成纤维细胞生长因子耳蜗内灌注防治爆震性聋的实验研究

选用豚鼠１９只，震前于圆窗龛放银球电极测复合动作电位（ＣＡＰ）反应阈，爆震后测ＣＡＰ，于耳蜗底回打孔，分别灌注酸性成纤维细胞生长因子（ａＦＧＦ）和碱性成纤维细胞生长因子（ｂＦＧＦ），４８小时后再测ＣＡＰ，处死动物做耳蜗琥珀酸脱氢酶（ＳＤＨ）组化染色铺片。结果爆震后灌注ｂＦＧＦ、ａＦＧＦ两组动物４８小时ＣＡＰ平均阈值分别为８８．７ｄＢ和９３．２ｄＢ，而单纯打孔组和灌注外淋巴组ＣＡＰ平均阈值分别为１１９．４ｄＢ和１０７．５ｄＢ，差异有显著性（Ｐ＜０．０５和０．０１）。铺片结果示灌流生长因子两组动物耳蜗毛细胞损伤程度比其他两组要轻。结果提示ｂＦＧＦ、ａＦＧＦ耳蜗内灌注对爆震性聋ＣＡＰ反应阈恢复有促进作用，在耳蜗声损伤过程中有保护和修复功用。     

碱性成纤维细胞生长因子肌肉注射防治爆震性聋的实验观察

目的 为验证碱性成纤维细胞生长因子（ｂＦＧＦ）对爆震性耳聋 防治作用。方法 选用２豚鼠３５只,分为４组：ｂＦＧＦ肌注治疗组（１０只）,震后即刻给予ｂＦＧＦ肌注（５０ＩＵ／１００ｇ）连用４周,生理盐水肌注治疗组（１０只）,疗程同前;ｂＦＧＦ肌注预防组（１０只）,生理盐水肌注预防组（５只）,剂量同治疗组连用２周。动物爆震１００发,每秒１发,脉宽０．５ｍｓ,压力峰值１７２．０ｄＢＳＰＬ,爆震前后测定ＡＢ     

碱性成纤维细胞生长因子对耳蜗螺旋神经节细胞谷氨酸钠 …

OBJECTIVE: To understand the effects of basic fibroblast growth factor (bFGF) on survival and neurogenesis of the cultured spiral ganglion cell (SGC) of mouse after exposed to glutamate, and the effects of hFGF and glutamate on free intracellular calcium ion concentration. METHODS: After exposed to 2 x 10(-2) mol/L glutamate for 2 hours, the medium of SGC was replaced with the media containing 25, 50, 100 micrograms/L bFGF. Medium without bFGF was used as control. RESULTS: Twenty-four hours later, more cells in the control group showed signs of cell death than in bFGF groups. After 14 days, specimens were fixed in 4% paraformaldehyde and stained with toluidine blue. It was shown that the SGC in medium with bFGF exhibited more survival and longer neurites, and the effect was dose dependent (P < 0.01). Application of glutamate to the medium induced an increase to the the free intracellular calcium ion concentration in SGC, but bFGF had no such effect. CONCLUSION: Glutamate excitotoxicity was associated with free intracellular calcium ion concentration elevation in SGC, and bFGF could protect SGC against glutamate neurotoxicity.     

碱性成纤维细胞生长因子对耳蜗螺旋神经节细胞谷氨酸钠毒性作用的影响

目的了解谷氨酸钠致单离培养的小鼠耳蜗螺旋神经节细胞损伤后，碱性成纤维细胞生长因子（ｂＦＧＦ）对其生存及生长的影响，以及二者对细胞内游离钙离子浓度的影响。方法在培养液中加入２×１０２ｍｏｌ／Ｌ的谷氨酸钠２小时后，实验组分别换成含ｂＦＧＦ２５、５０、１００μｇ／Ｌ的培养液，对照组加空白培养液。结果２４小时后可见部分细胞裂解、死亡，对照组明显多于实验组。培养１４天后甲苯胺蓝染色证实，实验组的细胞生存数及细胞突起长度明显高于对照组，差异有显著性（Ｆ检验，Ｐ＜０．０１），且随着ｂＦＧＦ浓度增加，细胞生存数及细胞突起长度均增加，不同浓度实验组间差异有显著性（Ｐ＜０．０１）。用Ｆｌｕｏ３染色，激光扫描共聚焦显微镜观察１０个螺旋神经节细胞，培养液中加入谷氨酸钠后细胞内钙离子浓度迅速上升，在１０～１５秒内达峰值，１００秒左右恢复到正常水平；加入ｂＦＧＦ后细胞内钙离子浓度无明显变化（ｔ检验，Ｐ＝０．２０４）。结论谷氨酸钠可致螺旋神经节细胞内钙离子浓度升高，ｂＦＧＦ可以降低谷氨酸钠对螺旋神经节细胞的细胞毒性。     

