白藜芦醇对阿尔茨海默病模型大鼠海马组织星形胶质细胞及TNF-α表达的影响

Effects of resveratrol on hippocampal astrocytes and expression of TNF-α in Alzheimer's disease model rats

目的观察不同浓度白藜芦醇(Res)对阿尔茨海默病(AD)大鼠海马组织星形胶质细胞及TNF-α表达的影响。方法将60只Wistar雌性大鼠分为6组:假手术组,模型组,Res 20、40、80 mg/kg及戊酸雌二醇组(0.8 mg/kg),利用去卵巢合并D-半乳糖(100 mg/kg)腹腔注射建立AD模型,干预12周后,采用在体心脏灌流,固定海马组织,通过免疫组织化学法检测海马星形胶质细胞及肿瘤坏死因子α(TNF-α)表达的变化。结果模型组胶质纤维酸性蛋白(GFAP)及TNF-α表达量均明显高于假手术组(P<0.01)。Res 20 mg/kg组GFAP表达量与模型组比较,差异无统计学意义;Res 40、80 mg/kg及戊酸雌二醇组GFAP表达量明显低于模型组(P<0.01),而且随着Res浓度的增高,GFAP的表达量逐渐下降。Res 20、40、80 mg/kg,戊酸雌二醇组TNF-α表达量明显低于模型组(P<0.01)。结论 Res可通过抑制星形胶质细胞增殖活化以及TNF-α的分泌,进而改善AD大鼠的脑内炎症反应。

Objective To explore the effects of resveratrol on astrocyte and TNF-α in hippocampus of Alzheimer ＇s disease（ AD） model rats. Methods Sixty rats were randomly divided into six groups： sham control group,model group,resveratrol 20,40,80 mg / kg group,and estradiol valerate group（ 0. 8 mg / kg）. The model of AD was established by ovariectomy combined injection of D-galactose（ 100 mg / kg）. Twelve weeks later,the heart perfusion in vivo was done and then the hippocampus was fixed.Additionally,the changes of hippocampal astrocytes and TNF-α expression were detected by immunohistochemistry. Results The levels of glial fibrillary acidic protein（ GFAP）and TNF-α in the model group were significantly higher than those of the sham control group（ P〈0. 01）. No marked difference in the production of GFAP was observed between the resveratrol 20 mg / kg group and the model group（ P〉0. 05）. However,the resveratrol 40,80 mg / kg and estradiol valerate treated groups showed a decrease in the expression of GFAP compared with the model group（ P〈0. 01）. Moreover,with the increasing of resveratrol concentration,the expression of GFAP decreased gradually. Thelevels of TNF-α decreased markedly in Res 20,40,80 mg / kg and estradiol valerate group compared with the model group（ P〈0. 01）. Conclusion These results suggest that the activation of astrocytes and the secretion of TNF-α can be inhibited by Res in AD rats.