Basic fibroblast growth factor protects auditory neurons and hair cells from noise exposure and glutamate neurotoxicity

［1］Zheng, J. L., Stewart, R.R., Gao, W.Q. neurotrophin -4/5 enhances survival of cultured spiral ganglion neurons and protects them from cisplatin neurotoxicity. J. Neurosci, 1995, 15:5079 -5087. ［2］Zheng, J.L., Helbig, C., Gao, W.Q., induction of cell proliferation by fibroblast and insulin- like growth factors in pure rat inner ear epithelia cell cultures. J. Neurosci, 1997, 17:216-226. ［3］Shoji, F., Miller, A. L., Nitchell, A., Yamasoba, T., Altschuler,R.A., Miller, J.M. Differential protective effects of neurotrophins in the attenuation of noise- induced hair cell loss. Hear. Res, 2000,146: 134- 142. ［4］Baird, A. Fibroblast growth factors: activities and significance of nonneurotrophin neurotrophinc growth factors. Curr Opin Neurobiol..Curr Opin Neurobiol, 1994, 4:78 - 86. ［5］Mason, I. J., Fuller, P.F., Smith, R., Dickson, C. FGF-7(keratinocyte growth factor) expression during mouse development suggests roles in myogenesis, forebrain regionalisation and epithelial - mesenchymal in teractions. Mech. Dev, 1994, 45:15 - 30. ［6］Johnson, D. E., Williams4 L. T. Structural and functional diversity in FGF receptor multigene family. Adv. Cancer Res, 1993, 60:1 -41. ［7］Pirvola, U., Cao, Y., Oellig, C., Suoqiang, Z., Pettersson, R.F.,Ylikoski, J. The site of action of neuronal acidic fibroblast growth factor is the organ of Corti of rat cochlea. Proc. Natl. Acad. USA, 1995,92:9269 - 273. ［8］Lefebvre, P. P., Van De Water, T. R., Weber, T., Rogister, B., Moonen, G. Growth factor interations in cultures of dissociated adult acoustic ganglia: neuronotrophic effects. Brain Res, 1991, 567:306 - 312. ［9］Hossain, W.A., Rutledge, A., Hossain, A., Baler, C.N., Morest,D. K. Basic fibroblast growth factor(FGF-2) affects neuronal migration and differentiation in thechicken acoustic ganglion. In Assoc. Res,Otolaetngol. Abstr., 18m Midwinter Meeting, 1995. 109. ［10］Low, W., Dazert, S., Baird, A., Ryan, A. F. Basic fibroblast growth factor(FGF-2) protects rat cochlear hair cells in organotypical culture from aminoglycoside injury. J. Cell. Physiol, 1996, 167:443 -450. ［11］Dalian Ding., Xiangyang Zheng., Jian Wang., Wei Sun, Hong Sun.,Richard J. Salvi. Mechanisms of carboplatin ototoxicity suggested by cytochemical analysis. Journal of Audiology and Speech Pathology,1999, 7:200 - 202. ［12］Gleich O., Wilson S. The diameters of guinea pig auditory nerve fibers: distribution and correlation with spontaneous rate. Hear Res,1993, 71:69 - 79. ［13］Dazert, S., Baird, A., Ryan, A.F. Receptor-targeted delivery of an intracellular toxin to outer hair cells by fibroblast growth factor.Hear. Res, 1998, 115:143 - 148. ［14］Luo, L., Koutnouyan, H., Baird, A., Ryan, A.F. Acidic and basic FGF mRNA expression in the adult and developing rat cochlea.Hear. Res, 1993, 69:182 - 193. ［15］Lefebvre, P.P., Van de Water, T. R., Staecker, H., Weber, T.Galinovi‘ c, Schwartz, V., Moonen, G. Nerve growth factor stimulates neurite regeneration but not