碱性成纤维细胞生长因子鼓室给药治疗感音神经性聋的研究

目的:探讨碱性成纤维细胞生长因子治疗感音神经性聋的临床应用价值及鼓室局部给药的可行性。方法:随机选择本院1998～1999年收治的感音神经性聋患者40例(50耳),碱性成纤维细胞生长因子(bFGF)作鼓膜穿刺鼓室内给药。治疗前后进行纯音测听,定期随访,追踪观察bFGF的疗效。结果:经bFGF治疗后,患者语频、高频及0.25～4 kHz各频率的听阈平均值均有明显提高,分别与治疗前比较,差异有极显著性意义(P<0.01)。总有效率为96％,其中治愈率8％,显效率38％,好转率50％。除有轻度胀痛外,无其他不良反应。结论:鼓室局部应用bFGF治疗感音神经性聋疗效明显,方法可行。     

经大鼠圆窗膜bFGF基因转导防治爆震性聋的实验研究

目的以阳离子脂质体介导bFGF(basic fibroblast growth factor,碱性成纤维细胞生长因子)基因,经完整圆窗膜途径转染爆震后的大鼠耳蜗,观察bFGF的表达及其对爆震性聋的防治作用。方法 SD大鼠30只,随机分为四组:空白对照组(n=6),仅接受155dB SPL脉冲噪声暴露20次;EGFP(enhanced green fluorescent protein,增强型绿色荧光蛋白)对照组(n=8),噪声暴露后即刻导入EGFP/阳离子脂质体复合物;bFGF治疗组(n=8),噪声暴露后即刻导入EGFP-bFGF/阳离子脂质体复合物;bFGF保护组(n=8),噪声暴露前3天导入EGFP-bFGF/阳离子脂质体复合物。各组动物分别于噪声暴露前及噪声暴露后1天、3天、7天、14天行ABR阈值测试。噪声暴露后14天耳蜗取材做基底膜铺片,荧光显微镜观察,并做bFGF免疫荧光染色验证bFGF的表达。结果爆震后1天,bFGF保护组ABR阈值低于空白对照组及EGFP对照组,且差异均有显著性意义(P<0.05)。爆震后3天、7天和14天,bFGF治疗组及bFGF保护组ABR阈值均低于两个对照组,且差异有显著性意义(P<0.05)。而爆震前及爆震后bFGF治疗组和bFGF保护组间的ABR阈值差异均无显著性意义(P>0.05)。术后14天,荧光显微镜直接观察及bFGF免疫荧光染色均检测到毛细胞内有bFGF的定位表达。结论将阳离子脂质体介导的bFGF基因经圆窗膜导入大鼠耳蜗能够表达,表达产生的bFGF对爆震所致的耳蜗损害有一定的保护作用,它能够减轻爆震后听。     

