氨基糖苷类抗生素耳毒性的保护和修饰
伍越1郑静1郑斌娇1方芳1梁玲芝1吕建新1管敏鑫1,2
1 温州医学院attardi线粒体生物医学研究院(温州325035)
2 浙江大学生命科学学院 (杭州310058)
[摘要]目的 氨基糖苷类抗生素的分离和鉴定距今已70多年,对治疗严重革兰阴性菌感染,如肠球菌和结核杆菌感染有着强大的功效。然而,随着氨基糖苷类抗生素用药疗程的延长或(和)剂量的增加往往导致肾毒性和耳毒性,阻碍了其在临床上的广泛应用。由于非耳毒性抗生素也具有较广的抗菌谱,用于许多系统感染性疾病的治疗,使得曾经作为优先选择使用的氨基糖苷类抗生素逐渐被取代。然而现在,氨基糖苷类抗生素处于一个潜伏的复兴时期,正逐渐用于治疗对大多数一线抗生素耐受生物所引起的严重性感染,如多重耐药结核、复杂性院内获得性急性尿路感染等。氨基糖苷类抗生素使用的增加,再次向科学家和医生提出了挑战,即肾毒性和耳毒性的问题,尤其该类抗生素导致的耳聋对于具有遗传易感性的患者往往是极重度且不可逆转的。基于这个原因,在过去二十年里,科学家提出了很多种分子治疗策略与氨基糖苷类抗生素导致的耳毒性副作用相抗衡。本文主要概述了:①氨基糖苷类药物杀菌的分子机制,②氨基糖苷类抗生素如何导致具有遗传易感倾向的患者发生耳毒性,③到目前为止,在临床实验和/或临床上已被证明的能阻止和调节氨基糖苷类耳毒性的药物和化合物,④减少氨基糖苷类抗生素剂量来减少耳毒性的发生率。
氨基糖苷类抗生素;耳毒性;非综合征型耳聋;链霉素;巴龙霉素;庆大霉素;新霉素;阿司匹林R978.12A1672-2922(2012)02-0260-010
DOI:10.3969/j. issn. 1672-2922.2012.02.029
基金项目:国家自然科学基金项目(81070794);国家“973”重大
基础研究前期研究专项(2004CCA02200);浙江省重大科技专项社会
发展项目(2007C13021)。
万方数据
垂伸、阅读、转肽、移位、和终』
制或破坏,最终起到杀菌作万方数据
陡用的,因为它们
:蜗和前庭内迅速
tan的特点是在内万方数据
殳病率分析表
LtDNA)单倍型
30次以上的独
弪在意大利的
意大利血统的万方数据
;由引起线粒体
类抗生素)产生
?种向圆窗输送万方数据
醌和苯酚,在体内
An代谢活化产生
:大霉素催化的超万方数据
七应激和由
FNK融合到
FNK就很容
起的损伤的万方数据
殳是一个饱和
SDD处理时,
理时,内耳细
lⅡ了细胞内氨万方数据
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万方数据
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收稿日期:2012-3-30
万方数据
氨基糖苷类抗生素耳毒性的保护和修饰
作者:伍越, 郑静, 郑斌娇, 方芳, 梁玲芝, 吕建新, 管敏鑫
作者单位:伍越,郑静,郑斌娇,方芳,梁玲芝,吕建新(温州医学院attardi线粒体生物医学研究院 温州325035), 管敏鑫(温州医学院attardi线粒体生物医学研究院 温州325035;浙江大学生命科
学学院 杭州310058)
刊名:
中华耳科学杂志
英文刊名:Chinese Journal of Otology
年,卷(期):2012,10(2)
参考文献(40条)
1.丁大连;金晓杰;赵纪余卡那霉素在耳蜗毛细胞中的积聚部位 1997
2.Smith DG;Waksman SA Tuberculostatic and tuberculocidal properties of streptomycin 1947
3.Schaeffer AJ NIDDK-sponsored chronic prostatitis collaborative research network(CPCRN) 5-year data and treatment guidelines for bacterial prostatitis 2004(Suppl.1)
4.Santucci RA;Krieger JN review of efficacy,single daily dosing and ' switch 'therapy 2000
5.Guan MX;Fischel-Ghodsian N;Attardi G A biochemical basis for the inherited susceptibility to aminoglycoside oto-toxicity 2000
6.Gianpaolo Perletti;Anne Vral;Maria Cristina Patrosso Prevention and modulation of aminoglycoside ototoxicity 2008
7.Takeuchi S;Ando M;Kakigi A Mechanism generating endocochlear potential:role played by intermediate cells in stria vascularis 2000
8.Jiang H;Sha SH;Schacht J Rac/Rho pathway regulates actin depolymerization induced by aminoglycoside antibiotics 2006
9.Li Z;Li R;Chen J Mutational analysis of the mitochondrial 12S rRNA gene in Chinese pediatric subjects with aminoglycoside-induced and non-syndromic hearing loss 2005
10.Prezant TR;Agapian JV;Bohlman MC Mitochondrial ribosomal RNA mutation associated with both antibiotic-induced and non-syndromic deafness 1993(03)
11.管敏鑫;赵立东与氨基糖苷类抗生素耳毒性相关的线粒体12SrRNA突变的流行病学特征 2006(02)
12.Guan MX;Yah Q;Li X Mutation in TRMU related to transfer RNA modification modulates the phenotypic expression of the deafness-associated mitoehondrial 12S ribosomal RNA mutations 2006
13.龚莎莎;郑静;张婷氨基糖苷类抗生素耳毒性相关的线粒体DNA突变 2011(04)
14.Guan MX Mitochondrial 12S rRNA mutations associated with aminoglycosideototoxicity 2011
