褪黑素对缺氧缺血所致的未成熟脑白质损伤大鼠的干预作用

Role of melatonin for repairing the periventricular white matter damage due to hypoxia-ischemia in the developing brain of rat

目的 探讨褪黑素对缺氧缺血损伤后的未成熟脑白质的干预作用及其可能机制.方法 48只3日龄SD大鼠随机数字表法分为假手术组（SHAM组）、缺氧缺血组（HI组）和褪黑素干预组（MT组）.参照Rice模型制作脑室周围白质损伤（PWMD）动物模型,MT组分别于术前、术后、术后1h及术后24 h按10 mg/kg腹腔注射褪黑素溶液,SHAM组、HI组则在相同时间点腹腔注射等体积溶剂.分别于术后2d、14 d处死大鼠,断头取脑,应用HE染色、免疫组织化学法染色观察鼠脑脑室周围白质.结果 术后2d3组大鼠脑室周围白质组织学结构区别明显,O4阳性细胞数目在SHAM组[（75.548±7.333）/hpf]、MT组[（59.971±3.635）/hpf]、HI组[（40.511±2.848）/hpf]依次减少,差异有统计学意义（P＜0.05）;Caspase-3的表达在SHAM组（107.724±10.266）、MT组（132.289±8.537）、HI组（202.168±14.367）依次增加,差异有统计学意义（P＜0.05）;术后14 d大鼠手术侧脑室指数在SHAM组（0.928±0.063）、MT组（1.813 ±0.110）、HI组（2.752±0.201）依次增大,髓鞘碱性蛋白（MBP）吸光度值则依次减少,分别为39.504±1.673,21.729±1.614,11.344±1.118.结论 MT可能通过抑制少突胶质细胞前体的凋亡对未成熟大鼠脑PWMD发挥保护作用.

Objective To investigate the protective effect of melatonin and its possible mechanism for repairing in the immature white matter damage due to brain hypoxia-ischemia （HI）.Methods Forty-eight three-day SD rats after birth were randomly divided into 3 groups：sham-operated（SHAM） group,HI group and melatonin treatment（MT） group.Periventricular white matter damage （PWMD） to animal models were estabished according to Rice modeling.MT group was treated with melatonin pre-operatively,immediately postoperation,1 hour postoperation and 24 hours postoperation via intraperitoneal injection,and the other groups were injected with the same volume of dissolvent.The rats were executed by decollation after 2 days and 14 days.The histological changes in periventricular white matter were observed by HE staining and immunohistochemistry.Results For the 3 groups,the structure in ope-ration side of the white matter in the peripheral ventricles of the brain 2 days postoperation were significant different （P 〈0.05）.The O4 positive cells decreased one by one/greatest in the SHAM group[（75.548 ± 7.333）/hpf] followed by MT group [（59.971 ± 3.635）/hpf],and HI group [（40.511 ± 2.848）/hpf] （P 〈 0.05）.The expression of Casepase-3 increased in the SHAM group （107.724 ± 10.266）,MT group （132.289 ± 8.537）,and HI group （202.168 ± 14.367）,and the difference was statically significant （P 〈 0.05）.Ventricular index was greater in operation side of the white matter in the peripheral ventricles of the 14-day-brain in the SHAM group（0.928 ±0.063）,MT group （1.813 ± 0.110）,HI group （2.752 ± 0.201）,increasingly,while absorbance value of myelin basic protein decreased one by one in sequence（39.504 ± 1.673,21.729 ± 1.614,11.344 ± 1.118）.Conclusions MT plays a role in protecting the periventricular white matter via inhibiting the apoptosis of oligodendrocyte progenitor cell,and thus benefits the PWMD.