摘要
目的:观察Aβ42沉积对大脑海马炎症因子和磷酸化MAPK信号分子表达的影响及白芍总苷(TGP)的干预作用。方法:选用12周龄雌性SD大鼠,随机分为6组,应用立体定位注射技术一次性大脑海马定位注射纤丝状Aβ42复制AD病理模型,并给予TGP(0.822,0.411 g.kg-1.d-1)进行干预,以西乐葆(0.183 g.kg-1.d-1)为对照,用免疫组化方法显示炎症因子及磷酸化MAPK通路信号分子表达情况,并用分析软件进行图像分析。结果:与对照组相比,AD模型组的IL-1β,IL-6及p-p38,p-JNK,p-MEK3/6的阳性细胞染色面积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模型组相比,各给药组的IL-1β,IL-6阳性染色面积均下降;TGP高、低剂量组的IL-1β,IL-6染色强度值均明显增加,西乐葆对照组的IL-1β染色强度值亦增加,而IL-6染色强度值仅表现为增加的趋势。另外,与AD模型组比较,除了TGP低剂量组的p-JNK表现为降低的趋势外,其余各给药组的p-p38,p-JNK,p-MEK阳性染色面积均明显下降;而除了TGP高剂量组的p-p38及西乐葆组的p-MEK3/6无明显变化外,其余各给药组的p-p38,p-JNK,p-MEK3/6染色强度值均明显增加。结论:Aβ42沉积可诱导大脑海马炎症反应和炎症细胞因子IL-1β,IL-6及磷酸化MAPK信号分子p-p38,p-JNK,p-MEK3/6等的过表达,而抑制IL-1β,IL-6及磷酸化MAPK信号分子的过表达,从而抑制AD模型脑内炎症,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 and phosphorylated MAPK signal molecules as well as the intervention of AD by total glucosides of paeony（TGP）.Method： 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 inflammatory cytokines and phosphorylated MAPK pathway signaling molecules were observed by immunohistochemistry（SABC）,and SABC images were analyzed by image analysis software.Result： Compared with the control group,the IL-1β,IL-6 and p-p38,p-JNK,p-MEK3/6 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 p-p38,p-JNK,p-MEK3/6 positive stained areas of the treatment groups decreased and their staining intensity increased compared with AD pathology model group.Conclusion： Aβ42 deposition in hippocampus can induce the brain inflammation and the over-expression of IL-1β,IL-6 and p-p38,p-JNK,p-MEK3/6.Inhibiting the over-expression of inflammatory cytokines and phosphorylated MAPK signaling molecules may be a major antagonistic mechanism of TGP against AD.
出处
《中国中药杂志》
CAS
CSCD
北大核心
2011年第6期795-800,共6页
China Journal of Chinese Materia Medica
关键词
白芍总苷
阿尔茨海默病
炎症因子
MAPK通路
total glucosides of paeony
Alzheimer
disease
inflammatory cytokines
MAPK pathway
