丹参注射液对豚鼠耳蜗毛细胞的影响

Effects of Salvia Miltiorrhizae injection on acid phosphatase in the cochlear hair cell of the guinea pigs

目的观察丹参注射液对豚鼠庆大霉素耳中毒引起的耳蜗毛细胞酸性磷酸酶变化的影响。方法选用耳廓反射正常,体重250g～300g的健康杂色豚鼠,雌雄不限,随机分成3组,正常对照组15只,肌肉注射生理盐水2ml/(kg·d)；庆大霉素组15只,肌肉注射庆大霉寨80mg／(kg·d)；丹参注射液组15只,腹腔注射丹参注射液6mg／(kg·d),然后肌肉注射庆大霉素同庆大霉素组。各组动物连续注射药物均20天。用脑干听觉诱发电位(auditory brainstem response audiometry,ABR)检查豚鼠的听阈变化情况；用组织化学方法检测耳蜗毛细胞酸性磷酸酶的变化情况。结果正常对照组、庆大霉素组和丹参注射液组动物的ABR阈值分别为：(34.50±1.22)dB peSPL、(34.25±1.18)dBpeSPL和(34.39±1.27)dB peSPL；用药后第22天,反应阈值分别为：(34.65±1.32)dB peSPL、(71.25±24.73)dB peSPL和(41.05±10.93)dB peSPL。对照组分别与庆大霉素、丹参注射液组比较,差异显著(t=8.097,3.184,P＜0.01)；丹参注射液组与庆大霉察组比较,有显著性差异(t=6.118,P＞0.01)。耳蜗铺片光镜下观察毛细胞酸性磷酸酶染色：正常对照组呈棕褐色,显色分布均匀,毛细胞排列整齐；庆大霉素组毛细胞依动物耳聋程度不同而出现不同程度染色缺失,庆大霉素组染色缺失显著,丹参注射液组染色缺失轻,两组比较有明显差异。结论丹参注射液能明显降低庆大霉素的耳毒性；保护耳蜗毛细胞溶酶体的完整性,降低庆大霉素对溶酶体的损坏而造成的毛细胞自溶性损伤,是丹参注射液降低庆大霉索耳毒性的机制之一。

OBJECTIVE The purpose of this study was to investigate the effects of SM on acid phosphatase （ACP） in the cochlear hair cell of the guinea pigs with ototoxicity induced by Gentamicin （GM） .METHODS Healthy mottle guinea pigs with normal auricle reflex （250g to 300g in body mass , male or female） were randomly divided into 3 groups of fifteen each ：Control group, in which physiological saline （2 ml / kg·d） was jnjected intramuscularly ; GM group, in which gentamicin （80mg/kg·d）was injected intramuscularly ; SM group, in which gentamicin was injected as same as the GM group after SM （ 6 mg / kg·d ）being injected intraabdominally.All the three groups were adminstrated for 20 days.The changes of auditory reaction threshold and ACP in the cochlear hair cells were detected by brainstem auditory evoked potential （ABR） and histochemistry respectively.RESULTS The thresholds of ABR reaction in the control group, the GM group and the SM group before administration were 34.50±1.224, 34.25±1.175, 34.39±1.272 （dB peSLP） respectively, and were 34.65±1.321, 71.25±24.73, 41.05±10.930 （dB peSLP） 22-day after adminstration. There was a significant difference between control group and GM group, and SM group （t=8.097, 3.184, P〈0.01）; There was a significant difference between SM group and GM group（t=6.118, P〉0.01）. The changes of the ACP in the cochlear hair cells： a purple-blue color of ACP histochemical staining could be observed with the light microscope in the cochlear basal membrane of contral group and the hair cells were arranged in good order and were even in color .The ACP staining loss was found in cochlear hair cells of GM group; there was a light ACP staining loss in SM group. A significant difference was found between the two groups.CONCLUSION The modified SM can reduce genetamicin ototoxicity.The mechanism of modified SM effect may be associated with the protection of the integrity of lysosome and the reduction of autolysis induced by hydrolase overflowing from lysosome in the hair cells.