survival of adult auditory neurons in vitro.Acta Otolaryngol (Stockh), 1992, 112:288 - 293. ［16］Choi, D.W., Excitotoxic cell death. J. Neurobiol, 1992, 23:1261 - 1276. ［17］Pujol, R., Puel, J, L., Gervais d‘ Aldin, C., Eybalin, M., Pathophysiology of the glutamatergic synapses in the cochlea. Acta otolaryngol. (Stockholm), 1993, Ⅱ 3: 330-334. ［18］Puel, J.L., D‘Aldin, C., Ruel, J., ladrech, S., Pujol, R., Perspectives in inner ear pharmacoclogy and clinical applications. In:Prasher, D., canlon, B. (Eds.), Cochlear Pharmacoclogy and Noise trauma. NRN Publications, London, 1999. pp 1 - 11. ［19］Scheibe, F., Haupt, H., Ludwig, C., Intensity - dependent changes in oxygenation of cochlear perilymph during acoustic exposure. Hear.Res, 1992, 63:19 - 25. ［20］Ohlemiller, K.K., Dugan, L.L., In vivo measurement of cochlear reactive oxygen species (ROS) in mice. Effects of noise exposure and cochlear ischemia. Assoc. Res. Otolartngol. Abstr. 1998.21, 130. ［21］Yamane, H., Nakai, Y., Takayama, M., Iguchi, H., Nakagawa,T., Kojima, A., Appearance of free radicals in the guinea pig inner ear after noise-induced acoustic trauma. Eur. Arch. Otorhinolaryngol,1995, 252:504 - 508. ［22］Hu, B.H., Zheng, X.Y., McFadden, S.L., Kopke, R.D., Henderson, D. , R - phenylisopropyladenosine attenuates noise - induced hearing loss in the chinchilla. Hear. Res, 1997, 113:198 -206. ［23］Yamasoba, T., Schacht, J., Shoji, F., Miller, J.M., Attenuation of cochlear damage from noise trauma by an iron chelator, a free radical scavenger and glial cell line - derived neurotrophic factor in vivo. Brain Res. 1999. 815, 317 -325. ［24］Kristian, T., Sjesjo, B.K., Calcium in ischemic cell death. Stroke,1998, 29:705 - 718. ［25］Mattson, M.P., Furukawa, K., Programmed cell life: anti - apoptotic signaling and therapeutic strangies for neurodegenerative disorders.Restor. Neurol. Neurosci, 1996, 9:191 - 205. ［26］Lee, K.H., Cotanche, D.A., Potential role of bFGF and retinoic acid in the regeneration of chicken cochlear hair cells. Hear Res,1996, 94:1 - 13. ［27］Adamis, A.P., Meklir, B., Joyce, N. C. in situ injury-induced release of basic -fibroblast growth factor from corneal epithelial cells.Am. J. Pathol, 1991, 139:961 -967. ［28］McNeil, P. L., Muthukrishnan, L., Warder, E., D‘Amore, P. A.Growth factors are released by mechanically wounded endothelial cells.J. Cell Biol, 1989, 109:811 -822. ［29］Saito, H., Kasyyama, S., Kouhara, H., Matsumoto, K., Sato, B.,Up- regulation of fibroblast growth factor(FGF) receptor mRNA levels by basic FGF or testosterone in androgen-sensitivy mouse mammary tumor cells. Biochem. Biophys. Res. Commun, 1991, 174:136 - 141. ［30］Privola, U., Spencer-Dene, B., Xing- Qun, L., Kettunen, P.,Thesleff, I., Fritzsch, B., Dickson, C., Ylikoski, J. FGF/FGFR-2(Ⅲb) signaling is essential for inner ear morphogenesis. J. Neurosci,2000, 16; 6125 - 6134. ［31］Ornitz, D.M.,Xu, J., Colvin, J.S., McEwen, D.G., MacArthur,C. A., Coulier, F., Gao, G., Goldfarb, M. Receptor specificity of the fibroblast growth factor family. J. Biol. Chem, 1996, 271: 15292 -15297.     

