淫羊藿次苷Ⅱ下调APP/PS1转基因小鼠海马APP、Aβ_(1-42)、RAGE蛋白水平并抑制炎症反应

Icariside II down-regulates protein level of APP,Aβ_(1-42),RAGE and suppresses inflammatory response in APP/PS1 transgenic mice

目的探索淫羊藿次苷Ⅱ(ICS Ⅱ)对APP/PS1转基因小鼠海马APP、Aβ_(1-42)、RAGE蛋白水平及炎症反应的影响。方法野生型小鼠和APP/PS1转基因小鼠分为5个组:野生型对照组、野生型高剂量组、APP/PS1转基因组、APP/PS1转基因低剂量组和APP/PS1转基因高剂量组,每组15只。野生型小鼠为同月龄同背景C57BL/6J小鼠。低、高剂量组每日1次分别灌胃ICS Ⅱ 10、20 mg/kg,野生型对照组和APP/PS1转基因组灌胃等体积生理盐水,连续7个月。随后取材,Western blot法检测小鼠海马组织淀粉样前体蛋白(APP)和β淀粉样肽1-42(Aβ_(1-42))蛋白水平,晚期糖基化终产物受体(RAGE)的蛋白表达,促炎细胞因子[肿瘤坏死因子-α(TNF-α)和环氧合酶-2(COX-2)]蛋白表达,抗炎因子白细胞介素-10(IL-10)蛋白表达。结果 ICS Ⅱ可显著降低APP/PS1转基因小鼠海马组织APP、Aβ_(1-42)、RAGE蛋白水平,降低炎症因子COX-2、TNF-α蛋白水平,增加抗炎因子IL-10蛋白水平(P<0.05)。野生型小鼠给予ICS Ⅱ后,上述指标无显著变化。结论 ICS Ⅱ可下调APP/PS1转基因小鼠海马RAGE、APP、Aβ_(1-42)蛋白水平和减轻炎症反应。

Objective To explore the effects of icariside Ⅱ（ ICS Ⅱ） on the protein levels of amyloid precursor protein（ APP）,Aβ1-42 and RAGE,and inflammatory response in APP/PS1 transgenic mice. Methods C57BL/6J wild-type（ WT） mice and APP/PS1 transgenic mice were divided into 5 groups（ n = 15 in each group） ：WT ＋ NS（ volume-matched normal saline）,WT ＋ ICS Ⅱ 20（ 20 mg/kg）,APP/PS1 ＋ NS（ volume-matched normal saline）,APP/PS1 ＋ ICS Ⅱ 10（ 10 mg/kg）,APP/PS1 ＋ ICS Ⅱ 20（ 20 mg/kg）. The mice received intragastric administrated once a day for 7 months. After the sacrifice of mice,Western blot assay was used to detect the protein levels of amyloid precursor protein（ APP）,β amyloid protein1-42（ Aβ1-42）,receptor for advanced glycation end products（ RAGE）,tumor necrosis factor（ TNF-α）,interleukin-10（ IL-10）,and cyclooxygenase-2（ COX-2）. Results The protein levels of APP,Aβ1-42,COX-2,TNF-α,RAGE were increased in APP/PS1 group compared with those in the WT group（ P 〈 0. 05）. Moreover,the protein level of IL-10 was decreased in APP/PS1 group compared with that in the WT group（ P 〈 0. 05）. The treatment with ICS Ⅱ（ 20 mg/kg） significantly decreased the protein levels of APP,Aβ1-42,COX-2,TNF-α,RAGE in APP/PS1 group compared with those in APP/PS1 group（ P 〈 0. 05）. And IL-10 protein level was increased compared with that in APP/PS1 group（ P 〈 0. 05）. Conclusion ICS Ⅱ down-regulates the protein levels of RAGE,APP,Aβ1-42,and suppresses inflammatory response in APP/PS1 transgenic mice.