Geranylgeranylacetone, a heat shock protein inducer, prevents acoustic injury in the guinea pig
Geranylgeranylacetone, a heat shock protein inducer, prevents acoustic injury in the guinea pig
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DOI：
10.1016/j.brainres.2005.10.045
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发表时间：
2005-12-14
期刊：
影响因子：
2.9
通讯作者：
Yamashita, H
中科院分区：
文献类型：
--
作者：
Mikuriya, T;Sugahara, K;Yamashita, H
香叶基香叶基丙酮（GGA）是胃粘膜、肝、心、脑等组织热休克蛋白（Hsps）的诱导剂，广泛用作抗溃疡剂。然而，GGA是否能诱导耳蜗Hsps产生耳保护作用尚未见报道。本研究旨在探讨单次口服GGA是否能诱导耳蜗Hsps的产生，以及GGA对噪声损伤耳蜗是否具有保护作用。Ale使用Hartley豚鼠，通过Western blot分析研究了Hsp 70、40和27在耳蜗中的表达。为了评估耳蜗功能，我们评估了听觉脑干反应（ABR）的阈值。组织学检查采用表面制备技术观察感觉上皮。经口给予动物GGA（600 mg/kg）或溶媒。Western blot分析显示，单剂量GGA给药后24-48 h，Hsp 70、40和27的表达增加，而给予溶剂的动物中表达较少。在噪声暴露（130 dB SPL倍频程手噪声，中心频率为4 kHz）前，每天给予GGA一次，持续一周，持续3 h。ABR阈值升高明显降低。此外，GGA处理的动物中Corti器外毛细胞上观察到的缺陷显著少于未处理的动物。这一结果表明，GGA预处理有可能预防强噪声对耳蜗的损伤。(C)2005 Elsevier B. V.保留所有权利。
Geranylgeranylacetone (GGA) used widely as anti-ulcer agent is accepted as an inducer of the heat shock proteins (Hsps) at gastric mucosa, liver, heart, and brain. However, there have been no reports that GGA could induce Hsps in the cochlea leading up to the oto-protection. The purpose of the present Study was to investigate whether single oral dose of GGA could induce Hsps at cochlea and oral administration had protective effect to the cochlea against noise trauma. Ale used Hartley guinea pigs and investigated the expression of Hsp70, 40, and 27 in cochlea by Western blot analysis. To evaluate cochlear function, we assessed thresholds of the auditory brain stein response (ABR). For histological assessment, we observed the sensory epithelium Using surface preparation technique. GGA (600 mg/kg) or vehicle was given orally to animals. Western blot analysis showed that the expressions of Hsp 70, 40, and 27 were increased 24-48 h after administration of single dose of GGA, whereas there was less expression in the animals given vehicle. In the animals given GGA once a day for a week before sound exposure (130 dB SPL octave hand noise with a center frequency of 4 kHz) for 3 h. their ABR threshold elevations were lowered significantly. In addition, significantly fewer defects were observed on outer hair cells of organ of Corti in the animals treated by GGA than those of the animals without GGA. This result shows that pretreatment by GGA have a potential to prevent cochlea damage against the intense noise. (C) 2005 Elsevier B.V. All rights reserved.