内质网应激在老年大鼠耳蜗细胞凋亡中的作用

目的探讨内质网应激在老年大鼠耳蜗细胞凋亡中的作用,从而进一步探索老年性聋的发病机制。方法Wistar大鼠24只,其中12只为对照组(3～4月龄),12只为自然衰老组(22～24月龄);比色法测定内耳组织中超氧化物歧化酶(superoxide dismutase,SOD),丙二醛(malondialchehyche,MDA)水平;ABR检测听力学改变;免疫组化及western blot检测GRP78/BiP和Caspase-12蛋白的表达。结果老年大鼠听力下降;内耳组织SOD活性降低,MDA升高,与对照组相比差异有统计学意义(P<0.05);耳蜗切片中及western blot结果可见GRP78的表达与对照组相比差异无统计学意义(P<0.05);caspase-12的表达明显高于对照组,差异有统计学意义(P<0.05)。结论内质网凋亡途径是老年大鼠老年性聋的发生机制之一。     

幼年及成年豚鼠的耳蜗组织学观察

采用不同年龄组豚鼠随机分甲、乙两组.甲组按年龄3、6、12个月龄分为甲_1、甲_2、甲_3组(统称自然衰老组);而乙组仅取3个月龄的豚鼠(下称人工促衰老组),于眼球后注射促衰老制剂持续32天.各组行测听(ABR)后处死,测其心、脑中的丙二醛(Malondialdehyed,MDA)及超氧化物歧化酶(Superoxide dismutase,SOD)活力并于扫描电镜下行内耳组织学观察.结果表明12个月龄豚鼠内耳组织学呈现自然衰老典型改变,且ABR、MDA、SOD各指标均与老年各指标的改变相一致;3个月龄人工促衰老组无论在内耳组织学的改变及ABR、MDA、SOD与12个月龄豚鼠相比亦基本一致.表明采用豚鼠制作模型以研究老年性聋是可行的.     

川芎嗪激活Keap1/Nrf2通路抗顺铂致聋模型大鼠氧化应激损伤的作用研究

目的 探讨川芎嗪基于Keap1/Nrf2通路对顺铂致聋模型大鼠氧化应激损伤的作用及机制。方法 80只Wistar大鼠随机均分为空白组(B组)与模型组(M组),M组大鼠腹腔注射顺铂4 mg·kg^-1·d^-1构建药物性聋模型后，将B组与M组各自再随机均分为2组，分别是：空白对照组(BC组),空白+川芎嗪组(BC+TMP组),模型对照组(MC组),模型+川芎嗪组(MC+TMP组)。BC+TMP组和MC+TMP组腹腔注射川芎嗪140 mg·kg^-1·d^-1,BC组和MC组腹腔注射等量生理盐水，均每日1次，连续2周。行ABR检测后用比色法检测各组大鼠血清中丙二醛(MDA)和超氧化物歧化酶(SOD),运用蛋白质印迹法检测各组大鼠耳蜗组织中Keap1、Nrf2、p-Nrf2的蛋白表达水平，运用免疫荧光双标技术检测各组大鼠耳蜗组织中Keap1、Nrf2、Keap1/Nrf2共表达水平。结果 M组大鼠ABR阈值明显高于B组(P<0.05),M组大鼠耳蜗毛细胞出现大量溶解破坏等病理改变；MC+TMP组ABR阈值低...     