氢化可的松-羟丙基-β-环糊精包合物制备工艺的研究

目的:制备氢化可的松-羟丙基-β-环糊精包合物(HC-HP-β-CD),并初步考察其溶解性。方法:采用超声法制备HC-HP-β-CD,并利用正交实验设计筛选出包合物制备的最佳工艺,测定了包合物及HC的溶解度,比较了二者的紫外吸收光谱变化、X-射线衍射图谱、差示扫描量热图谱以及其在水中的溶解性。结果:通过比较包合物中药物浓度大小,确定包合最佳条件为HP-β-CD与HC比率为2:1,包合时药物浓度为3mg·mL~(-1),包合时间为20min。包合后HC的晶体衍射峰消失,差示扫描量热法测定结果显示形成一种新物相,使氢化可的松的溶解度增大了267倍,且常温下稳定性好。结论:HC与HP-β-CD形成新物相,明显提高了HC的水溶性,制成注射剂可避免通常普通制剂中的溶媒乙醇对机体的不良刺激。     

超声治疗外阴白色病变30例临床分析

目的 :探讨超声治疗外阴白色病变的临床疗效。方法 :收治外阴白色病变 6 0例 ,随机分为 :超声治疗组 30例 ,微波治疗对照组 30例。观察其临床症状、体征和组织学变化。结果 :超声治疗组 30例患者的外阴瘙痒症状基本消失 ,患处上皮不同程度地恢复正常 ,显效率达 90 %。不同的病理类型间疗效的比较 ,差异无显著性 (P >0 .0 5 )。结论 :用超声治疗外阴白色病变效果明显     

Graves病大鼠甲状腺细胞中MAPK的表达及益气养阴中药对其影响

[目的]研究病毒性弥漫性甲状腺肿(Graves病)大鼠(GD大鼠)甲状腺细胞中丝裂原激活的蛋白激酶(MAPK)的表达及益气养阴中药对其影响。[方法]益气养阴中药灌胃GD大鼠，免疫组化法观察其甲状腺细胞中MAPK的表达。[结果]中药组MAPK表达明显减弱。[结论]益气养阴中药具有对抗细胞间信息传导的治疗作用。     

人肝癌原发性耐药细胞亚系的建立及耐药机制的初步探讨

目的从人肝癌细胞系HeFG2中筛选出原发性耐药株,建立相应的细胞亚系并探讨其耐药机制.方法采用阿霉素(adriamycin,ADM)大剂量冲击法筛选原发性耐药细胞株,倒置显微镜下观察其形态学变化,细胞计数法绘制生长曲线,MTT法检测药物敏感性,流式细胞术分析细胞周期和检测耐药蛋白的表达.结果随冲击次数的增加,筛选出细胞的耐药指数(resistance index, RI)逐渐升高,筛选3次后对ADM的RI可达30.5;其形态学特点、生长特性及细胞周期分布与亲本细胞有明显差异,同时发现耐药蛋白P-gp、MRPt LRP表达增强.结论肝癌细胞系HepG2是个非均质的群体,其中存在着原发性耐药细胞株.     

胃粘膜瓣成型预防食管胃吻合术后反流的观察

目的:介绍胃粘膜瓣成型预防食管胃吻合术后反流的临床应用.方法:食管、贲门癌50例,行部分食管部分胃切除,用吻合器作食管胃吻合后行胃粘膜瓣成型.结果:成型组术后无反流症状,上消化道造影及放射性核素显像表明该手术方法抗反流作用明显.食管镜检查示胃粘膜瓣成型组吻合口粘膜充血、水肿、糜烂、溃疡较常规手术组明显减轻.结论:胃粘膜瓣成型术可有效预防食管胃吻合术后胃食管反流.     

