熊果酸对顺铂致毒小鼠耳蜗瞬时感受器电位香草酸受体1表达的影响

The Effects of Ursolic Acid on Cisplatin-Induced Expression of Transient Receptor Potential Vanilloid 1 in Mouse Cochlea

邸阳;于利;田原;林宇涵;王爱梅;

1:辽宁医学院生理学教研室

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摘要

目的研究熊果酸(ursolic acid,UA)对顺铂(cisplatin,CDDP)致毒小鼠耳蜗瞬时感受器电位香草酸受体1(transient receptor potential vanilloid 1,TRPV1)表达的影响。方法 60只健康BALB/c小鼠随机分成对照组(腹腔注射等量生理盐水)、UA组(腹腔注射熊果酸80mg/kg)、CDDP组(腹腔注射CDDP 4.5mg/kg)和CDDP+UA组(一侧腹腔注CDDP 4.5mg/kg,同时对侧腹腔注射熊果酸80mg/kg),每组15只。各组动物均连续腹腔注射给药5天,每天1次,给药前及停药后24h行ABR检测,然后应用免疫组织化学染色、显微图像分析及蛋白质印迹技术观察小鼠耳蜗中TRPV1的表达。结果 CDDP组小鼠耳蜗TRPV1表达和ABR阈移均较对照组明显增加(P<0.05),UA+CDDP组小鼠ABR阈移及TRPV1表达较CDDP组明显降低(P<0.05),且TRPV1表达变化与ABR阈移改变高度相关(|r|>0.7,P<0.05)。结论 UA可抑制CDDP所致TRPV1的高表达,有效降低CDDP的耳毒性,改善听功能。

关键词

熊果酸;顺铂;耳蜗;瞬时感受器电位香草酸受体1

基金项目(Foundation):

辽宁省科学技术计划项目(2011225015)

作者

邸阳;于利;田原;林宇涵;王爱梅;

参考文献

1 Zheng J,Dai C,Steyger PS,et al.Vanilloid receptors in hearing:altered cochlear sensitivity by vanilloids and expression of TRPV1in the organ of corti[J].J Neurophysiol,2003,90:444.

2 才岩,王爱梅,于利,等.瞬时受体电位通道蛋白A1和V1在正常小鼠耳蜗中的定位表达[J].中国现代医学杂志,2012,22:1.

3 Mukherjea D,Jajoo S,Whitworth C,et al.Short interfering RNA against transient receptor potential vanilloid 1attenuates cisplatin-induced hearing loss in the rat[J].J Neurosci,2008,28:13056.

4 Tsai SJ,Yin MC.Antioxidative and anti-inflammatory protection of oleanolic acid and ursolic acid in PC12cells[J].J Food Sci,2008,73:174.

5 Checker R,Sandur SK,Sharma D,et al.Potent anti-inflammatory activity of ursolic acid,a triterpenoid antioxidant,is mediated through suppression of NF-κB,AP-1and NFAT[J].PLoS One,2012,7:e31 318.

6 Chang L,Wang AM.Calpain mediated cisplatin-induced ototoxicity in mice[J].Neural Regen Res,2013,8:1 995.

7 Wang AM,Hou N,Bao DY,et al.Mechanism of alpha-lipoic acid in attenuating kanamycin-induced ototoxicity[J].Neural Regen Res,2012,7:2793.

8 Lee JE,Nakagawa T,Kim TS,et al.Role of reactive radicals in degeneration of the auditory system of mice following cisplatin treatment[J].Acta Otolaryngol,2004,124:1131.

9 Ho KW,Ward NJ,Calkins DJ.TRPV1:a stress response protein in the central nervous system[J].Am J Neurodegener Dis,2012,1:1.

10 Mukherjea D,Jajoo S,Sheehan K,et al.NOX3NADPH oxidase couples transient receptor potential vanilloid 1to signal transducer and activator of transcription 1-mediated inflammation and hearing loss[J].Antioxid Redox Signal,2011,14:999.

11 Ishibashi T,Takumida M,Akagi N,et al.Changes in transient receptor potential vanilloid(TRPV)1,2,3and 4expression in mouse inner ear following gentamicin challenge[J].Acta Otolaryngol,2009,129:116.

12 Lee JH,Park C,Kim SJ,et al.Different uptake of gentamicin through TRPV1and TRPV4channels determines cochlear hair cell vulnerability[J].Exp Mol Med,2013,45:e12.

13 Hong SY,Jeong WS,Jun M.Protective effects of the key compounds isolated from corni fructus againstβ-amyloidinduced neurotoxicity in PC12 Cells[J].Molecules,2012,17:10831.

14 Yu HH,Hur JM,Seo SJ,et al.Protective effect of ursolic acid from Cornus officinalis on the hydrogen peroxide-induced damage of HEI-OC1auditory cells[J].Am J Chin Med,2009,37:735.

15 Zhang Y,Sreekrishna K,Lin Y,et al.Modulation of transient receptor potential(TRP)channels by Chinese herbal extracts[J].Phytother Res,2011,25:1666.

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熊果酸顺铂耳蜗瞬时感受器电位香草酸受体1

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邸阳于利田原林宇涵王爱梅