Shi Lijuan, An Yuxiang, Wang Aimei, Gao Qinghua, Yang Yu
Department of Physiology, College of Basic Medical Sciences, China Medical University, Shenyang, China.
Department of Physiology, College of Basic Medical Sciences, China Medical University, Shenyang, China.
Am J Otolaryngol. 2014 Mar-Apr;35(2):171-9. doi: 10.1016/j.amjoto.2013.08.022. Epub 2013 Oct 9.
The clinical use of aminoglycoside antibiotics is limited in most countries because of auditory toxicity side effects. However, their use is common in developing countries because they are inexpensive and convenient. Salvia miltiorrhiza extracts are used clinically in China for their antioxidant properties. We investigated the effect of a clinically approved injectable S. miltiorrhiza solution on inducible nitric oxide synthase (iNOS) generation induced by the aminoglycoside antibiotic gentamicin and an ototoxicity protective mechanism.
Sixty adult guinea pigs were used in this study and divided into four groups. Auditory brainstem response (ABR) testing was performed before and after treatments and animals were sacrificed for morphological and immunostaining assays after determining threshold shifts in ABR. The cochleae were examined by transmission electron microscopy (TEM) and scanning electron microscopy (SEM) to observe ultrastructural changes. In addition, hair cell loss, iNOS and caspase-3 expression, and apoptosis were measured.
The result showed that hearing loss, iNOS overexpression accompanied with disorganization in the cochlea, and terminal deoxynucleotidyl transferase- mediated dUTP- biotin nick end labeling (TUNEL)-stained positive cells in animals treated with gentamicin. However, pretreatment with S. miltiorrhiza (3g/kg/day for 10 days) decreased gentamicin-induced hearing loss, attenuated iNOS and caspase-3 expression, and decreased the number of apoptotic cells. Furthermore, it also reduced the ultrastructural damage due to ototoxicity as observed by SEM and TEM.
These findings indicate that S. miltiorrhiza protects against gentamicin-induced ototoxicity and could apply to the protection of ototoxicity.
由于氨基糖苷类抗生素具有耳毒性副作用，其在大多数国家的临床应用受到限制。然而，在发展中国家它们的使用很普遍，因为其价格低廉且使用方便。丹参提取物因其抗氧化特性在中国临床上被使用。我们研究了临床批准的丹参注射液对氨基糖苷类抗生素庆大霉素诱导的诱导型一氧化氮合酶（iNOS）生成的影响以及耳毒性保护机制。
本研究使用了60只成年豚鼠，分为四组。在治疗前后进行听性脑干反应（ABR）测试，在确定ABR阈值变化后处死动物进行形态学和免疫染色分析。通过透射电子显微镜（TEM）和扫描电子显微镜（SEM）检查耳蜗，以观察超微结构变化。此外，测量毛细胞损失、iNOS和半胱天冬酶 - 3表达以及细胞凋亡情况。
结果显示，用庆大霉素治疗的动物出现听力损失、耳蜗中iNOS过表达并伴有结构紊乱，以及末端脱氧核苷酸转移酶介导的dUTP - 生物素缺口末端标记（TUNEL）染色阳性细胞。然而，用丹参（3g/kg/天，共10天）预处理可减少庆大霉素诱导的听力损失，减弱iNOS和半胱天冬酶 - 3表达，并减少凋亡细胞数量。此外，如SEM和TEM所观察到的，它还减少了耳毒性引起的超微结构损伤。
这些发现表明丹参可预防庆大霉素诱导的耳毒性，可应用于耳毒性的保护。