川芎嗪对顺铂耳聋大鼠耳蜗Fas/Fas L及caspase8的调控研究

观察川芎嗪对顺铂诱导的耳聋模型大鼠耳蜗毛细胞的抗凋亡作用,并探索其抗凋亡的部分作用机制。方法 120只SPF级Wistar分为4组,正常对照组;正常+川芎嗪组;模型对照组;模型加川芎嗪组。采用顺铂腹腔注射的方法诱导药物性耳聋大鼠模型,通过川芎嗪腹腔注射对顺铂耳聋模型大鼠进行干预,采用听觉脑干诱发电位ABR阈值的检测及大鼠耳蜗基底膜铺片的方法对模型进行评价,并对各组大鼠耳蜗组织中Fas、Fas L和caspase-8 m RNA及蛋白表达水平进行检测。结果模型对照组大鼠ABR阈值明显高于正常对照组,川芎嗪具有一定的降低顺铂耳聋模型大鼠ABR阈值的作用;顺铂耳聋模型大鼠耳蜗毛细胞明显溶解缺失、排列紊乱等病理改变;模型对照组大鼠耳蜗组织中Fas、Fas L和caspase-8 m RNA及蛋白表达水均显著高于正常对照组,经川芎嗪腹腔注射干预后,三者表达水平得到了一定的控制。结论顺铂可诱导药物性耳聋大鼠模型,川芎嗪对耳聋模型大鼠具有一定的干预作用;顺铂腹腔注射可导致大鼠耳蜗组织中Fas、Fas L和caspase-8 m RNA及蛋白表达水平,而川芎嗪注射液可能是通过抑制Fas、Fas L和caspase-8 m RNA及蛋白的表达水平而实现其抗凋亡作用。     

银杏叶提取物对噪声致大鼠螺旋神经节损伤的保护作用

目的探讨银杏叶提取物对大鼠噪声暴露后螺旋神经节损伤的保护作用。方法将36只SD大鼠分为三组：正常对照组（正常组）、生理盐水＋噪声暴露组（噪声组）、银杏叶提取物＋噪声暴露组（用药组）,每组12只。后两组大鼠每天暴露于110dBSPL白噪声中6h,连续10天,且于噪声暴露开始每天分别腹腔注射生理盐水和银杏叶提取物10ml/d。所有大鼠均于实验前和实验第10天检测听性脑干反应（auditory brainstem response,ABR）,并于第二次测试ABR后处死动物,检测耳蜗组织超氧化物歧化酶（SOD）活性、丙二醛（MDA）含量,并用透射电镜观察耳蜗螺旋神经节细胞的超微结构变化。结果实验后噪声组和用药组的ABR阈值均高于正常组,但用药组显著低于噪声组,差异有统计学意义;用药组SOD活性较噪声组明显增加、MDA含量较噪声组显著降低,差异有统计学意义;用药组耳蜗螺旋神经节损害明显轻于噪声组。结论银杏叶提取物对大鼠噪声暴露后螺旋神经节细胞的损害具有保护作用。     

iNOS在链霉素耳中毒豚鼠耳蜗血管纹的表达

目的探讨链霉素（streptomycin,SM）耳中毒过程中豚鼠耳蜗诱生型一氧化氮合霉（inducible nitric oxide synthase,iNOS）的表达.方法 20只豚鼠随机分为正常对照组、SM组,每组10只,SM组每日腹腔注射硫酸链霉素150 mg/kg,正常对照组每日腹腔注射等量生理盐水,用药10天后处死.以听性脑干反应（ABR）为监测指标,结合电镜、免疫组化及图像分析技术,检测链霉素耳中毒过程中耳蜗血管纹iNOS的表达及形态学改变.结果用药10天后,SM组ABR阈值明显高于正常对照组,有统计学差异（P〈0.01）,电镜下可见SM组血管纹损伤严重;免疫组化结果表明,SM组血管纹iNOS的表达明显高于正常对照组.结论 SM耳中毒时ABR阈值升高,血管纹iNOS表达增强.     

外源性谷氨酸对大鼠耳蜗核的毒性损伤实验研究

目的建立一种立体定位注射谷氨酸损伤大鼠耳蜗核的动物模型并观察其损伤特点。方法采用脑立体定位技术向成年Wistar大鼠右侧耳蜗核注射10mmol/L的谷氨酸2μl,左侧耳蜗核注射等量生理盐水,术后不同时间进行听性脑干反应测试,并用免疫组化方法观察耳蜗核的神经元和神经胶质细胞变化。结果术前大鼠ABR阈值平均22.23±3.04dBSPL,手术后ABR阈值右侧平均58.24±22.13dBSPL,左侧59.28±22.30dBSPL,较术前明显升高(P<0.01)。术后第7d,ABR阈值右侧平均49.42±25.17dBSPL,左侧平均45.19±22.45dBSPL,术后10d,ABR阈值右侧平均43.27±17.16dBSPL,左侧平均38.32±16.20dBSPL,右侧与左侧比较差异无显著统计学意义(P>0.05)。耳蜗核免疫组化结果证实注射点神经元减少,局部形成空腔及坏死灶,神经胶质细胞在坏死灶周围增生,右侧损伤较左侧明显。结论立体定位注射技术可以建立大鼠耳蜗核的损伤模型,谷氨酸可以加重其听力损伤。听力损失在术后有自恢复的趋势。     

