DNA疫苗对APP/PS1转基因鼠免疫反应类型及脑内炎症反应的影响

Effect of DNA vaccine on immune response and inflammation in the brain of APP/PS1 transgenic mice

目的探讨DNA疫苗p(Aβ3-10)10-mIL-4免疫阿尔茨海默病转基因鼠(APP/PS1)免疫反应类型及对脑内炎症反应的影响。方法构建DNA疫苗p(Aβ3-10)10-mIL-4,用其免疫APP/PS1转基因鼠,Aβ42肽及pcDNA3.1(+)作为对照组。ELISA法检测免疫后转基因鼠脾细胞培养上清中白细胞介素-4(IL-4)及γ干扰素(IFN-γ)的含量,免疫荧光检测小鼠脑内老年斑及小胶质细胞。结果 Aβ42组及p(Aβ3-10)10-mIL-4组的IL-4的含量均明显高于pcDNA3.1(+)组(P<0.01),但是两组比较无显著差异(P>0.05)。Aβ42组的IFN-γ的含量明显高于p(Aβ3-10)10-mIL-4组及pcDNA3.1(+)组(P<0.01),而p(Aβ3-10)10-mIL-4组和pcDNA3.1(+)组比较没有显著差别(P>0.05,)。Aβ42组及p(Aβ3-10)10-mIL-4组脑组织中老年斑及小胶质细胞与pcDNA3.1(+)组相比明显减少。结论DNA疫苗p(Aβ3-10)10-mIL-4免疫APP/PS1转基因鼠后,产生了Th2型免疫反应,减轻小鼠脑内Aβ沉积,同时可以改善鼠脑内的炎症反应,可以作为阿尔茨海默病的候选疫苗进一步进行研究。

Objective To study the immune response and inflammation in the brain of Alzheimer’s disease transgenic mice(APP/PS1)which were immunized by DNA vaccinep(Aβ3-10)10-mIL-4.Methods DNA vaccine p(Aβ3-10)10-mIL-4was constructed.APP/PS1 transgenic mice were vaccinated with p(Aβ3-10)10-mIL-4.Aβ42peptide and pcDNA3.1(+)were chosen to the control groups.IL-4and IFN-γin splenocyte culture supernatants from immunized transgenic mice were detected after vaccination by enzyme-linked immunosorbent assay(ELISA).The senile plaques and microglial in mouse brains were detected by immunofluorescence.Results Compare with pcDNA3.1(+)group,IL-4levels of p(Aβ3-10)10-mIL-4group and Aβ42peptide group were significantly higher(P<0.01),but there was no difference between them(P>0.05).IFN-γlevels of Aβ42peptide group were significantly higher than those of p(Aβ3-10)10-mIL-4group and pcDNA3.1(+)group(P<0.01),but there were no difference between p(Aβ3-10)10-mIL-4group and pcDNA3.1(+)group(P>0.05).Compare with pcDNA3.1(+)group,p(Aβ3-10)10-mIL-4and Aβ42peptide immunization decreased Aβdeposition and the microglial cells.Conclusion The immunization with p(Aβ3-10)10-mIL-4in APP/PS1 mice induced a Th2anti-inflammatory response,decreased Aβdeposition and reduced inflammation of the mice brain.And p(Aβ3-10)10-mIL-4can be an alternative Alzheimer’s disease vaccine to further study.