T 型钙通道拮抗剂对 Cdh23 Erl/Erl 小鼠听觉功能的保护作用

IF 1.9 4区 医学 Q3 INTEGRATIVE & COMPLEMENTARY MEDICINE
Weijun Ma, Heng Li, Juan Hu, Ying Gao, Xiaotong Zhang, Min Xu, Ying Cheng
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引用次数: 0

摘要

背景:在正常生理条件下,钙离子(Ca2+)在调节毛细胞(HC)功能方面具有重要作用,T型钙离子拮抗剂可能对听力损失具有保护作用。然而,目前还没有关于 T 型钙通道拮抗剂在 Cdh23 小鼠模型中的耳保护作用的研究:本研究旨在探讨乙琥胺--一种 T 型钙通道拮抗剂--在 Cadherin 23 (Cdh23) erl/erl 小鼠模型中对老年性听力损失的保护作用,以便在不久的将来为临床上患有老年性听力损失的患者的治疗提供启示和依据:研究小组进行了一项动物研究:动物:12 只雌雄 Cdh23 erl/erl 小鼠:研究小组将小鼠随机分为两组,每组 12 只:(1) 对照组,即生理盐水组,按每公斤体重 10 毫升的剂量接受生理盐水治疗;(2) 干预组,即乙琥胺组,按每公斤体重 10 毫升的剂量接受乙琥胺治疗。两组小鼠均从出生后7天开始,每隔一天腹腔注射一次治疗药物,直至小鼠8周大:对于两组小鼠,研究小组(1) 测量听性脑干反应(ABR);(2) 在小鼠 4、6 和 8 周龄时测量畸变产物耳声发射(DPOAE);(3) 将基底膜与模耳和外侧组织分离,并确定内毛细胞和外毛细胞(IHC 和 OHC)损失的百分比;(4) 使用反转录聚合酶链反应(PCR)检测与细胞凋亡相关的基因 mRNA 的相对水平;以及 (5) 使用免疫荧光(IF)染色检测与细胞凋亡相关的蛋白质的相对水平。结果与生理盐水组相比,乙琥胺组:(1) 8周时点击的ABR阈值、6周和8周时8 KHz的ABR阈值、16 KHz和32 KHz的ABR阈值均显著降低(均P < .01);(2) 4周时15.4 KHz和17.7 KHz的DPOAE振幅显著升高(均P < .01);(3) 4周时16 KHz和32 KHz的DPOAE振幅显著降低(均P < .01)。7 KHz(均 P < .01);6 周时,8.8 KHz(P < .05)、10.1 KHz(P < .01)、11.7 KHz(P < .01)、13.4 KHz(P < .01)、15.4 KHz(P < .01)和 17.7 KHz(P < .01);8 周时为 6.7 KHz(P < .05)、7.7 KHz(P < .05)、10.1 KHz(P < .01)、11.7 KHz(P < .01)、13.4 KHz (P < .01)、15.4 KHz (P < .01) 和 17.7 KHz (P < .01);(3) 耳蜗表面中部和基底转折处的 OHC 损失显著较低(均 P < .05);(4)在 2 个月大时,使用聚合酶链式反应(PCR)发现,与细胞凋亡相关的基因(包括 caspase-3、caspase-9、caspase-12、m-calpain 和 u-calpain)的 mRNA 相对水平明显较低;(5)使用免疫荧光(IF)染色发现,内耳中 caspase-3 和 caspase-9 的蛋白水平较低:结论:T型钙通道拮抗剂对cdh23 erl/erl小鼠的听力功能有保护作用。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Protective Efficacy of T-type, Calcium Channel Antagonist on Auditory Function in Cdh23 Erl/Erl Mice.

Context: In normal physiological conditions, calcium ions (Ca2+) have an important effect in terms of the regulation of hair cell (HC) functions, and T-type calcium antagonists may be protective against hearing loss. However, no studies have occurred related to a T-type calcium-channel antagonist with regard to otoprotection in a Cdh23 mouse model.

Objective: The study intended to examine the protective efficacy of ethosuximide-a T-type calcium-channel antagonist-against age-related hearing loss in a Cadherin 23 (Cdh23) erl/erl mouse model, to potentially offer an insight and foundation for therapy in the near future for patients in clinical practice who suffer from age-related hearing loss.