弥漫性脑外伤大鼠听功能及耳蜗形态学改变的实验研究北大核心CSCD

目的观察弥漫性脑外伤(diffuse brain injury,DBI)大鼠听功能和耳蜗形态学的变化。方法 SD大鼠150只,随机分为正常对照组和DBI后1、2、3、4周组,每组30只。对照组不作任何处理,其他4组制作大鼠DBI模型,造模成功后,分别对各组大鼠进行ABR、40Hz AERP、ASSR测试,并以光镜、电镜观察各组大鼠耳蜗形态学变化。结果 DBI后1周组的ABR、40Hz AERP、ASSR阈值较正常组升高,第2、3周组阈值升高更明显,而在第4周组阈值略降低,DBI各组间及各组与对照组间比较差异均有统计学意义(均P<0.05)。电镜观察发现DBI 1周组耳蜗外毛细胞纤毛倒伏,线粒体嵴断裂或呈空泡变性;DBI 2、3周组外毛细胞纤毛倒伏明显,内线粒体空泡变性明显,而DBI 4周组耳蜗损伤改变减轻。结论弥漫性脑外伤可造成听功能受损及耳蜗超微结构损伤性变化。     

川芎嗪对卡那霉素耳中毒抗氧化作用的研究

通过检测豚鼠耳蜗组织超氧化物歧化酶（SOD）活力、丙二醛（MDA）含量、听神经复合动作电位（CAP）及扫描电镜观察，评价川芎嗪对卡那霉素（KM）耳中毒的抗氧化作用。结果显示：KM能 明显增加SOD活力、MDA含量及CAP阈值。同时应用KM和川芎嗪后，与KM组对比，听力有改善，SOD活力、MDA含量显著下降；与正常组相比，SOD、MDA无明显变化，听力轻度下降。推测脂质过氧化反应参与了KM耳中毒的过程。并探讨了川芎嗪对KM耳中毒抗氧化作用的可能机制。     

连翘酯苷对顺铂耳毒性防护作用的实验研究

目的观察连翘酯苷对顺铂耳毒性的防护作用并探讨其机制。方法将42只听力正常豚鼠随机分为空白组(10只):腹腔注射生理盐水8.0 ml·kg-1·d-1,连续8天;顺铂组(16只):腹腔注射顺铂2.0 mg·kg-1·d-1,连续8天;拮抗组(16只):前2天腹腔注射连翘酯苷25.0 mg·kg-1·d-1,第3天起腹腔注射连翘酯苷后30 min,再腹腔注射顺铂2.0 mg·kg-1·d-1,连续8天。每组豚鼠首次用药前及末次用药后第二天均行ABR检测,末次检测完毕后,心脏穿刺采血检测血清总超氧化物歧化酶(total superoxide disumutase,T-SOD)活性和丙二醛(malondialdehyde,MDA)含量,最后断头处死并取耳蜗,行硝酸银染色全耳蜗铺片、耳蜗组织切片和扫描电镜观察。结果空白组、顺铂组、拮抗组用药后ABR阈值分别为7.57±4.59、41.65±6.56、30.63±5.02 dB nHL;血清T-SOD活性分别为186.18±23.46、82.61±36.12、123.53±30.76 U/ml;MDA含量分别为4.14±0.79、10.69±1.21、7.85±0.97 nmol/ml。拮抗组ABR阈值低于顺铂组(P<0.05),顺铂组血清中T-SOD活性最低,而MDA含量最高,差异有统计学意义(P<0.5)。顺铂组耳蜗外毛细胞缺失明显,平均缺失率为53.42%,毛细胞结构紊乱,血管纹紊乱、螺旋神经节细胞数减少,而拮抗组这些损害明显减轻。结论连翘酯苷在一定程度上可以防护顺铂所致的耳蜗损伤,机制可能与其清除耳蜗组织氧自由基、减少氧化应激反应有关。     

