黄连解毒汤对APP/PS1双转基因AD小鼠海马区病理形态学及脑内β-APP基因mRNA的影响

Effects of Huanglian Jiedu Decoction on β-Amyloid Precuser Protein mRNA and on the Pathological Changes in Hippocampus of APP/PS1 Transgenic Mouse Model

目的:探讨黄连解毒汤(HLJDD)对APP/PS1双转基因阿尔茨海默病(AD)模型小鼠海马CA1区的病理形态学及脑内β-淀粉样前体蛋白(β-APP)基因mRNA的影响。方法:选用3月龄的APP/PS1双转基因AD小鼠模型50只,随机分为对照组、安理申组、HLJDD大剂量组、HLJDD中剂量组、HLJDD小剂量组各10只,分别给予安理申或不同剂量HLJDD灌胃治疗6个月,对照组不予治疗,记录并比较各组死亡率;分别于6月龄和10月龄时采用HE染色观察各组海马CA1区神经细胞形态,采用改良甲醇刚果红染色观察各组老年斑形成情况;于末次灌胃治疗后,通过实时荧光定量PCR检测各组脑内β-APPmRNA水平。结果:各组小鼠死亡率差异无统计学意义;10月龄HLJDD各剂量组海马CA1区神经损伤情况较对照组明显减轻,老年斑数量少于对照组(P<0.05);HLJDD各剂量组β-APPmRNA水平低于对照组(P<0.05),其中以中剂量组水平降低最明显(P<0.01)。结论:HLJDD能保护海马神经细胞。

Objective： To explore the effects of huanglian jiedu decoction（HLJDD） on the transcription of β-Amyloid Precuser Protein （β-APP） mRNA and the pathological changes in the hippocampus of APP/PS1 transgenic mouse model of Alzheimer＇s disease （AD）. Methods： Fifty 3-month-old APP/PS1 transgenic AD mice were randomly divided into control group （n = 10）, Ayicept group （n=10）, HLJDD high dose group （n=10）, HLJDD medium dose group （n=10） and HLJDD low dose group （n= 10）. Mice were treated with Aricept or HLJDD in different doses and the mice in the control group received no treatments. The mortality rates in different groups were calculated. HE staining and Congo red staining were performed to observe the mor- phology of hippocampal neuronal cells and the senile plaques（SP）respectively. The transcription of β-APP mRNA was detected by real-time quantitative PCR. Results： There was no differences in mortality rate in the different groups. When compared with that in the control group, the neu- rologic damage in the hippocampus, the number of SP and the transcription of β-APP mRNA were significantly decreased in mice in all the HLJDD groups, especially in the HLJDD medium dose group. Conclusion： HLJDD is a safe and effective therapeutic way to protect the hippocam pal neuronal cells.