance during inhalation challenge with ADA before and on the third day after the 4-week ADA exposure. The ADA concentrations for the challenges were identical to the repeated exposure concentrations (51 or 200 mg/m3, 200 mg/m3 for controls). The other group was tested for non-specific airway sensitization by inhalation challenge with aerosolized histamine before and after the 4-week ADA exposure. Histamine was administered in stepwise increasing concentrations to elicit an airway response in each guinea pig. Skin tests for immunological responses to ADA, body weight and histopathology of the respiratory tract and skin test sites were also evaluated. The 4-week exposure to ADA did not result in either specific or non-specific airway sensitization. The ADA exposure did not induce positive skin reactions, influence body weight or cause histopathological responses. These results indicate that ADA, acting alone (i.e. not conjugated to a protein), is not a pulmonary sensitizer in the guinea pig exposed repeatedly for 4 weeks and challenged to simulate a 'Monday morning' exposure. 相似文献
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In the present study, we investigated (1) whether airway responsiveness to inhaled histamine-aerosol could be induced during 7-d exposure of guinea pigs to 4 ppm NO2 and, if so, (2) whether thromboxane A2 may be involved in such increase. Female Hartley guinea pigs were divided into 6 groups (n = 15/group). Three groups were exposed to filtered air and the other 3 groups were exposed to NO2 for 1, 3, or 7 d (24 h/d). Baseline specific airway resistance (SRaw0) did not change significantly after exposure to 4 ppm NO2 or air. Airway responsiveness was determined 1 wk before the beginning of exposure and on the day of termination of the exposure. Prior to exposure to NO2, the EC200His, the concentrations of inhaled histamine necessary to double SRawNaCl (SRaw after inhalation of 0.9% NaCl), were 1.07 +/- 0.20, 1.30 +/- 0.20, and 1.01 +/- 0.18 mM for the 3 groups later given NO2 for 1, 3, and 7 d, respectively. Following exposure to NO2 for 1, 3, or 7 d, EC200His values were 1.42 +/- 0.25, 0.66 +/- 0.10 (p < .05), and 1.05 +/- 0.22 mM, respectively. These results show that 7-d exposure to 4 ppm NO2 induced a significant increase in airway responsiveness on d 3. Exposure to air had no significant effect on the airway responsiveness. This transient hyperresponsiveness was inhibited by a specific inhibitor of thromboxane synthetase, OKY 046. These results indicated that (1) a lower concentration (4 ppm) of NO2 than that previously reported can induce transient hyperresponsiveness in guinea pigs during appropriate long-term exposure, and (2) thromboxane A2 may play an important role in this transient airway hyperresponsiveness. 相似文献
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Alexandre M. Katos Michele Conti Theodore S. Moran Thomas W. Chon Richard K. Gordon Alfred M. Sciuto 《Inhalation toxicology》2013,25(7):648-657
We investigated the toxic effects of the chemical warfare nerve agent (CWNA) soman (GD) on the respiratory dynamics of guinea pigs following microinstillation inhalation exposure. Male Hartley guinea pigs were exposed to 841 mg/m3 of GD or saline for 4 min. At 24 and 48 h post GD exposure, respiratory dynamics and functions were monitored for 75 min after 1 h of stabilization in a barometric whole-body plethysmograph. GD-exposed animals showed a significant increase in respiratory frequency (RF) at 24 h postexposure compared to saline controls. The 24-h tidal volume (TV) increased in GD-exposed animals during the last 45 min of the 75-min monitoring period in the barometric whole-body plethysmograph. Minute ventilation also increased significantly at 24 h post GD exposure. The peak inspiratory flow (PIF) increased, whereas peak expiratory flow (PEF) decreased at 24 h and was erratic following GD exposure. Animals exposed to GD showed a significant decrease in expiratory (Te) and inspiratory time (Ti). Although end inspiratory pause (EIP) and end expiratory pause (EEP) were both decreased 24 h post GD exposure, EEP was more evident. Pause (P) decreased equally during the 75-min recording in GD-exposed animals, whereas the pseudo lung resistance (Penh) decreased initially during the monitoring period but was near control levels at the end of the 75-min period. The 48-h respiratory dynamics and function parameter were lower than 24 post GD exposures. These results indicate that inhalation exposure to soman in guinea pigs alters respiratory dynamics and function at 24 and 48 h postexposure. 相似文献
18.
R V Johnston M N Pinkerton D C Mensik L D Swaim V A Linscombe M C Benge G Barna-Lloyd D J Kilian 《Journal of toxicology and environmental health》1979,5(6):1025-1035
Four groups of 4 domestic pigs were exposed to 0, 20, 100, and 500 ppm benzene vapor 6 h/d, 5 d/wk, for 3 wk. Two groups of 10 rats were exposed to 0 and 500 ppm: the exposed rats for 6 h/d, 5 d/wk, for 3 wk, the nonexposed rats for 6 h/d, 5 d. Rats were killed within 72 h after exposure; values for pigs were obtained shortly after exposure and on final examination at 4-16 wk after exposure. Pigs were evaluated for changes in white and red blood cell counts, hemoglobin level, lymphocyte count, proportion of E-rosette-forming lymphocytes, myeloid-erythroid ratio, and presence of multinucleate erythroblasts. With the exception of the E-rosette test, the same parameters were measured in the rat. Statistically significant (p less than 0.05) depression of white cell counts, total lymphocytes, and proportion of E-rosette-forming lymphocytes was observed in pigs exposed to 500 ppm; recovery to values not significantly different from control values was observed on final examination. Fewer postexposure effects were seen at 100 ppm, and there were no significant differences from control values at 20 ppm. Both pigs and rats exposed to 500 ppm showed a significant decrease in the mean myeloid-erythroid ratio within 72 h. These values returned to normal in the pig 4-16 wk after exposure; recovery in the rat was not evaluated. An increased number of bone marrow erythroblasts with more than 2 nuclei was found on final examination of pigs exposed to 500 and 100 ppm, but the difference was significant only at the 100-ppm level because of the variability at the higher level. A significant increase (p less than 0.004) in multinucleate cells was seen in the rats exposed to 500 ppm. 相似文献