年龄相关性听力减退大鼠听觉神经通路形态学和相关蛋白质组学初步研究
摘要
目的:本实验在3月龄、18月龄大鼠听觉神经通路形态学研究的基础上,旨在通过对不同年龄大鼠蜗核、听皮层组织蛋白质组的差异分析,初步探讨年龄相关性听力减退大鼠听觉神经通路蛋白质水平的变化,为进一步确定听觉老化相关蛋白打下基础。
方法:①通过脑干电反应测听(ABR),乙酰胆碱酯酶染色耳蜗基底膜铺片,蜗核、听皮层石蜡切片甲苯胺兰染色等方法分别对3月及18月龄大鼠(各10只)8KHz听阈,耳蜗、蜗核、听皮层形态进行对比研究。②应用双向凝胶电泳分离技术(2—DE)、质谱技术(MS),对3月及18月龄大鼠蜗核及听皮层组织进行蛋白质组差异分析。③应用免疫组化技术验证已鉴定的差异蛋白质点。
结果:①ABR检测显示3月龄和18月龄大鼠8KHz听阈分别为14.5±2.84dBSPL和33.5±4.12dBSPL,差异有显著性(P＜0.01)。②形态学研究发现18月龄大鼠耳蜗底回传出神经末梢较3月龄大鼠减少36%,缺失以2、3排外毛细胞为主。耳蜗核神经元数量较3月龄大鼠减少24%,但听皮层神经元数量无明显差异。③蛋白质组差异分析显示:3月龄和18月龄大鼠蜗核、听皮层组织蛋白质组间存在差异,经肽质指纹图谱(PMF)分析初步鉴定了醛缩酶C、γ—氨基丁酸转氨酶、内质网蛋白29、蛋白二硫化异构酶A3、亮氨酸氨基肽酶、NAD依赖性去乙酰基转移酶、神经胶质纤维酸性蛋白、甘油醛—3—磷酸脱氢酶、NADH脱氢酶1α亚复合体10、二氢蝶啶还原酶、谷氨酸脱氢酶、confilin-1和Nipsnap1 13个蛋白质。这些蛋白质可能与听觉系统的老化相关。④通过对已鉴定蛋白质——NAD依赖性去乙酰基转移酶(SirT2)的免疫组化验证,证实该蛋白质在18月龄大鼠蜗核中表达下降。
结论:①18月龄大鼠听觉神经通路已有明显老化。②3月龄大鼠和18月龄大鼠蜗核、听皮层组织蛋白质组间存在差异,这些差异表达蛋白质可能与年龄相关性听力减退有关。
Objective:The study was to explore the age-related hearing impairment related to morphology and proteomics in the auditory neuropathway in Wistar rats,through morphological study and proteomics in the auditory cortex and the cochlear nuclei in the three-month-old rats and the eighteen-month-old rats.
Methods:①Auditory brainstem response(ABR)was assessed in the three-month-old rats and the eighteen-month-old rats.Cochlear acetycholinesterase staining,Cochlear nuclei and auditory cortex neurons Toluidine blue staining were used in the morphological study.②Two-dimensional gel electrophoresis(2-DE)and Mass spectrometry(MS)were used to detect the difference proteins in the auditory cortex and the cochlear nuclei between the three-month-old rats and the eighteen-month-old rats.③Immunohistochemistry was used to validate the difference proteins.
Result:①ABR threshold in the eighteen-month-old rats (33.5±4.12dBSPL)was significantly increased,compared with that in the three-month-old rats(14.5±2.84dBSPL)(P＜0.01).②Cochlear acetycholinesterase staining showed that the density of efferent nerve endings in the basal turn is less 36%in the eighteen-month-old rats relative to the three-month-old rats,and the loss of never endings was found mostly at the second and the third row of outer hair cells.③The number of neurons of the cochlear nuclei in the eighteen-month-old rats were less 24%than the three-month-old rats.However,the distribution of neuron in the auditory cortex was not markedly changed in two groups.④The differences in protein expression in the auditory cortex and the cochlear nuclei between the three-month-old rats and the eighteen-month-old rats were found,by means of identification of protein spots from 2-DE gels. 13 peptide mass fingerprints(PMF)maps were obtained by MALDI-TOF-MS,and Fructose-bisphosphate aldolase C,Gama-aminobutyrate aminotransferase,Endoplasmic reticulum protein 29,Disulfide isomerase associated 3,NAD-dependent deacetylase sirtuin-2,Leucine aminopeptidase 3,Dihydropteridine reductase(with NADH),Ndufa10 protein,glial fibrillary acidic proteins,Cofilin-1,glutamate dehydrogenase [NAD(P)],Dihydrolipoamide dehydrofenase,Nipsnap1protein(Fragment), Glyceradehyde-3-phosphate dehydrogenase were identified.⑤The immunohistochemical study demonstrated that SirT2 expression in the cochlear nuclei of the eighteen-month-old rats were decreased.
