摘要
目的:观察熊果酸对顺铂致毒小鼠耳蜗3-硝基酪氨酸及钙蛋白酶1表达的影响,探究熊果酸对顺铂引起的耳毒性的防护作用及其机制。方法:选用5周龄健康BALB/c小鼠,随机分成对照组、熊果酸组(80 mg/kg)、顺铂组(4.5 mg/kg)及顺铂(4.5mg/kg)联合熊果酸(80 mg/kg)组。各组动物均连续腹腔注射给药5天,每天1次。应用Western blot技术及显微图像分析观察小鼠耳蜗中3-硝基酪氨酸和钙蛋白酶1的表达,并结合听脑干反应(ABR)检测并观察用药前后小鼠听阈的改变。此外,采用Fluo-3/AM染色法检测小鼠耳蜗内Ca^(2+)的浓度改变。结果:熊果酸(80 mg/kg)联合顺铂小鼠听脑干反应阈移和耳蜗内Ca^(2+)浓度的升高以及耳蜗3-硝基酪氨酸和钙蛋白酶1的表达均明显低于顺铂组。结论:熊果酸(80 mg/kg)可通过显著抑制顺铂所致3-硝基酪氨酸、钙蛋白酶1的高表达以及细胞内Ca^(2+)浓度的升高,从而有效拮抗顺铂的耳毒性,改善听功能。
Objective： To investigate the effect of ursolic acid（ UA） on cisplatin（ CDDP）-induced expression of 3-Nitro-Tyrosine（ 3-NT） and calpain1 in mouse cochlea,and to explore the protective role and mechanism of UA on CDDP-induced ototoxicity.Methods： healthy BALB/c mice were randomly divided into control group,UA group（ 80 mg/kg）,CDDP group and CDDP plus UA（ 80 mg/kg） group.Mice from each group were continuously given drugs by introperitoneal injection once daily for 5 days.Expressions of 3-NT and calpain in mouse cochlea were detected by microscope image analysis and western blot technique.Auditory threshold was tested by auditory brainstem response（ ABR）measurement.In addition,Fluo-3/AM was used to measure concentrations of calcium in mouse cochlea.Results： Expressions of 3-NT and calpain1; change of concentrations of calcium and ABR threshold shift in CDDP plus UA（ 80 mg/kg） group were significantly declined as compared with CDDP group（ P 〈 0.05,P 〈 0.01）.Conclusions： UA（ 80 mg/kg） could effectively attenuate CDDP ototoxicity by inhibiting high-expression of 3-NT,calpain1 and increased concentrations of calcium so as to improve auditory function.
出处
《中药药理与临床》
CSCD
北大核心
2017年第1期49-52,共4页
Pharmacology and Clinics of Chinese Materia Medica
基金
2014年辽宁省大学生创新训练项目(乙类:201410160030)
