摘要
目的:观察Aβ42沉积对大脑海马炎症因子和磷酸化丝裂原活化蛋白激酶(mitogen activated protein kinase,MAPK)信号分子表达的影响及加味当归芍药散(JWDSS)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对SD大鼠1次性大脑海马定位注射纤丝状Aβ42复制AD病理模型,并给予JWDSS(剂量分别为70.654,35.327 g.kg-1.d-1)进行干预,以西乐葆(剂量0.183 g.kg-1.d-1)为对照,用免疫组化(SABC)方法显示炎症因子及磷酸化MAPK信号分子表达情况,并用分析软件进行图像分析。结果:与正常对照组相比,AD模型组的白细胞介素-1β(interleukin-1β,IL-1β),IL-6,phospho-p38(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);各给药组的IL-1β,IL-6阳性细胞染色面积较AD模型组下降;JWDSS高、低剂量组的IL-6及JWDSS高剂量组的IL-1β染色强度值均较AD模型组增加,而JWDSS低剂量组的IL-1β染色强度值亦呈增加的趋势;西乐葆对照组的IL-1β染色强度值亦较AD模型组增加,而IL-6染色强度值呈增加的趋势。另外,除了JWDSS低剂量组的p-JNK外,其余各给药组的p-p38,p-JNK,p-MEK3/6阳性细胞染色面积与AD模型组相比均明显下降,而染色强度值均较AD模型组明显增加。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p-p38,p-JNK,p-MEK3/6的过表达,而抑制炎症因子及磷酸化MAPK信号分子的过表达,从而抑制AD模型脑内炎症,可能是JWDSS拮抗AD的主要作用机制。
Objective： To observe the effects of Aβ42 deposition on the expression of hippocampal inflammatory cytokines and phosphorylated mitogen-activated protein kinase（MAPK） signal molecules,and the intervention by Modified Danggui Shaoyao Powder（JWDSS）.Method： Alzheimer＇s disease（AD） model was established by stereotactic injection of fibrillar Aβ42 into the hippocampus of 12 week-old female SD rats being divided into 6 groups.JWDSS（70.654,35.327 g·kg-1·d-1） was given for intervention,and celebrex（0.183 g·kg-1·d-1） was used as control.Expression of inflammatory cytokines and phosphorylated MAPK pathway signaling molecules were observed by immunohistochemistry（SABC） methods and SABC images were analyzed by an image analyzing software.Result： Compared with the control group,the positive stained areas of interleukin-1β（IL-1β）,IL-6 and phospho-p38（p-p38）,p-JNK and p-MEK3 /6 increased with decreased staining intensity in the modelgroup.Protein expression quantity was inversely proportional to the staining intensity.The positive stained areas of IL-1β,IL-6 and p-p38,p-JNK and p-MEK3 /6 in the treatment groups decreased and their staining intensity increased,compared with the AD model group.Conclusion：Aβ42 deposition in hippocampus can induce inflammation of the brain and 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 JWDSS for AD.
出处
《中国实验方剂学杂志》
CAS
北大核心
2011年第2期143-148,共6页
Chinese Journal of Experimental Traditional Medical Formulae
关键词
加味当归芍药散
阿尔茨海默病
炎症因子
MAPK通路
大鼠
Modified Danggui Shaoyao Powder
Alzheimer＇s disease
inflammatory cytokines
MAPK pathway
rat