L-精氨酸对肾性高血压大鼠畸变产物耳声发射的影响

目的：观察L-精氨酸（L—Arg）对。肾性高血压大鼠畸变产物耳声发射（DPOAE）的影响。方法：将二肾一夹（2K1C）型肾血管型高血压模型的大鼠24只分成模型对照组和L-Arg治疗组各12只；另设正常对照组12只。动物处死前检测DPOAE，并测定耳蜗组织超氧化物歧化酶（SOD）、丙二醛（MDA）和血浆内皮素（ET）的含量。结果：①与正常对照组比较，模型对照组SBP和血浆ET含量明显升高（分别P〈0．01和P〈0．05）；耳蜗组织MDA平均含量明显升高（P〈0．01）；SOD活力明显下降（P〈0．05）。在70dBSPL的高刺激强度下，3组各频率的DPOAE检出率均为100％；在低刺激强度（49dBSPL）下，模型对照组检出率明显降低，与正常对照组比较在各频率DPOAE检出率差异有统计学意义（P〈0．05或P〈0．01）。模型对照组在各频率DPOAE幅值均有所下降，与正常对照组比较差异有统计学意义（P〈0．05或P〈0．01）。②L—Arg治疗组与模型对照组比较，SBP和血浆ET含量均明显降低（均P〈0．01）；SOD活力明显高于模型对照组（P〈0．05）；耳蜗组织MDA平均含量明显低于模型对照组（P〈0．01）。在低刺激强度（49dBSPL）下，L—Arg治疗组在各频率DPOAE检出率与模型对照组比较差异有统计学意义（P〈0．05或P〈0．01）；DPOAE幅值在各频率与模型对照组比较均有所提高（P〈0．05或P〈0．01），而DPOAE潜伏期差异无统计学意义（P〉0．05）。③L-Arg治疗组与正常对照组相比，上述各指标均无统计学意义（均P〉0．05）。结论：①L—Arg可能通过改变大鼠内耳微循环而影响肾性高血压大鼠DPOAE；②L—Arg可以影响耳蜗组织自由基的代谢，并有利于氧自由基的清除，L-Arg对耳蜗组织氧自由基的清除并不改变其对DPOAE的影响。     

Increased expression of inducible nitric oxide synthase in nasal mucosae of guinea pigs with induced allergic rhinitis

BACKGROUND: Nitric oxide (NO) is produced by the action of NO synthase (NOS) isoforms and is considered an important mediator of inflammatory response including airways. In this study, the changes in the expression levels of NOS isoforms in nasal mucosae were determined in a guinea pig model of allergic rhinitis. METHODS: An allergic rhinitis model was prepared in guinea pigs by repeated challenge with aerosolized dinitrophenylated ovalbumin antigen. Twenty-four hours after the last antigen challenge, the expression levels of NOS isoforms in nasal mucosae were determined by immunoblottings. Changes in the isometrical tension of isolated mucosal tissues of nasal septa induced by histamine were measured also. RESULTS: Although the expression levels of endothelial NOS (eNOS) and neuronal NOS (nNOS) in nasal mucosae were not affected by the repeated antigen exposure, the inducible NOS (iNOS) level was markedly and significantly increased in the challenged animals. In isolated nasal mucosal tissues, histamine induced a concentration-dependent relaxation, which was sensitive to an H1-receptor antagonist, mepyramine, and an NOS inhibitor, L-NMMA. No significant change in the histamine responsiveness was observed between the sensitized control and repeatedly antigen-challenged groups. CONCLUSION: The expression of three isoforms of NOS, including eNOS, nNOS, and iNOS, was presented in guinea pig nasal mucosa. A marked increase in iNOS expression in the repeatedly antigen-challenged animals suggests an important role of iNOS in the pathogenesis of allergic rhinitis. However, the pathophysiological role(s) of NO generated by iNOS in nasal allergy is still unclear.     

