关键词: 内质网应激, 糖尿病,实验性, 耳蜗毛细胞, 细胞凋亡

Abstract: Objective: To investigate the influence of endoplasmic reticulum stress (ERS) in the degeneration of cochlear hair cells in the type 2 diabetic mice, and to clarify its mechanism.Methods: Twenty clean Kun Ming male mice aged one month were selected and randomly divided into control group and model group(n=10).The mice in model group were injected with STZ (40 mg·kg^-1) to establish the type 2 diabetic models. The fasting blood glucose levels of the mice were measured through collecting the vena caudalis blood of the mice. Auditory brain stem response(ABR) was used to detect the ABR threshold of the mice. Otoacoustic emission (OAE) test was used to detect the OAE threshold of mice. The defect rate of mouse cochlear outer hair cells was calculated by the mouse cochlear spreading technique. The expression levels of GRP78, caspase-12, p-ERK and Nrf2 proteins were detected by Western blotting method.Results: Compared with control group, the fasting blood glucose levels of the mice in model group at the 7th and the 14th days had no significant differences(P>0.05), but the levels were increased significantly at the 21th, 28th and 35th days and the level reached the highest value at the 35th day. The ABR thresholds of the mice in model group at 8,12,and 24 kHZ were increased significantly compared with control group(P<0.05). Under the stimulation of low frequency, there was no significant change in the OAE threshold of the mice in model grouop compared with control group. The OAE thresholds of the mice in model group were increased significantly under the medium frequency and high frequency stimulation compared with control group(P<0.05).The defects of the cochlear hair cells were mainly concentrated on the bottom of gyrus of the mice,and the defects in middle temporal gyrus and parietal gyrus were less.Compared with control group,the defect rate in the bottom of gyrus of the mice in model group was increased significantly(P<0.05);the defect rates in the middle temporal gyrus and parietal gyrus were increased,but there was no significant difference(P>0.05). The expression levels of p-ERK and Nrf2 in the cochlear hair cells of the mice in model group were lower than those in control group(P<0.05), and the expression levels of GRP78 and caspase-12 were higher than those in control group(P<0.05).Conclusion: ERS can result in the increase of defect rate of cochlear outer hair cells and ABR brainstem hearing threshold of the diabetic mice and decrease the expression levels of p-ERK and Nrf2 proteins, suggesting that ERS can promote the degenerative lesions of cochlear hair cells in the type 2 diabetic mice.

Key words: endoplasmic reticulum stress, diabetes mellitus,experiment, cochlear hair cells, apoptosis