摘要
目的:观察Aβ42沉积对大脑海马CD45、炎症因子和磷酸化tau蛋白(p-tau)表达的影响及白芍总苷(TGP)的干预作用。方法:应用立体定位注射技术对12周龄雌性SD大鼠1次性大脑海马定位注射纤丝状A 42复制AD病理模型,并给予白芍总苷进行干预,用免疫组化方法显示CD45、炎症因子及p-tau表达情况,并用分析软件进行图像分析。结果:与正常对照组相比,AD模型组的CD45、IL-1β、IL-6及p-tau阳性细胞染色面积(染色面积与染色的阳性细胞数成正比)均增加而染色强度值均下降(蛋白表达量与染色强度值成反比);与AD模型组比较,各给药组的IL-1β、IL-6染色面积均下降;除西乐葆对照组的IL-6染色强度值仅表现为增加的趋势外,其余各给药组的IL-1β、IL-6染色强度值均增加。另外,与AD模型组相比,白芍总苷高剂量组和西乐葆组的p-tau、CD45染色面积均下降而染色强度值均升高,TGP低剂量组的p-tau、CD45染色面积则有下降的趋势而染色强度值则有升高的趋势。结论:Aβ42沉积可诱导大脑海马炎症反应、小胶质细胞激活和炎症细胞因子过表达以及tau蛋白的过度磷酸化,而抑制小胶质细胞的激活及炎症细胞因子的过表达,从而抑制脑内炎症及tau蛋白的过度磷酸化,可能是TGP拮抗AD的主要作用机制。
Objective： To observe the effects of hippocampal Aβ42 deposition on the expression of inflammatory cytokines,CD45 and phospho-tau（p-tau）（Ser396） as well as the intervention of AD by total glucosides of paeony（TGP）.Methods： 12 week-old female SD rats were stereotactic injected one-time with a fibrillar Aβ42 positioning hippocampus to replicate AD pathology model and interfered with TGP.The expression of IL-1β,IL-6 and CD45 as well as p-tau were observed by immunohistochemistry（SABC）,and SABC images were analyzed by image analysis software.Results： Compared with the control group,the IL-1β,IL-6 and CD45,p-tau positive stained areas of AD pathology model group increased and their staining intensity decreased（the protein expression quantity inversely proportional to the staining intensity）;while the IL-1β,IL-6 and CD45,p-tau positive stained areas of the TGP groups and Celecoxib group decreased and their staining intensity increased compared with AD pathology model group.Conclusion： Aβ42 deposition in hippocampus can induce the microglial activation,hippocampal inflammation and the over-expression of IL-1β,IL-6 and CD45,p-tau.Inhibiting the over-expression of CD45,inflammatory cytokines and p-tau may be a major antagonistic mechanism of TGP for AD.
出处
《中药药理与临床》
CAS
CSCD
北大核心
2011年第4期36-39,共4页
Pharmacology and Clinics of Chinese Materia Medica