变应性鼻炎患者血清氧化应激状态研究

目的 检测变应性鼻炎(allergic rhinitis,AR)患者外周血血清中氧化应激标志物,探讨氧化应激反应在AR发病机制中的作用.方法 留取23例健康人、48例AR患者外周血血清,分别检测氧化应激标志物一氧化氮(nitric oxide,NO)、诱导型一氧化氮合酶(inducible nitric oxide synthase,iNOS)、总一氧化氮合酶(total nitric oxide synthase,TNOS),脂质过氧化产物丙二醛(malondidehyde,MDA),以及体内主要抗氧化酶超氧化物歧化酶(superoxide dismutase,SOD)、谷胱甘肽过氧化物酶(glutathione peroxidase,GSH-Px)水平.采用SPSS 13.0软件对数据进行分析.结果 AR患者血清NO水平((x)±s,以下同)为[(97.92±73.42)μmol/L]较健康对照组[(64.04±29.54)μmol/L]明显升高(t=-0.281,P<0.05);iNOS与TNOS比值(0.51±0.11)较健康对照组(0.45±0.15)明显升高(t=-2.061,P<0.05);血清GSH-Px活性[(258.24±45.25)U/(ml·min)]较健康对照组[(215.11±47.62)U/(ml·min)]明显升高(t=-2.2349,P<0.05)).而AR患者血清SOD活性、MDA含量较健康对照组分别有升高和降低趋势,但差异无统计学意义(Z=-1.656,t=1.922,P值均>0.05).结论 氧化应激反应参与AR病理生理过程,而iNOS-NO通路在AR的发病过程中可能发挥着更为重要的作用.     

Pattern of hearing loss in a rat model of cochlear implantation trauma.

HYPOTHESIS: Trauma caused by cochlear implant electrode insertion is attributable to the combination of direct physical trauma and the delayed cell death of oxidative stress-injured auditory sensory cells. BACKGROUND: Histologic evaluation of cochlear implant electrode trauma has demonstrated that the extent of sensory cell losses is proportional to the degree of injury. However, the impact of delayed oxidative stress within injured cochlear tissues and the progressive loss of injured hair cells by way of apoptosis are at present unknown. METHODS: Laboratory rats were evaluated for hearing acuity before and after electrode insertion, before and after round window membrane incision only. Hearing was measured before trauma or incision and over the next 7 days. Objective measurements of hearing function were distortion products of otoacoustic emissions (DPOAEs) in the frequency range of 2 to 32 kHz and tone-burst (i.e., 4-32 kHz) evoked auditory brain stem responses (ABRs). RESULTS: For the experimental cochleae, there were progressive increases in ABR thresholds and decreases in ABR amplitudes. The amplitude of the DPOAEs in the experimental cochleae also showed progressive decreases. For the contralateral control and round window membrane surgical control ears, there were no significant changes in either DPOAE or ABR thresholds. CONCLUSION: These results document a progressive loss of hearing acuity postimplantation and strongly suggest that electrode insertion trauma generated oxidative stress within injured cochlear tissues.     

c-myc在大鼠耳蜗组织发育和耳蜗前体细胞分化过程中的表达变化

目的 通过检测c-myc基因在大鼠耳蜗组织发育及前体细胞分化过程中的表达情况,探讨其在哺乳动物耳蜗发育中的作用.方法 ①取E10、E15、P1、P7和P14的SD大鼠耳蜗组织,应用RT-PCR、Western blot的方法检测c-myc在大鼠耳蜗组织发育过程中的表达情况.②取耳蜗前体细胞和分化7天后的分化细胞,用RT-PCR、免疫细胞化学染色和Western blot的方法检测c-myc在耳蜗前体细胞分化过程中的表达情况.结果 从胚胎至出生后的耳蜗发育过程中,c-myc表达量呈现逐渐下降趋势;在前体细胞的分化过程中,c-myc的表达量也呈现下降趋势.结论 c-myc可能参与调控大鼠耳蜗组织的发育及前体细胞的分化.     

