地塞米松鼓室内注射后在大鼠耳蜗中的分布  

Distribution of dexamethasone in cochlea after intratympanic injection in rats

作　　者：傅窈窈[1] 张天宇[1] 赵晖[1] 李雯[1] 

机构地区：[1]复旦大学附属眼耳鼻喉科医院耳鼻咽喉头颈外科,上海200031

出　　处：《中华耳鼻咽喉头颈外科杂志》2009年第3期237-241,共5页Chinese Journal of Otorhinolaryngology Head and Neck Surgery

基　　金：上海市浦东新区社会发展局卫生科技资助项目（PW2008D-3）

摘　　要：目的观察不同浓度地塞米松鼓室内注射后在大鼠耳蜗中的分布及代谢规律。方法144只sD大鼠全麻下鼓室内分别注射5mg／ml、10mg／ml和20mg／ml地塞米松磷酸钠，并分别于注射后5min、10min、15min、30rain、1h、2h、4h、8h、12h、24h、48h及72h处死动物，每个浓度、每个时间点4只大鼠。耳蜗标本处理后冰冻切片，免疫荧光法观察地塞米松在耳蜗组织中随时间的变化情况，并进行荧光半定量分析。另取4只正常SD大鼠采用免疫荧光方法观察糖皮质激素受体在耳蜗内的分布。结果地塞米松自注射后15min起在耳蜗内始被检测到，30min达到高峰，主要分布在螺旋韧带，Corti器和螺旋神经节。10mg／ml组与20mg／ml组各时间点的地塞米松浓度均高于5mg/ml组，持续时间亦从低浓度组的48h延长至72h。糖皮质激素受体亦主要分布于Corti器，螺旋神经节和螺旋韧带。结论地塞米松鼓室内注射后可迅速到达耳蜗组织细胞中，其分布与糖皮质激素受体基本一致。增加地塞米松浓度可以提高其在耳蜗组织中的分布浓度，并延长其存留时间。Objective To investigate the distribution and pharmacokinetics of dexamethasone of different concentrations in the inner ears of SD rats after intratympanic injection. Methods Totally 144 adult SD rats were anaesthetized and dexamethasone sodium phosphate of different concentrations（5 mg/ml, 10 mg/ml, 20 mg/ml） was injected into the tympanums. The rats were sacrificed at various postinjection survival times （5 min, 10 min, 15 min, 30 rain, 1 h, 2 h, 4 h, 8 h, 12 h, 24 h, 48 h, 72 h） ,and every 4 rats were included into each group. Then after a series of processes the inner ear tissue was cryostat sectioned. The distribution of dexamethasone was evaluated using immunofluorescence with semiquantitative analysis. Immunofluorescence was also used in another 4 normal SD rats to detect the distribution of Glucocorticoid receptor （GR） in the inner ear. Results Dexamethasone was observed initially 15 min after local drug administration and 30 min to its peak level. The highest concentration of dexamethasone labeling was seen in the spiral ligament, organ of Corti and spiral ganglion, which paralleled the distribution of GR. The tissue concentration of 10 mg/ml and 20 mg/ml groups was higher than 5 mg/ml every corresponding time point, and the lasting time was also prolonged from 48 hours to 72 hours. Conclusions Dexamethasone can enter into the cochlear tissue quickly after transtympanic injection, and its distribution accords nearly exactly with that of GR. Increase of the concentration of dexamethasone results in higher tissue distribution and longer lasting time.

关 键 词：地塞米松 受体 糖皮质激素 耳蜗 组织分布 大鼠 

分 类 号：R686[医药卫生—骨科学]