125I标记碱性成纤维细胞生长因子脑脊液途径用药在豚鼠耳蜗分布及影响

目的 探讨碱性成纤维细胞生长因子(basic fibroblast growth factor，bFGF)进入内耳的途径及其在病理条件下对耳蜗及神经组织的保护作用机制。方法 将^125I标记bFGF(^125I-bFGF)采取侧脑室给药途径及生理和病理条件下肌肉给药途径注入豚鼠体内，测量相关组织γ放射计数率及耳蜗放射性自显影，观察^125I-bFGF在耳蜗分布及代谢情况。结果 生理和病理条件下，豚鼠肌肉注射^125I-bFGF后血液和肝脏组织中γ放射性计数率明显高于本底，而脑组织、耳蜗和外淋巴γ放射性计数率与本底比较，变化不明显，耳蜗放射性自显影未见显影颗粒；侧脑室注入^125I-bFGF 30min时，豚鼠血液、肝脏、脑组织、耳蜗及外淋巴γ放射性计数率均已增高，耳蜗放射自显影出现显影颗粒，脑及耳蜗组织γ计数率以2h和4h最高，8h明显下降，耳蜗放射性自显影仍可见显影颗粒，12hγ计数结果仍然高于本底，但耳蜗放射性自显影无明显显影颗粒，24h各脏器γ计数率接近本底；脑组织、耳蜗及血液γ放射性计数率始终保持平行变化。结论 生理情况下，bFGF肌肉注射难以通过血脑屏障和血迷路屏障，而bFGF侧脑室注入后可迅速通过脑脊液与内耳之间的交通径路进入内耳，分布于外淋巴中，且在耳蜗内潴留时间较长；病理情况下如急性缺氧、氨基甙类抗生素耳中毒时，bFGF肌肉注射亦难以通过血脑屏障和血迷路屏障到达内耳；两者对bFGF的通透具有方向性、相似性。     

碱性成纤维细胞生长因子在内耳的生物学作用

碱性成纤维细胞生长因子(bFGF)是多种细胞的促分裂剂，具有广泛的生理功能。bFGF对耳毒性药物或噪声引起的耳蜗毛细胞损伤具有保护作用，还能促进内耳损伤神经元的修复。本就bFGF的生化特性及作用机制，在内耳中的分布，以及在内耳发育、毛细胞再生等方面的作用加以综述。     

成纤维细胞生长因子与鼻息肉上皮细胞增殖

为探讨成纤维细胞生长因子在鼻息肉组织中的表达及其与鼻息肉上皮细胞增殖之间的关系,将２６例鼻息肉标本及１４例下鼻甲标本行ＦＧＦ和增殖细胞抗原的免疫组化染色,光镜观察。结果发现ＰＣＮＡ在鼻息肉组的阳性率（７８．６％）显著高于下鼻甲组（０．０％）,ＦＧＦ在鼻息肉组的上皮及腺体的阳性表达率明显高于下鼻甲组（Ｐ〈０．０１,Ｐ〈０．００１）,且二者的表达具有显著正相关（Ｐ〈０．０１）。我们推测ＦＧＦ对鼻息肉上     

Antioxidant treatment reduces blast-induced cochlear damage and hearing loss

Exposure to blast overpressure has become one of the hazards of both military and civilian life in many parts of the world due to war and terrorist activity. Auditory damage is one of the primary sequela of blast trauma, affecting immediate situational awareness and causing permanent hearing loss. Protecting against blast exposure is limited by the inability to anticipate the timing of these exposures, particularly those caused by terrorists. Therefore a therapeutic regimen is desirable that is able to ameliorate auditory damage when administered after a blast exposure has occurred. The purpose of this study was to determine if administration of a combination of antioxidants 2,4-disulfonyl α-phenyl tertiary butyl nitrone (HPN-07) and N-acetylcysteine (NAC) beginning 1 h after blast exposure could reduce both temporary and permanent hearing loss. To this end, a blast simulator was developed and the operational conditions established for exposing rats to blast overpressures comparable to those encountered in an open-field blast of 14 pounds per square inch (psi). This blast model produced reproducible blast overpressures that resulted in physiological and physical damage to the auditory system that was proportional to the number and amplitude of the blasts. After exposure to 3 consecutive 14 psi blasts 100% of anesthetized rats had permanent hearing loss as determined at 21 days post exposure by auditory brainstem response (ABR) and distortion product otoacoustic emission (DPOAE) testing. Animals treated with HPN-07 and NAC after blast exposure showed a significant reduction in ABR threshold shifts and DPOAE level shifts at 2-16 kHz with significant reduction in inner hair cell (IHC) and outer hair cell (OHC) loss across the 5-36 kHz region of the cochlea compared with control animals. The time course of changes in the auditory system was documented at 3 h, 24 h, 7 day and 21 day after blast exposure. At 3 h after blast exposure the auditory brainstem response (ABR) threshold shifts were elevated by 60 dB in both treated and control groups. A partial recovery of to 35 dB was observed at 24 h in the controls, indicative of a temporary threshold shift (TTS) and there was essentially no further recovery by 21 days representing a permanent threshold shift (PTS) of about 30 dB. Antioxidant treatment increased the amount of both TTS and PTS recovery relative to controls by 10 and 20 dB respectively. Distortion product otoacoustic emission (DPOAE) reached a maximum level shift of 25-30 dB measured in both control and treated groups at 3 h after blast exposure. These levels did not change by day 21 in the control group but in the treatment group the level shifts began to decline at 24 h until by day 21 they were 10-20 dB below that of the controls. Loss of cochlear hair cells measured at 21 day after blast exposure was mostly in the outer hair cells (OHC) and broadly distributed across the basilar membrane, consistent with the distribution of loss of frequency responses as measured by ABR and DPOAE analysis and typical of blast-induced damage. OHC loss progressively increased after blast exposure reaching an average loss of 32% in the control group and 10% in the treated group at 21 days. These findings provide the first evidence that a combination of antioxidants, HPN-07 and NAC, can both enhance TTS recovery and prevent PTS by reducing damage to the mechanical and neural components of the auditory system when administered shortly after blast exposure.     

