中国病理生理杂志2024,Vol.40Issue(2):291-300,10.DOI:10.3969/j.issn.1000-4718.2024.02.012
甘草酸抑制C57BL/6J小鼠耳蜗炎症减轻顺铂诱导的耳毒性
Glycyrrhizic acid alleviates cisplatin-induced ototoxicity by inhibiting in-flammation of cochlear in C57BL/6J mice
摘要
Abstract
AIM:To study whether glycyrrhizic acid(GL)can resist the ototoxicity of cisplatin(CDDP)in mice and its molecular mechanism.METHODS:Male C57BL/6J mice were divided into 5 groups:control group,DMSO(5%)group,CDDP(4 mg/kg)group,CDDP+low-dose(50 mg/kg)GL group,and CDDP+high-dose(100 mg/kg)GL group(n=14).Auditory brainstem response(ABR)was used to detect hearing changes of mice.HE staining was used to observe the morphological change of cochlear stria vascular in mice.Evans blue(EB)staining was used to observe the per-meability change of the blood-labyrinth barrier(BLB).Immunohistochemical technique was used to detect the expression and distribution of adhesion protein VE-cadherin and tight junction protein ZO-1 on the cochlear stria.ELISA assay and immunofluorescence technology were employed to detect the expression of tumor necrosis factor-α(TNF-α)and interleu-kin-1β(1L-1β).RESULTS:In CDDP group,ABR waveforms of all frequencies were disturbed,the hearing threshold was significantly increased,and I wave latency was prolonged(P<0.05).In CDDP+GL group,ABR waveforms of various frequencies were well differentiated,the hearing threshold was significantly decreased,and the latency of I-wave was shortened(P<0.01).The disordered morphology and more vacuoles in the stria vascularis were observed by HE staining in CDDP group.The GL alleviated CDDP-induced damage in the stria vascularis.In EB staining,CDDP caused an increase in per-meability of BLB(P<0.01),which was improved by GL treatment(P<0.01).Immunohistochemical results showed that the expression of VE-cadherin and ZO-1 in CDDP group were decreased(P<0.01),which was restored in CDDP+GL group(P<0.01).The ELISA and immunofluorescence results showed that the expression of IL-1β and TNF-α was in-creased after CDDP treatment(P<0.01),which was restored in CDDP+GL group(P<0.01).CONCLUSION:The GL alleviates CDDP-induced hearing loss in mice by inhibiting CDDP-induced inflammation and reducing the permeability of BLB.关键词
顺铂/耳毒性/甘草酸/耳蜗炎症/血迷路屏障Key words
cisplatin/ototoxicity/glycyrrhizic acid/cochlear inflammation/blood-labyrinth barrier分类
医药卫生引用本文复制引用
张钰倩,曾宪思,姜文君,吕昊,盛子轩,黄子芸,柴文敏,肖婧,李阳,李丽..甘草酸抑制C57BL/6J小鼠耳蜗炎症减轻顺铂诱导的耳毒性[J].中国病理生理杂志,2024,40(2):291-300,10.基金项目
国家级大学生创新训练项目(No.202310354023) (No.202310354023)
嘉兴大学大学生研究训练计划(No.8517221143) (No.8517221143)