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目的研究中药I号方对APP/PS1双转基因模型小鼠APP代谢的影响。方法将5月龄APP/PS1双转基因模型小鼠随机分为模型组(vehicle)、中药Ⅰ号方低剂量组(0.6 g/kg)、中剂量组(1.2 g/kg)和高剂量组(2.4 g/kg),并以同窝阴性小鼠作为正常对照组(wild-type,WT),每组16只,雌雄各半。给药小鼠每天灌胃一次,模型组和正常对照组分别给予等体积的双蒸水灌胃。给药四个月后,用免疫组化和Western blot检测淀粉样前体蛋白(APP)及其代谢产物和分解酶的变化。结果 Western blot结果显示,与模型组相比,治疗组低剂量、中剂量和高剂量给药组能显著降低APP分解酶(ADAM10和BACE1)(P<0.01)及APP的分解产物的量,如:β-CTF(C99)、α-CTF(C83)、s APPα、s APPβ(P<0.01)。结论中药I号方通过影响APP的分解过程减少淀粉样蛋白(β-amyloid peptide,Aβ)的生成,减少脑内老年斑的沉积。
Objective To study the effect of Chinese medicine I on APP metabolism in APP / PS1 double transgenic mice. METHODS: Five-month-old APP / PS1 double transgenic mice were randomly divided into four groups: model group, low dose group Ⅰ 0.6 g / kg, middle dose group 1.2 g / kg and high dose group 2.4 g / kg). The same litter-negative mice were used as normal control group (WT) with 16 mice in each group. Administration of mice once daily gavage, the model group and normal control group were given equal volume of double distilled water gavage. Four months after administration, the changes of amyloid precursor protein (APP) and its metabolites and catabolic enzymes were examined by immunohistochemistry and Western blotting. Results Western blot results showed that the low, middle and high dosage groups of ADAM10 and BACE1 (P <0.01) and the amount of APP decomposition product of the treatment group were significantly lower than those of the model group : β-CTF (C99), α-CTF (C83), s APPα, s APPβ (P <0.01). Conclusion Chinese medicine I can reduce the formation of amyloid peptide (Aβ) and decrease the deposition of senile plaques in brain by affecting the process of APP decomposition.