Jang Chul Ho, Cho Yong Beom, Choi Cheol Hee, Jang Yoon Seok, Jang Sook Jin, Jung Won-Kyo, Park Byung Young, Kim Min Young
Department of Otolaryngology, Chonnam National University Medical School, Gwangju, South Korea; Research Center for Resistant Cells, Chosun Medical School, Gwangju, South Korea.
Department of Otolaryngology, Chonnam National University Medical School, Gwangju, South Korea.
Int J Pediatr Otorhinolaryngol. 2014 Mar;78(3):465-70. doi: 10.1016/j.ijporl.2013.12.022. Epub 2013 Dec 27.
To assess whether this compound (ALH-L1005) is conceivably an effective agent in protecting against cochlear damage induced by LPS.
Tube formation using human umbilical vein endothelial cell (HUVEC) and matrix metalloproteinase (MMP)-9 inhibition assay was performed. 24 guinea pigs were randomly divided into three groups. Intratympanic instillation of LPS (n=8) as negative control, instillation of oxytetracycline 1h after LPS as positive control (n=8), and intratympanic instillation of ALH-L1005 (n=8) 1h after LPS were considered experimental group. Evaluation by auditory brainstem response (ABR) measurement, cochlear blood flow, and blood-labyrinth barrier (BLB) permeability were performed. Cochlear hair cells were observed by field emission-scanning electron microscopy (FE-SEM). MMP-9 activation was measured by gelatin zymography.
For HUVEC, the tube formation was suppressed in a dose dependant manner. ALH-L1005 inhibited the MMP-9 activity prominently. It also attenuated the elevation of LPS-induced hearing threshold shift and recovery of CBF. By FE-SEM, cochlear hair cells could be preserved in experimental group. ALH-L1005 significantly reduced the BLB opening compared to LPS group. Active MMP-9 expression could be detected in the LPS group. In contrast to ALH-L1005 group, active MMP-9 expression was not detected.
Our results conclude that ALH-L1005 showed a protective effect in the cochlear lateral wall damage induced by LPS.
评估该化合物(ALH-L1005)是否可能是预防脂多糖(LPS)诱导的耳蜗损伤的有效药物。
进行了使用人脐静脉内皮细胞(HUVEC)的管形成实验和基质金属蛋白酶(MMP)-9抑制实验。24只豚鼠随机分为三组。鼓膜内滴注LPS(n = 8)作为阴性对照,LPS滴注1小时后滴注土霉素作为阳性对照(n = 8),LPS滴注1小时后鼓膜内滴注ALH-L1005(n = 8)作为实验组。通过听性脑干反应(ABR)测量、耳蜗血流和血迷路屏障(BLB)通透性进行评估。通过场发射扫描电子显微镜(FE-SEM)观察耳蜗毛细胞。通过明胶酶谱法测量MMP-9激活情况。
对于HUVEC,管形成呈剂量依赖性抑制。ALH-L1005显著抑制MMP-9活性。它还减轻了LPS诱导的听力阈值升高和CBF的恢复。通过FE-SEM,实验组的耳蜗毛细胞得以保存。与LPS组相比,ALH-L1005显著减少了BLB开放。在LPS组中可检测到活性MMP-9表达。与ALH-L1005组相比,未检测到活性MMP-9表达。
我们的结果表明,ALH-L1005对LPS诱导的耳蜗侧壁损伤具有保护作用。