白藜芦醇对酒精暴露致新生小鼠小脑发育损伤的保护作用

Resveratrol protects newborn mice against ethanol-mediated developmental impairment in cerebellum

目的探索白藜芦醇(resveratrol,RSV)对新生期小鼠酒精暴露后小脑发育损伤的保护作用。方法选取同窝的子鼠按随机数字表法分成3组:对照组、酒精组和RSV+酒精组。运用免疫组织化学方法检测浦肯野细胞标记物(calbindin D-28K,CB)、伯格曼胶质细胞标记物脑脂结合蛋白(brain lipid binding protein,BLBP)及其胶质纤维酸性蛋白(glial fibrillary acidic protein,GFAP)、小胶质细胞标记物(small glial cell marker,Iba-1)在小脑的分布与表达;采用Western blot测定小脑核转录因子(nuclear factor-κB,NF-κB)的表达水平,分析白藜芦醇对酒精暴露致新生小鼠小脑损伤的保护作用。结果与对照组比较,酒精组第8天新生小鼠小脑小胶质细胞数目增多,NF-κB表达水平增加(P<0.05),浦肯野细胞数量减少及树突长度降低,且伯格曼胶质细胞纤维密度减少(P<0.05);与酒精组比较,RSV+酒精组新生小鼠小脑内激活态小胶质细胞数量减少,NF-κB表达水平降低(P<0.05),浦肯野细胞数量和树突长度以及伯格曼胶质细胞纤维密度增加(P<0.05)。结论白藜芦醇能抑制酒精暴露导致的新生小鼠小脑小胶质细胞活化和NF-κB表达水平上调,促进浦肯野细胞和伯格曼胶质细胞的存活,改善酒精暴露导致的新生小鼠小脑发育损伤。

Objective To determine the protective effect of resveratrol neonatal mice exposed to ethanol （EtOI-I）. Methods Mice from the same （RSV） on the cerebellum of litters were randomized into control group, EtOH group and RSV ＋ EtOH group. Immunohistochemical assays were adopted to detect calbindin D-28K （CB） for Purkinje cells, brain lipid binding protein （BLBP） and glial fibrillary acidic protein （GFAP） for Bergmann glia, and small glial cell marker （Iba-1） for microglia, and meanwhile, the expression level of nuclear factor-K-gene binding protein （NF-KB） was assessed by Western blotting. Results Compared with the control group, after the neonatal mice （on the postnatal day 8, PD8 ） were exposed to EtOH, Purkinje cells and their dendritic length were decreased （ P 〈 0. 05 ）, the density of Bergmann glial fibers was lowered （ P 〈 0. 05 ）, but activated mieroglia and NF-KB level were increased （ P 〈 0.05）. In the RSV ＋ EtOH group, RSV could inhibit the over-activation of microglia and decrease the expression level of NF-KB in the cerebellum after EtOH exposure （ P 〈 0.05 ）. Purkinje cells and their dendritic length, and the density of Bergmann glial fibers were increased compared with the EtOH group （P 〈 0. 05）. Conclusion RSV can protect Bergmann glia and Purkinje cells from EtOH exposure through inhibiting over-expression of NF-KB and over-activation of microglia in the development of the neonatal cerebellum, and alleviate EtOH-mediated developmental impairment in the mouse cerebellum.