红花黄色素对APP/PS 1双转基因小鼠脑组织中胶质细胞活化及炎症因子释放的影响

Effects of safflower yellow on activation of glial cells and inflammation reaction in brain tissues of APP/PS1 transgenic mice

目的:探讨红花黄色素(SY)对阿尔茨海默病(Alzheimer's disease AD)转基因小鼠学习记忆能力的影响及其对脑组织中胶质细胞活化和炎症因子释放的影响。方法:选用6月龄APP/PS 1双转基因小鼠60只,随机分成5组:转基因组、多奈哌齐组(0.75 mg/kg)、红花黄色素10、30、100 mg/kg剂量组,同月龄野生型C57BL/6小鼠12只作为对照组,其中转基因组与对照组灌胃相应体积的生理盐水。连续3个月灌胃给予相应药物治疗后,进行Morris水迷宫实验。采用免疫组织化学法检测GFAP及CD45的表达,ELISA试剂盒测定各组小鼠皮层中IL-6、IL-8及TNF-α的表达。结果:与野生型小鼠相比,转基因组小鼠空间学习记忆能力明显下降,皮层及海马CA1、CA3、DG区的CD45、GFAP表达水平均增高,皮层组织中TNF-α、IL-6、IL-8水平显著增加。经红花黄色素治疗后,红花黄色素10、30、100 mg/kg剂量组学习记忆能力显著改善,其对GFAP、CD45、IL-6、IL-8及TNF-α的表达具有显著降低的作用;红花黄色素100 mg/kg剂量组对转基因小鼠海马各区CD45、皮层及海马部位GFAP以及皮层IL-6、IL-8的表达均有显著降低的作用;红花黄色素10 mg/kg剂量组对小鼠大脑海马CA1、CA3及皮层部位的CD45、海马及皮层部位的GFAP、皮层IL-8的表达有显著降低的作用。结论:红花黄色素可以提高痴呆小鼠的学习记忆能力,同时可抑制脑组织胶质细胞活化,减轻皮层组织炎症损伤。

Objective： To observe the influence of safflower yellow（SY） on learning and memory abilities of dementia mice and discuss its influence on activation of glial cells and inflammatory injury in brain tissues of APP/PS1 double transgenic mice modeling Alzheimer＇s disease（AD）.Methods： Six-month-old APP/PS1 transgenic mice were used in this study. The mice were randomly divided into five groups： transgenic group,donepezil group（0. 75 mg/kg）,10,30,100 mg/kg groups of Safflower Yellow,and wild-type mice with the same age were selected into the control group. All mice were performed Morris water maze test after given different drugs by gavage for three months. Expressions of CD45 and GFAP were measured in hippocampus and prefrontal cortex by immunohistochemistry,levels of IL-6,IL-8 and TNF-α in cortex were detected by ELISA. Results： Compared with wild-type group,the ability of learning and memory decreased in the transgenic group. Expressions of CD45 and GFAP in the hippocampal CA1,CA3,DG region and prefrontal cortex were increased. Levels of TNF-α,IL-6 and IL-8 in the cortex increased. After SY treatment,learning and memory abilities in 10,30,100 mg/kg groups were elevated,it obviously downregulated expressions of CD45,GFAP,IL-6,IL-8 and TNF-α,100 mg/kg down-regulated expressions of CD45 in the hippocampus and GFAP in the hippocampus and prefrontal cortex,it also decreased levels of IL-6 and IL-8 in the prefrontal cortex,10 mg/kg obviously downregulated the expression of CD45 in the hippocampal CA1,CA3 regions and prefrontal cortex,the content of GFAP in the hippocampal and cortex,the level of IL-8 in the cortex. Conclusion： Safflower Yellow could improve the ability of learning and memory and exert protective effects on activation of glial cells and inflammation damage in the cortex of APP/PS1 transgenic mice.