Effect of protective agents against cisplatin ototoxicity

HYPOTHESIS: The goals of this investigation were to compare the efficacy of three protective agents against cisplatin-induced elevation of auditory brainstem response (ABR) thresholds and to examine whether these protective agents prevent cisplatin-induced alterations of the antioxidant defense system in the cochlea of the rat. BACKGROUND: Cisplatin is an ototoxic antitumor agent. Previous animal studies have shown that cisplatin administration causes an elevation of ABR thresholds. These auditory changes are accompanied by alterations in the concentration of glutathione and the antioxidant enzymes in the cochlea. The authors' previous work has indicated that the protective agent diethyldithiocarbamate (DDTC) prevents decrease in glutathione (GSH), alteration of antioxidant enzyme activity, and disruption of cochlear function with cisplatin administration. METHODS: Wistar rats were sedated and underwent pretreatment ABR testing using clicks and tone burst stimuli at 8, 16, and 32 kHz. Control rats received saline by intraperitoneal (i.p.) injection. Positive control rats were administered cisplatin 16 mg/kg i.p. Three groups of rats received protective agents in combination with cisplatin. The DDTC-protected rats were given 600 mg/kg of DDTC subcutaneously 1 hour after cisplatin. Animals protected by 4-methylthiobenzoic acid (MTBA) were given 250 mg/kg of this agent i.p. 30 minutes before cisplatin. Animals protected with ebselen were given 16 mg/kg i.p. one hour before cisplatin. The ABR thresholds were recorded 72 hours after cisplatin administration in all groups. Cochleas were removed, and extracts of the tissues were analyzed for GSH, activities of antioxidant enzymes (superoxide dismutase [SOD], catalase, glutathione peroxidase, and glutathione reductase) and malondialdehyde (MDA) (as an index of lipid peroxidation). RESULTS: Cisplatin-treated rats had significant ABR threshold shifts, ranging from 27 to 40 dB. Rats administered each of the three protective agents in combination with cisplatin had ABR threshold shifts of <10 dB. The cochleae of rats administered cisplatin alone had nearly a 50% depletion of glutathione and about a 50% reduction in the activities of SOD, glutathione peroxidase, and glutathione reductase, while catalase activity was reduced to 70% of control values. These changes were accompanied by a reciprocal elevation of MDA of 165%. These changes, namely, the depletion of GSH and antioxidant enzyme activity and the elevation of MDA in the cochlea, were largely attenuated by the administration of the protective agents tested. CONCLUSION: These findings suggest that cisplatin ototoxicity is related to lipid peroxidation and that the use of protective agents prevents hearing loss and lipid peroxidation by sparing the antioxidant system in the cochlea. These results suggest the possibility that the clinical use of protective agents could effectively reduce or prevent damage to the inner ear of patients receiving cisplatin chemotherapy, provided that the antitumor effect is not altered.     

甲磺酸去铁胺抗庆大霉素耳毒性作用及机理研究

目的探讨铁螯合剂甲磺酸去铁胺（ｄｅｆｅｒｏｘａｍｉｎｅｍｅｓｙｌａｔｅ,ＤＦＯ）对抗庆大霉素（ｇｅｎｔａｍｉｃｉｎ,ＧＭ）耳毒性作用及其机理。方法豚鼠随机分为ＧＭ组（１７只）、ＤＦＯ组（８只）、ＧＭ＋ＤＦＯ组（１７只）及对照组（８只）,采用听性脑干反应（ａｃｏｕｓｔｉｃｂｒａｉｎｓｔｅｍｒｅｓｐｏｎｓｅ,ＡＢＲ）、耳蜗铺片及透射电镜技术,观察用药前后听反应阈及形态学变化,检测血清尿素氮、肌苷以及ＧＭ浓度,同时测定耳蜗和肾皮质组织中丙二醛、超氧化物歧化酶和铁离子含量。结果ＧＭ组８ｋＨｚＡＢＲ阈移为４０～６０ｄＢ;ＧＭ＋ＤＦＯ组阈移为１５～２５ｄＢ,差异有显著性（Ｐ＜０．０５）。形态学改变与听力变化一致。ＤＦＯ对ＧＭ血药浓度没有影响。ＧＭ组肾功明显损伤,但肾皮质丙二醛、超氧化物歧化酶和铁离子变化差异无显著性（Ｐ＞０．０５）,ＧＭ＋ＤＦＯ组耳蜗组织丙二醛和铁离子含量较ＧＭ组明显减少（Ｐ＜０．０５）,超氧化物歧化酶含量明显高于ＧＭ组（Ｐ＜０．０５）。结论自由基和铁离子在ＧＭ的耳毒性中起重要作用,ＤＦＯ能有效减轻ＧＭ的耳毒性作用,可能成为有希望的预防药物。     

