Objective To study the unfolded protein glucose-regulated protein 78 (GRP78) expression level after intense noise exposure,and to find out the relationship between UPR and the intense noise induced cochlea cell damage. Methods Forty-eight guinea pigs were randomly divided into 6 groups(8 guinea pigs/group). The guinea pigs in the experiment groups were exposed to 4 kHz narrow band noise at 120 dB SPL for 4 housr while aninals in control group received no noise exprsure. Auditory brainstem response(ABR) of the guinea pigs in experiment and control groups were tested at 3 hours, 1, 4, 14,30 days post noise exposure. Four guinea pig's cochleas from each group were used for paraffin sectioning, and the rest was used for the total protein extraction. Expression of Bip/GRP78 was studied by immunohistochemistry sectioning and western blot. Results There were significantly higher expressions of Tunel-Positve cells in the OHC,SGC and SV in experiment groups compared with those in the controi group (P＜0.01). Protein levels of Bip/GRP78 were significantly increased after noise exposure compared with those in the control group (P＜0.01). Conclusion After intense noise exposure, UPR protection mechanisms were initiated and by upregulating the expression of molecular chaperones Bip/GRP78, folded proteins were correctly guided, thus reducing cell damage. This may be one of the endogenous protective mechanisms in the guinea pig cochlea.%目的 探讨未折叠蛋白反应(unfolded protein response,UPR)标志物葡萄糖调节蛋白78(Bip/GRP78)在强噪声致豚鼠耳蜗细胞损伤中的作用.方法 48只豚鼠随机分为6组,分别为健康对照组(不给噪声暴露)和强噪声暴露后3 h、1 d、4 d、14 d、30 d组,每组8只,噪声暴露的5组豚鼠在120 dB SPL、4 kHz窄带噪声环境暴露4 h后,各组豚鼠于相应时间点处死前及对照组均测试听性脑干反应(ABR),然后每组各取4只豚鼠耳蜗作石蜡切片,余4只豚鼠提取耳蜗总蛋白.用免疫组化及Western Blot方法检测Bip/GRP78的表达及其在耳蜗的分布.结果 强噪声暴露后各组Bip/GRP78蛋白表达明显高于正常组,且各时间点都维持在比较高的水平,Bip/GRP78蛋白在噪声暴露后各组豚鼠耳蜗的内外毛细胞、螺旋神经节细胞、侧壁细胞均有表达.结论 强噪声暴露后,启动UPR保护机制,通过上调分子伴侣Bip/GRP78的表达,引导蛋白质正确折叠,降低细胞损伤,可能是耳蜗内源性保护机制之一.
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