15.杨爱芬;郑静;吕建新修饰因子对线粒体DNA突变致聋的影响 2011(02)
16.龚莎莎;郑静;张婷氨基糖苷类抗生素耳毒性相关的线粒体DNA突变 2011(04)
17.张婷;曾爱平;郑静与耳聋相关的线粒体12SrRNA突变 2012(04)
18.Jacobs HT;Hutchin TP;K(a)ppi T Mitochondrial DNA mutations in patients with postlingual,non-syndromic hearing impairment 2005
19.Zhao H;Young WY;Yan Q Functional characterization of the mitochondrial 12S rRNA C1494T mutation associated with aminoglycoside-induced and nonsyndromic hearing loss 2005
20.Guan MX;Fischel-Ghodsian N;Attardi G Nuclear background determines biochemical Phenotype in the
deafness-associated mitoehondrial 12S rRNA mutation 2001
21.Qian Y;Guan MX Interaction of aminoglycosides with human mitochondrial 12S rRNA Carrying the deafness-associated mutation 2009
22.Ohtani I;Ohtsuki K;Aikawa T Mechanism of proteetive effect of fosfomycin against amino-glycoside ototoxicity 1984
23.Garetz SL;Altschuler RA;Schacht J Attenuation of gentamicin ototoxicity by glutathione in the guinea pig in vivo 1994
24.Momiyama J;Hashimoto T;Matsubara A Leupeptin,a calpain inhibitor,protects inner ear hair cells from aminoglycoside ototoxicity 2006
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26.Jiang H;Sha SH;Schacht J NF-kappaB pathway protects cochlear.hair cells from aminoglycoside-induced ototoxicity 2005
27.Sinswat P;Wu WJ;Sha SH Protection from ototoxicity of intraperitoneal gentamicin in guinea pig 2000
28.Jiang H;Sha SH;Schacht J NF-kappaB pathway protects cochlear hair cells from aminoglycoside-induced ototoxicity 2005
29.Chen Y;Huang WG;Zha DJ Aspirin attenuates gentamicin orotoxicity:from the laboratory to the
clinic 2007
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32.Long M;Smouha EE;Qiu D Flavonoid of Drynaria fortunei protects against gentamicin ototoxicity 2004
33.Low W;Dazert S;Baird A Basic fibroblast growth factor(FGF-2) protects rat cochlear hair cells in organo-typical culture from aminoglycoside injury 1996
34.Staecker H;Dazert S;Malgrange B Transforming growth factor alpha treatment alters intracellular calcium levels in hair cells and protects them from ototoxic damage in vitro 1997
35.McFadden SL;Ding D;Salvemini D M40403,a superoxide dismutase mimetic,protects cochlear hair cells from gentanicin,but not cisplatin toxicity 2003
36.Yarin YM;Amarjargal N;Fuchs J Argon protects hypoxia-,cisplatin-and gentamicin-exposed hair cells in the newborn rat's organ of Corti 2005
37.Kashio A;Sakamoto T;Suzukawa K A protein derived from the fusion of TAT peptide and FNK,a Bcl-
x(L) derivative,prevents cochlear hair cell death from aminoglycoside ototoxicity in vivo 2007
38.Oliveira JA;Canedo DM;Rossato M Sclf-protection against aminoglycoside ototoxicity in guinea pigs 2004
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a spin trap:I.Acute effects 1998
40.Bailey RR;Begg E J;Smith AH Prospective,randomized,controlled study comparing two dosing regimens of gentamicin/oral ciprofloxacin switch therapy for acute pyelonephritis 1996
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