The Second Hospital Affiliated to Tianjin University of Traditional Chinese Medicine, Tianjin, 300150, China.
International Zhuang Medical Hospital, Nanning, Guangxi, 530201, China.
CNS Neurol Disord Drug Targets. 2020;19(4):276-289. doi: 10.2174/1871527319666200604174223.
Studies have found that autophagy could promote the clearance of Aβ. To promote and maintain the occurrence of autophagy in Alzheimer's Disease (AD) might be a potential way to reduce neuronal loss and improve the learning and memory of AD.
To investigate the possible mechanisms of Yishen Huazhuo Decoction (YHD) against AD model.
Forty 7-month-old male SAMP8 mice were randomly divided into model (P8) group and YHD group, 20 in each group, with 20 SAMR1 mice as control (R1) group. All mice were intragastrically administered for 4 weeks, YHD at the dosage of 6.24g/kg for YHD group, and distilled water for P8 group and R1 group. Morris Water Maze (MWM) test, Nissl's staining, TEM, TUNEL staining, immunofluorescence double staining, and western blot analysis were applied to learning and memory, structure and ultrastructure of neurons, autophagosome, apoptosis index, Aβ, LAMP1, and autophagy related proteins.
The escape latency time of YHD group was significantly shorter on the 4th and 5th day during MWM test than those in P8 group (P=0.011, 0.008<0.05), and the number of crossing platform in YHD group increased significantly (P=0.02<0.05). Nissl's staining showed that the number of neurons in YHD group increased significantly (P<0.0001). TEM showed in YHD group that the nucleus of neurons was slightly irregular, with slightly reduced organelles, partially fused and blurred cristae and membrane of mitochondria. The apoptosis index of YHD group showed a decreasing trend, without statistically significant difference (P=0.093>0.05), while Caspase3 expression in YHD group was significantly lower (P=0.044<0.05). YHD could promote the clearance of Aβ1-42 protein, improve the expression of Beclin-1 and p-Bcl2 proteins, reduce mTOR and p62 proteins.
YHD could induce autophagy initiation, increase the formation of autophagosomes and autolysosome, promote the degradation of autophagy substrates, thereby regulating autophagy, and promoting the clearance of Aβ1-42 to improve memory impairment in SAMP8 mice.
研究发现自噬可以促进 Aβ 的清除。在阿尔茨海默病（AD）中促进和维持自噬的发生可能是减少神经元丢失和改善 AD 学习记忆的潜在途径。
探讨益肾化浊方（YHD）防治 AD 模型的可能机制。
40 只 7 月龄雄性 SAMP8 小鼠随机分为模型（P8）组和 YHD 组，每组 20 只，以 20 只 SAMR1 小鼠为对照（R1）组。所有小鼠连续灌胃 4 周，YHD 组给予 YHD 剂量 6.24g/kg，P8 组和 R1 组给予蒸馏水。采用 Morris 水迷宫（MWM）试验、尼氏染色、透射电镜（TEM）、TUNEL 染色、免疫荧光双染、Western blot 分析检测学习记忆、神经元结构和超微结构、自噬体、凋亡指数、Aβ、LAMP1 和自噬相关蛋白。
MWM 试验中，YHD 组第 4、5 天逃避潜伏期明显短于 P8 组（P=0.011，0.008<0.05），穿越平台次数明显增多（P=0.02<0.05）。尼氏染色显示 YHD 组神经元数量明显增多（P<0.0001）。TEM 显示 YHD 组神经元核稍不规则，细胞器减少，线粒体嵴和膜部分融合、模糊。YHD 组凋亡指数呈下降趋势，但无统计学差异（P=0.093>0.05），Caspase3 表达明显降低（P=0.044<0.05）。YHD 能促进 Aβ1-42 蛋白的清除，提高 Beclin-1 和 p-Bcl2 蛋白的表达，降低 mTOR 和 p62 蛋白。
YHD 可诱导自噬启动，增加自噬小体和自噬溶酶体的形成，促进自噬底物的降解，从而调节自噬，促进 Aβ1-42 的清除，改善 SAMP8 小鼠的记忆障碍。
