早期营养不良上调成年期SD大鼠海马小胶质细胞活化水平

Effect of early malnutrition on up-regulation of activation of microglia in adult SD rat hippocampal

目的:研究早期营养不良对成年期SD大鼠海马小胶质细胞活化水平的影响。方法:建立早期营养不良SD大鼠模型,建模结束后给予n-3多不饱和脂肪酸(n-3-polyunsaturated fatty acid,n3-PUFA)干预。检测仔鼠体质量,Morris水迷宫实验和场景恐惧实验检测学习记忆能力,RT-q PCR和Western blot检测海马小胶质细胞M1型标志物诱导型一氧化氮合酶(inducible nitric oxide synthase,i NOS)、环氧合酶-2(cyclooxygenase-2,COX-2)m RNA和蛋白的表达,免疫组化检测海马小胶质细胞标志物离子钙结合配适分子-1(ionized calcium-binding adapter molecule-1,IBA-1)的表达。结果:早期营养不良组仔鼠出生后体质量偏低(P=0.000),成年期学习记忆能力下降,i NOS m RNA表达增加(P=0.002),i NOS蛋白表达增加(P=0.015),IBA-1表达增加(P=0.047)。给予n3-PUFA补充后可以减少小胶质细胞M1型转化,降低活化水平。结论:早期营养不良可以上调仔鼠成年期海马小胶质细胞活化水平,诱导M1型转化,可能与神经炎症的发生相关。

Objective：To investigate the effect of early malnutrition on the activation of microglia in the hippocampus of adult rats.Methods：Early malnutrition model was established in SD rat,and all rats were given supplement of n-3-polyunsaturated fatty acid（n3-PUFA）after lactation. Weight of newborn rats was measured. The ability of learning and memory of offspring rats were assayed by Morris water maze and the fear conditioning. Real-time quantitative PCR and Western blot were used to assay the expression of microglia M1 markers such as inducible nitric oxide synthase（i NOS）,cyclooxygenase-2（COX-2）in the hippocampus. The expressions of microglia marker Ionized calcium binding adapter molecule-1（IBA-1）in the hippocampus were detected by immunohistochemistry. Results：The early malnutrition group was born with lower birth weight（P=0.000）. After postnatal 90 days,the ability of learning and memory was reduced;the expression of i NOS was increased both in m RNA（P =0.002） and protein（P =0.015）;the expression of IBA-1 was increased（P=0.047）. Supplementation of n3-PUFA could reduce M1 type conversion and the activation of microglia. Conclusion：Early malnutrition may lead to up-regulation of activation of microglia and increasing of M1 phenotypic transformation in adult offspring,which may be related to the occurrence of neuroinflammation in hippocampus of adulthood.