Effect of minocycline and its nano-formulation on central auditory system in blast-induced hearing loss rat model

Blast injuries are common among the military service members and veterans. One of the devastating effects of blast wave induced TBI is either temporary or permanent hearing loss. Treating hearing loss using minocycline is restricted by optimal drug concentration, route of administration, and its half-life.Therefore, therapeutic approach using novel therapeutic delivery method is in great need. Among the different delivery methods, nanotechnology-based drug delivery is desirable, which can achiev...     

水杨酸钠对噪声性听力损失影响的实验

目的 观察水杨酸钠能否减轻噪声引起的听力损失。方法 将３６只健康且耳廓反射正常的花色豚鼠随机分为水杨酸钠实验组、生理盐水对照组、水杨酸钠对照组和噪声暴露组。噪声暴露采用１０５ｄＢ ＳＰＬ的４ＫＨｚ窄带噪声下暴露２ｈ,连续５ｄ。水杨酸钠给药为每天０．５ｇ／ｋｇ体重连续１０ｄ。由短声诱发听性脑干反应（ａｕｄｉｔｏｒｙ ｂｒａｉｎｓｔｅｍ ｒｅｓｐｏｎｓｅ,ＡＢＲ）,连续测试其阈值;而后取动物双侧耳蜗荧     

褪黑素对噪声性聋的防护作用

目的通过检测耳蜗中活性氧(reactive oxygen species,ROS)的含量研究褪黑素(melatonin,MLT)对噪声性聋的防护作用.方法雄性杂色豚鼠40只,随机分为4组,每组10只.第1组为正常对照组,不接触噪声,仅肌肉注射褪黑素,注射褪黑素的时间及剂量与第2组相同.第2、3、4组每天接触倍频程连续噪声(中心频率为4kHz,强度为100dB SPL)8小时,连续3天.第2组于噪声暴露前24h、即刻及噪声暴露中肌肉注射褪黑素3天.第3组在相同时间肌肉注射与第2组相同剂量的生理盐水.第4组为单纯接触噪声对照组.所有动物均于噪声暴露前及暴露后立即检测听性脑干反应(ABR)阈值,噪声暴露3天测完ABR阈值后,立即断头处死豚鼠,取出双侧耳蜗,并测定其活性氧含量.结果噪声暴露后,第2组的ABR阈移及活性氧含量分别与第3、4组比较,差异均有显著性.结论褪黑素能够减少噪声暴露后耳蜗中增多的活性氧水平,可能对噪声性耳蜗损伤具有一定的防护作用.     

