Shenzhiling oral liquid (SZL) is a Traditional Chinese Medicine (TCM) compound to be approved by the China Food and Drug Administration (CFDA) (Z20120010) for the treatment of mild-to-moderate Alzheimer's disease (AD). However, its mechanism in early AD is not clear. We studied its mechanism in protecting myelin. Three-month-old APPswe/PS1dE9double transgenic mice were used as AD model and wild-type C57BL/6 mice were used as control. After 3-month intervention, the Morris water maze was used to detect behavioural changes. Myelin mTOR pathway (PI3K, p-PI3K, Akt, p-Akt, mTOR, p-mTOR), myelin basic protein (MBP) and postsynaptic density protein 95 (PSD95) were detected by immunohistochemistry and western blot and reverse transcriptase polymerase chain reaction (RT-PCR). After 3 months of SZL treatment, compared with the model group (M), SZL medium-dose (SM) and SZL low-dose groups (SL) exhibited increased staying and crossing results in Morris water maze (P < 0.05). Compared with M, PI3K-positive cells in SM and SL groups were increased (P < 0.01), p-PI3K expression increased in the Donepezil group (D), SZL high-dose group (SH) and SM (P < 0.05); number of Akt-positive cells and Akt expression in D, SM and SL were increased (P < 0.01, P < 0.05); number of p-Akt- and mTOR-positive cells and mTOR expression in all drug-treated groups were significantly increased (P < 0.01); p-Akt and p-mTOR expression increased in all drug-treated groups (P < 0.05, P < 0.01); MBP expression in D and SH increased (P < 0.05), while in SM and SL it increased more significantly (P < 0.01); and PSD95 expression in D, SM and SL was increased (P < 0.05). RT-PCR results showed that compared with M, PI3K mRNA and Akt mRNA expression in all drug-treated groups increased, but there was no statistical difference (P > 0.05), mTOR mRNA expression in all the drug-treated groups increased significantly (P < 0.01) and MBP mRNA and PSD95 mRNA expression in D and SH increased (P < 0.05). SZL oral liquid could play a role in myelin protection in early AD.

译文

参之灵口服液 (SZL) 是经中国食品药品监督管理局 (CFDA) (Z20120010) 批准用于治疗轻中度阿尔茨海默氏病 (AD) 的中药 (TCM) 化合物。然而,它在公元早期的机制并不清楚。我们研究了其保护髓磷脂的机制。3个月大的APPswe/ps1de9双转基因小鼠作为AD模型,野生型C57BL/6小鼠作为对照。干预3个月后,使用Morris水迷宫检测行为变化。免疫组织化学、western blot和逆转录酶聚合酶链反应 (rt-pcr) 检测髓鞘mTOR通路 (PI3K、p-PI3K、Akt、p-Akt、mTOR、p-mTOR) 、髓鞘碱性蛋白 (MBP) 和突触后密度蛋白95 (PSD95)。SZL治疗3个月后,与模型组 (M) 相比,SZL中剂量组 (SM) 和SZL低剂量组 (SL) 在Morris水迷宫中的停留和交叉结果增加 (p  <  0.05)。与M组相比,SM组和SL组PI3K-positive细胞增加 (p  <  0.01),多奈哌齐组 (D) 、SZL高剂量组 (SH) 和SM组 (p  <  0.05) p-PI3K表达增加; D组Akt阳性细胞数和Akt表达增加,SM和SL升高 (p  <  0.01,p  <  0.05); 所有药物治疗组p-Akt和mTOR阳性细胞数和mTOR表达均显着增加 (p  <  0.01); p-Akt和p-mTOR在所有药物治疗组中表达增加 (p  <  0.05,p  <  0.01); MBP在D和SH中的表达增加 (p  <  0.05),而在SM和SL中的表达增加更明显 (p  <  0.01); PSD95在D、SM和SL中的表达增加 (p  <  0.05)。Rt-pcr结果显示,与M相比,所有药物治疗组PI3K mRNA和Akt mRNA的表达均增加,但无统计学差异 (p  >  0.05)。所有药物处理组mTOR mRNA表达均显着增加 (p  <  0.01),D和SH MBP mRNA和PSD95 mRNA表达增加 (p  <  0.05)。SZL口服液可在AD早期发挥髓鞘保护作用。

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