Design: The research team conducted an animal study.

Animals: The animals were 12 male and 12 female, Cdh23 erl/erl mice.

Intervention: The research team randomly divided the mice into two groups, with 12 mice in each group: (1) the control group, the saline group, which received saline at 10 mL/kg of body weight, and (2) the intervention group, the ethosuximide group, which received ethosuximide at 10 mL/kg of body weight. Both groups received the treatments intraperitoneally every other day, beginning postnatally at 7 days until the mice were 8 weeks old.

Outcome measures: For both groups, the research team: (1) measured auditory brainstem response (ABR); (2) measured distortion product otoacoustic emission (DPOAE) at 4, 6, and 8 weeks of age; (3) separated the basilar membrane from the modiolus and lateral tissues and determined the percentage of inner-and-outer hair-cell (IHC and OHC) loss; (4) investigated relative levels of apoptosis-related gene mRNA using reverse transcription polymerase chain reaction (PCR); and (5) examined relative levels of apoptosis-related protein, using immunofluorescent (IF) staining.

Results: Compared to the saline group, the ethosuximide group: (1) had significantly lower ABR thresholds for click at 8 weeks, for 8 KHz at 6 and 8 weeks, and for 16 KHz and 32 KHz (all P < .01); (2) had significantly higher DPOAE amplitudes at 4 weeks at 15.4 KHz and 17.7 KHz (both P < .01); at 6 weeks at 8.8 KHz (P < .05), 10.1 KHz (P < .01), 11.7 KHz (P < .01), 13.4 KHz (P < .01), 15.4 KHz (P < .01), and 17.7 KHz (P < .01); and at 8 weeks at 6.7 KHz (P < .05), 7.7 KHz (P < .05), 10.1 KHz (P < .01), 11.7 KHz (P < .01), 13.4 KHz (P < .01), 15.4 KHz (P < .01), and 17.7 KHz (P < .01); (3) had significantly lower OHC loss in the middle and basal turns of the cochlea's surface (both P < .05); (4) at the age of 2 months, had significantly lower mRNA relative levels of apoptosis-related genes, including caspase-3, caspase-9, caspase-12, m-calpain and u-calpain, as found using a polymerase chain reaction (PCR); and (5) had weaker protein levels of caspase-3 and caspase-9 in the inner ears, as found using immunofluorescent (IF) staining.

Conclusions: T-type calcium-channel antagonists can exert protective efficacy in terms of the hearing function among cdh23 erl/erl mouse.

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来源期刊
Alternative therapies in health and medicine
Alternative therapies in health and medicine INTEGRATIVE & COMPLEMENTARY MEDICINE-
CiteScore
0.90
自引率
0.00%
发文量
219
期刊介绍: Launched in 1995, Alternative Therapies in Health and Medicine has a mission to promote the art and science of integrative medicine and a responsibility to improve public health. We strive to maintain the highest standards of ethical medical journalism independent of special interests that is timely, accurate, and a pleasure to read. We publish original, peer-reviewed scientific articles that provide health care providers with continuing education to promote health, prevent illness, and treat disease. Alternative Therapies in Health and Medicine was the first journal in this field to be indexed in the National Library of Medicine. In 2006, 2007, and 2008, ATHM had the highest impact factor ranking of any independently published peer-reviewed CAM journal in the United States—meaning that its research articles were cited more frequently than any other journal’s in the field. Alternative Therapies in Health and Medicine does not endorse any particular system or method but promotes the evaluation and appropriate use of all effective therapeutic approaches. Each issue contains a variety of disciplined inquiry methods, from case reports to original scientific research to systematic reviews. The editors encourage the integration of evidence-based emerging therapies with conventional medical practices by licensed health care providers in a way that promotes a comprehensive approach to health care that is focused on wellness, prevention, and healing. Alternative Therapies in Health and Medicine hopes to inform all licensed health care practitioners about developments in fields other than their own and to foster an ongoing debate about the scientific, clinical, historical, legal, political, and cultural issues that affect all of health care.
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