中枢性低频听力减退的听力学分析

目的 加深对双侧中枢性低频听力减退的认识。方法 复习１９８８～２０００年１０１例原因不明的双侧感音神经性低频听力减退患者的听力学检查结果。结果 其共同的特点是：言语听力不成比例地差于纯音听力,诱发性耳声发射正常,不受对侧噪声抑制,引不出镫骨肌声反射,听性脑干反应（ａｕｄｉｔｏｒｙ ｂｒａｉｎｓｔｅｍ ｒｅｓｐｏｎｓｅ,ＡＢＲ）异常,－ＳＰ／ＡＰ振幅比大于０．４４。结论 此类原因不明的低频听力减退患者听力学表现提示：耳蜗外毛细胞功能正常,与声反射、听传出抑制、ＡＢＲ波Ⅲ相关的脑干听觉神经径路为功能障碍的主要部位,可伴有耳蜗或传入神经功能障碍。建议使用“中枢性低频听减退”的名称。     

Central low frequency hearing loss]

Sixteen central hearing loss cases were studied. The typical clinical findings were bilateral low frequency loss, low speech discrimination score, abnormal ABR, predominant-SP, normal EOAE, and normal 40Hz AERP. The possible etiological factor and site of the lesion were discussed.     

Noise-induced hearing loss and tinnitus]

The presence of subjective tinnitus is an important aspect in the evaluation of hearing loss induced by noise. Tinnitus due to this condition is characterised by a frequency of 3,000 Hz or above and is closely related to the frequency range of maximal hearing loss. Tinnitus below 1,000 Hz is not induced by noise, and indicates the presence of a different cause for the hearing loss. This type of tinnitus should not be regarded as an occupational disease: it requires extensive investigation.     

突发性聋预后影响因素

目的对影响突发性聋的预后因素进行分析讨论。方法回顾分析249例突发性聋患者临床资料,包括年龄、初诊时间,初诊时听力损失程度,听力曲线类型,是否伴有眩晕和耳鸣,进行畸变产物耳声发射(distortion product otoacoustic emissions,DPOAE)检查结果。结果初诊时间为发病后1～23天,患侧耳初诊时250 Hz～4000 Hz平均听力损失40dB以下31例(12.45%),41 dB～70 dB 80例(32.13%);71 dB～90 dB 74例(29.72%),91 dB以上64例(25.70%)。听力曲线上升型72例,下降型81例,平坦型96例。伴有眩晕96例,伴耳鸣174例。治疗药物包括血管扩张剂、皮质类固醇激素、神经营养剂、抗病毒及能量合剂,疗程2～4周。81例进行畸变耳声发射检查,45例在不同频率被引出,经治疗最终被引出DPOAE的频率听力恢复达痊愈水平。结论高龄患者和年龄小的患者预后不良;初诊时间越早听力恢复越好;听力曲线上升型预后好;伴有眩晕者预后不好;能引出DPOAE者听力恢复好。     

Treatment of idiopathic sudden sensorineural hearing loss

CONCLUSION: The therapeutic role of corticosteroids and/or corticosteroids with antiviral agents for sudden sensorineural hearing loss (SSNHL) has yet to be fully elucidated; however, in cases where deafness is profound and of recent onset, a therapeutic trial is indicated. OBJECTIVES: To investigate treatment regimens and their efficacies, as well as evaluating the potential prognostic correlates and allowing comparison between local and national standards of care for SSNHL. PATIENTS AND METHODS: A retrospective evidence-based case series of 143 patients seen at the University of Rochester, Department of Otolaryngology between 1999 and 2002 was investigated. Treatment modalities included (1) observation, (2) steroids, and (3) steroids with antivirals. RESULTS: The study demonstrates that steroid treatment, alone or in combination with antivirals, results in a significant improvement rate compared with observation. Results indicate that the more expediently a patient with SSNHL is seen by an otolaryngologist, the better their prognosis.     

单唾液酸四己糖神经节苷脂钠治疗突发性耳聋临床观察

目的 探讨单唾液酸四己糖神经节苷脂钠治疗突发性耳聋的疗效。方法 将突发性耳聋患者80例随机分为治疗组和对照组,治疗组患者给予单唾液酸四己糖神经节苷脂钠静滴,对照组患者给予甲钴胺注射液静推,两组均同时行激素、扩血管药物、高压氧等治疗。10d为一疗程。结果 单唾液酸四己糖神经节苷脂钠组听力提高的总有效率为85%,痊愈率为52.5%;而对照组的总有效率为62.5%,痊愈率为27.5%,两组差异有统计学意义(P<0.05);治疗组耳鸣好转的总有效率为80%,对照组的总有效率为51.7%, 两组差异有统计学意义(P<0.05)。结论 单唾液酸四己糖神经节苷脂钠治疗突发性耳聋疗效相对于其他方法疗效较好。