BR提取物对小鼠S_(180)肉瘤抑制作用的研究

目的探讨BR提取物对小鼠S180肉瘤生长的抑制作用。方法将昆明种小鼠随机分为正常对照组、肿瘤对照组、试验Ⅰ组、试验Ⅱ组、试验Ⅲ组,除正常对照组外,其余4组均接种S180肉瘤肿瘤细胞悬液,正常对照组和肿瘤对照组均饮用自来水,试验Ⅰ组、试验Ⅱ组、试验Ⅲ组分别饲以4%,2%,1%的BR提取物。结果试验Ⅰ组肿瘤生长抑制率(71.81%)、生命延长率(43.24%)、小鼠体质量下降幅度明显高于试验Ⅱ组和试验Ⅲ组。结论BR提取物对小鼠S180肉瘤的生长有明显抑制作用。     

支气管哮喘患儿体液免疫功能及血浆白细胞介素-6和γ-干扰素的变化

目的 :探讨支气管哮喘患儿体液免疫、补体变化及血浆白细胞介素 - 6和 γ-干扰素与哮喘的病情程度之间的关系。方法 :对 37例支气管哮喘患儿进行外周血体液免疫及补体含量检测 ,同时测定急性发作期治疗前后血浆 IL- 6与 IFN- γ水平 ,与 34例健康对照组比较。结果 :支气管哮喘患儿外周血 Ig G、C3、C4明显降低 ,Ig E明显升高 ,Ig M、Ig A无明显变化。哮喘急性发作期血浆 IL- 6水平高于对照组 ,临床缓解期仍高于对照组。哮喘急性发作期血浆 IFN- γ水平低于对照组和临床缓解期 ,差异具有显著性 (P<0 .0 1 )。结论 :支气管哮喘存在着体液免疫功能紊乱 ,在哮喘发作期和缓解期均有血浆 IL- 6与 IFN- γ平衡失调 ,Th1 / Th2失衡在支气管哮喘发病机理中占重要地位。     

泪点栓塞治疗眼干燥症

目的　探讨泪点栓塞治疗眼干燥症的手术方法 ,评价临床治疗效果。方法　临床确诊并经其他方法治疗无效眼干燥症患者 ,先采用临时性可溶性泪点栓治疗 ,对其中有效者行永久性泪点栓 ,栓塞泪点及泪小管。结果　栓塞后所有病例症状均有所改善 ,其中完全消失 2 5例 ,减轻 7例。角膜荧光素着色明显减少 ,泪液量明显增加 ,泪液分泌试验由治疗前的平均(2 67± 1 3 2 )mm到治疗后的 (10 13± 2 16)mm。泪膜破裂时间明显延长 ,术前平均 (3 42± 0 93 )秒 ,术后平均 (8 3 4± 3 5 8)秒。均无明显并发症。结论　采用泪点栓塞治疗眼干燥症可以有效地减少泪液排出 ,延长泪膜破裂时间 ,重建泪液平衡 ,动态地改变眼表面泪液动力学。具有操作简单、疗效确切、并发症少及有可逆性等优点     

缺氧缺血性脑损伤新生猪海马皮层细胞色素C氧化酶活性变化

目的　研究缺氧缺血性脑损伤 (HIBD)新生猪海马皮层细胞色素C氧化酶 (COX)活性变化。方法　50只 3d新生猪随机分为实验组和对照组 (假手术组 )。实验组制成HIBD模型后置空气中 ,根据在空气中放置时间分 4组 (0h组 ,2 4h组 ,48h组 ,72h组 ) ,每组 10只。每只新生猪分离左侧海马皮层线粒体 ,用分光光度计测定其COX活性 ;采用SDS -PAGE分析线粒体蛋白改变。结果　 1.0h组COX活性与对照组无显著性差异(P >0 .0 5) ,再灌注时开始下降 ,2 4h组活性最低 (P <0 .0 5) ,然后逐渐回升 ,但 72h组仍未恢复至对照水平(P <0 .0 5)。 2 .SDS -PAGE示 2 4h组、48h组和 72h组线粒体蛋白成分和结构与对照组比较有明显差异。结论　HIBD后再灌注线粒体COX活性下降 ,线粒体蛋白成分和结构发生明显变化 ,此为线粒体能量代谢障碍的直接原因 ,也是HIBD中线粒体对神经元凋亡起关键作用的理论基础。