CONCLUSION:①Auditory neuropathway of the eighteen-month-old rats had been significantly degenerated.②The differences in the protein expression in the auditory cortex and the cochlear nuclei between the three-month-old rats and the eighteen-month-old rats were found,which may be related to age-related heating impairment.
方法:①通过脑干电反应测听(ABR),乙酰胆碱酯酶染色耳蜗基底膜铺片,蜗核、听皮层石蜡切片甲苯胺兰染色等方法分别对3月及18月龄大鼠(各10只)8KHz听阈,耳蜗、蜗核、听皮层形态进行对比研究。②应用双向凝胶电泳分离技术(2—DE)、质谱技术(MS),对3月及18月龄大鼠蜗核及听皮层组织进行蛋白质组差异分析。③应用免疫组化技术验证已鉴定的差异蛋白质点。
结果:①ABR检测显示3月龄和18月龄大鼠8KHz听阈分别为14.5±2.84dBSPL和33.5±4.12dBSPL,差异有显著性(P＜0.01)。②形态学研究发现18月龄大鼠耳蜗底回传出神经末梢较3月龄大鼠减少36%,缺失以2、3排外毛细胞为主。耳蜗核神经元数量较3月龄大鼠减少24%,但听皮层神经元数量无明显差异。③蛋白质组差异分析显示:3月龄和18月龄大鼠蜗核、听皮层组织蛋白质组间存在差异,经肽质指纹图谱(PMF)分析初步鉴定了醛缩酶C、γ—氨基丁酸转氨酶、内质网蛋白29、蛋白二硫化异构酶A3、亮氨酸氨基肽酶、NAD依赖性去乙酰基转移酶、神经胶质纤维酸性蛋白、甘油醛—3—磷酸脱氢酶、NADH脱氢酶1α亚复合体10、二氢蝶啶还原酶、谷氨酸脱氢酶、confilin-1和Nipsnap1 13个蛋白质。这些蛋白质可能与听觉系统的老化相关。④通过对已鉴定蛋白质——NAD依赖性去乙酰基转移酶(SirT2)的免疫组化验证,证实该蛋白质在18月龄大鼠蜗核中表达下降。
结论:①18月龄大鼠听觉神经通路已有明显老化。②3月龄大鼠和18月龄大鼠蜗核、听皮层组织蛋白质组间存在差异,这些差异表达蛋白质可能与年龄相关性听力减退有关。
Objective:The study was to explore the age-related hearing impairment related to morphology and proteomics in the auditory neuropathway in Wistar rats,through morphological study and proteomics in the auditory cortex and the cochlear nuclei in the three-month-old rats and the eighteen-month-old rats.
Methods:①Auditory brainstem response(ABR)was assessed in the three-month-old rats and the eighteen-month-old rats.Cochlear acetycholinesterase staining,Cochlear nuclei and auditory cortex neurons Toluidine blue staining were used in the morphological study.②Two-dimensional gel electrophoresis(2-DE)and Mass spectrometry(MS)were used to detect the difference proteins in the auditory cortex and the cochlear nuclei between the three-month-old rats and the eighteen-month-old rats.③Immunohistochemistry was used to validate the difference proteins.
Result:①ABR threshold in the eighteen-month-old rats (33.5±4.12dBSPL)was significantly increased,compared with that in the three-month-old rats(14.5±2.84dBSPL)(P＜0.01).②Cochlear acetycholinesterase staining showed that the density of efferent nerve endings in the basal turn is less 36%in the eighteen-month-old rats relative to the three-month-old rats,and the loss of never endings was found mostly at the second and the third row of outer hair cells.③The number of neurons of the cochlear nuclei in the eighteen-month-old rats were less 24%than the three-month-old rats.However,the distribution of neuron in the auditory cortex was not markedly changed in two groups.④The differences in protein expression in the auditory cortex and the cochlear nuclei between the three-month-old rats and the eighteen-month-old rats were found,by means of identification of protein spots from 2-DE gels. 13 peptide mass fingerprints(PMF)maps were obtained by MALDI-TOF-MS,and Fructose-bisphosphate aldolase C,Gama-aminobutyrate aminotransferase,Endoplasmic reticulum protein 29,Disulfide isomerase associated 3,NAD-dependent deacetylase sirtuin-2,Leucine aminopeptidase 3,Dihydropteridine reductase(with NADH),Ndufa10 protein,glial fibrillary acidic proteins,Cofilin-1,glutamate dehydrogenase [NAD(P)],Dihydrolipoamide dehydrofenase,Nipsnap1protein(Fragment), Glyceradehyde-3-phosphate dehydrogenase were identified.⑤The immunohistochemical study demonstrated that SirT2 expression in the cochlear nuclei of the eighteen-month-old rats were decreased.
CONCLUSION:①Auditory neuropathway of the eighteen-month-old rats had been significantly degenerated.②The differences in the protein expression in the auditory cortex and the cochlear nuclei between the three-month-old rats and the eighteen-month-old rats were found,which may be related to age-related heating impairment.
引文
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