甲磺酸去铁胺抗庆大霉素耳毒性作用及机理研究

目的 探讨铁螯合剂甲磺酸去铁胺对抗庆大霉素耳毒性作用及其机理。方法 豚发为ＧＭ组（１７只）、ＤＦＯ组（８只）、ＧＭ＋ＤＦＯ组（１７只）及对照组（８只）,采用听性脑干反应,耳蜗铺片及透射电镜技术,观察用药前后听反应阈及形态学变化,检测血清尿素氮、革以及ＧＭ浓度,同时测定耳蜗和肾皮质组织中丙二醛、超氧化物歧化酶和铁离子含量。结果 ＧＭ组８ｋＨｚＡＢＲ阈移为４－６０ｄＢ;ＧＭ＋ＤＦＯ组阈移为１５－２５ｄ     

离体豚鼠耳蜗灌流一氧化氮供体对耳蜗组织中环磷酸鸟苷含量的影响

目的 通过对离体的豚鼠耳蜗即刻灌流一氧化氮供体（DEA－NO）及可溶性鸟苷酸环化酶（sGC)抑制剂（ODQ），来改变耳蜗组织中环磷酸鸟苷（cGMP）含量，以便进一步研究一氧化氮／环磷酸鸟苷（NO／cGMP)途径在耳蜗中的调节作用。方法 24只纯种白色雄性豚鼠完全随机分为三组，分别灌流人工外淋巴基础液、DEA－NO／人工外淋巴基础溶液、ODQ＋DEA－NO／人工外淋巴基础溶液，收集耳蜗组织标本；用放射免疫的方法测定耳蜗组织中cGMP的含量。结果 向离体耳蜗中灌注1mM DEA-NO溶液可以引起耳蜗组织中cGMP含量的显著增加，先灌注ODQ，后灌注1mM DEA-NO，耳蜗组织中cGMP合成量明显少于单独灌注1mM DEA-NO，但仍高于对照组。结论 对离体的豚鼠耳蜗即刻灌流一氧化氮供体（DEA－NO）及可溶性鸟苷酸环化酶（sGC)抑制剂（ODQ），可以作用于NO／cGMP途径，改变耳蜗组织中cGMP含量，同时用放射免疫测定耳蜗组织中cGMP含量的方法是可行的。     

Ischemia-reperfusion injury of the cochlea: effects of an iron chelator and nitric oxide synthase inhibitors

Release of free iron from cellular stores and activation of nitric oxide synthase (NOS) has been implicated in a wide variety of cochlear injuries. In order to evaluate the effects of deferoxamine (a iron chelator), 3-bromo-7-nitroindazole (a relatively selective neuronal NOS (nNOS) inhibitor) or aminoguanidine (a relatively selective inducible NOS (iNOS) inhibitor) on the post-ischemic cochlear dysfunction, albino guinea pigs were subjected to 30 min ischemia, and the threshold shifts of the compound action potential (CAP) from pre-ischemic values were compared with those of control animals 4 h after the onset of reperfusion. A statistically significant reduction in the post-ischemic CAP threshold shift was observed in the animals treated with deferoxamine or 3-bromo-7-nitroindazole. However, aminoguanidine did not affect the post-ischemic CAP threshold shift. These results suggest that free iron and nNOS play deleterious roles in the cochlear injury induced by transient ischemia.