Department of Otorhinolaryngology, Faculty of Medicine, Sanko University, Incilipinar Mah. Ali Fuat Cebesoy Bulv. No: 45, Gaziantep, Turkey.
Department of General Surgery, Faculty of Medicine, Sanko University, Gaziantep, Turkey.
Eur Arch Otorhinolaryngol. 2019 Jul;276(7):1921-1931. doi: 10.1007/s00405-019-05417-5. Epub 2019 Apr 6.
The aim of this study was to investigate the potential protective and therapeutic effects of milrinone, a specific phosphodiesterase (PDE) III inhibitor, on acoustic trauma-induced cochlear injury and apoptosis.
A total number of 30 healthy Wistar albino rats were evenly divided into five groups as follows: group 1 was assigned as control group; group 2 and 3 were assigned as low-dosage groups (0.25 mg/kg) in which milrinone was administered 1 h before acoustic trauma (AT) and 2 h after AT, respectively; group 4 and 5 were assigned as high-dosage groups (0.50 mg/kg) in which the drug was administered 1 h before AT and 2 h after AT, respectively. Except control group, all treatment groups received a single dosage of milrinone for 5 days. Distortion product otoacoustic emissions (DPOAE) measurements were recorded before AT as well as at second and fifth post-traumatic days. At the end of fifth day, all rats were sacrificed and the cochlea of the rats was removed for histopathological evaluation. In addition, the groups were compared in terms of apoptotic index via caspase-3 staining.
In terms of signal-to-noise ratio (SNR), there was no statistically significant difference among the groups following AT (p > 0.05). After 5 days of milrinone treatment, the best SNR values were found in group 5, though all groups did not statistically differ (p > 0.05). In histopathological evaluation, vacuolization, inflammation, and edema scores in all treatment groups were statistically lower than those of the control group (p < 0.05). In group 2 and 4 where the drug was administered before AT, the inflammation and apoptosis index was lower than those of group 3 and 5 where the drug was administered after AT (p < 0.0001).
We reveal that milrinone has a protective effect on cochlear damage in the experimental acoustic model of rats. This protective effect was more apparent following the pre-traumatic milrinone administration, and is associated with its effect on decreasing inflammation and apoptosis. Based on DPOAE measurements following AT, especially in the group 5 (high-dosage group), milrinone may also have a therapeutic effect.
本研究旨在探讨米力农，一种特定的磷酸二酯酶（PDE）III 抑制剂，对声创伤诱导的耳蜗损伤和细胞凋亡的潜在保护和治疗作用。
将 30 只健康的白化 Wistar 大鼠平均分为五组：第 1 组为对照组；第 2 组和第 3 组为低剂量组（0.25mg/kg），米力农分别在声创伤（AT）前 1 小时和 AT 后 2 小时给药；第 4 组和第 5 组为高剂量组（0.50mg/kg），药物分别在 AT 前 1 小时和 AT 后 2 小时给药。除对照组外，所有治疗组均接受为期 5 天的单次剂量米力农治疗。在 AT 前以及 AT 后第 2 天和第 5 天记录畸变产物耳声发射（DPOAE）测量值。在第 5 天结束时，所有大鼠被处死，取出大鼠耳蜗进行组织病理学评估。此外，通过 caspase-3 染色比较各组的细胞凋亡指数。
在信噪比（SNR）方面，AT 后各组之间没有统计学差异（p＞0.05）。在米力农治疗 5 天后，发现第 5 组的 SNR 值最佳，但所有组之间没有统计学差异（p＞0.05）。在组织病理学评估中，所有治疗组的空泡化、炎症和水肿评分均明显低于对照组（p＜0.05）。在 AT 前给予药物的第 2 组和第 4 组，炎症和细胞凋亡指数低于 AT 后给予药物的第 3 组和第 5 组（p＜0.0001）。
我们发现米力农对大鼠实验性声创伤模型中的耳蜗损伤具有保护作用。这种保护作用在创伤前给予米力农时更为明显，与减少炎症和细胞凋亡有关。根据 AT 后 DPOAE 测量值，尤其是在第 5 组（高剂量组），米力农可能具有治疗作用。
