咪康唑对大鼠缺氧缺血性早产儿脑白质损伤的保护作用

Protective effect of miconazole on white matter damage induced by anoxia and ischemia in rats

目的探讨咪康唑对早产儿脑白质损伤(WMD)大鼠髓鞘的保护作用。方法新生3日龄SD大鼠随机分为假手术组、WMD模型组、10 mg/(kg·d))和40 mg/(kg·d)咪康唑组,每组15只;采用结扎右侧颈总动脉,缺氧80 min的方法制作早产儿WMD模型。咪康唑组于建模后第1~5天腹腔注射10 mg/(kg·d)和40 mg/(kg·d)咪康唑,WMD模型组注射等浓度二甲基亚砜(DMSO)。采用髓鞘碱性蛋白(MBP)免疫荧光染色及Western blot检测脑白质特异性MBP表达量,超微结构电镜观察髓鞘超微结构变化,并比较各组幼鼠体质量变化。结果 WMD大鼠经咪康唑治疗后,胼胝体MBP表达量较WMD模型组高,差异有统计学意义(P<0.05)。咪康唑治疗组MBP的表达量较模型对照组增高。模型对照组胼胝体髓鞘疏松,髓鞘内小空泡形成,呈筛网状改变,髓鞘厚度明显降低,结构紊乱。经咪康唑治疗后可明显改善缺氧缺血所致的脱髓鞘改变。WMD模型组幼鼠体质量增长速度较假手术组明显减慢,咪康唑治疗后大鼠的体质量生长速度增快。结论咪康唑可通过促进髓鞘形成保护新生大鼠脑缺氧缺血诱导的白质损伤,并改善大鼠的生长发育情况。

ObjectiveTo explore the protective effect of miconazole on white matter damage （WMD） in neonatal rats. MethodsThree-day-old neonatal SD rats were randomly divided into sham group, WMD model group, 10 mg/（kg·d） miconazole group and 40 mg/（kg·d） miconazole group with 15 rats each. Rats in WMD model group were subjected to the ligation of right carotid artery, and then kept in a chamber with 6% oxygen and 94% nitrogen for 80 min to establish the white matter damage model. The rats in miconazole group were intraperitoneally injected with different doses （10 and 40mg/kg） of miconazole, dissolved in dimethyl sulfoxide （DMSO）, for fve consecutive days, and rats in WMD model group were injected with the same volume of DMSO. Myelin basic protein （MBP） of white matter was detected by immunofuorescence staining and western blot. Myelin sheaths of corpus callosum were observed by transmission electron microscopy. Weight changes of rats were compared among groups. ResultsImmunofuorescence staining and western blot showed that, after treatment with miconazole, the MBP expression level of corpus callosum was higher than in WMD model group （P〈0.05）. In WMD model group, the myelin sheath of corpus callosum had loose structure and a large number of small vacuoles with decreased thickness of myelin sheath. After treatment with miconazole, myelinolysis induced by anoxia and ischemia could be improved signifcantly. The increase in weight of rats in WMD model group was signifcantly less than that in sham group. And after miconazole treatment, the rate of weight gain of rats was increased. ConclusionMiconazole can signifcantly reduce the brain white matter damage induced by anoxia and ischemia through promoting myelination, and then improves the growth and development in rats.