| 摘要: |
| 目的 基于PI3K/Akt/哺乳动物雷帕霉素靶蛋白（mTOR）信号通路，研究党参远志散微乳对D-半乳糖联合亚硝酸钠所致皮质性痴呆小鼠模型海马神经元凋亡的影响及作用机制。方法 将60只ICR小鼠随机分为6组：空白组、模型组、生物相容性微乳组、吡拉西坦组、党参远志散微乳低剂量组和党参远志散微乳高剂量组，每组10只。除空白组外，其余5组均腹腔注射D-半乳糖（120 mg/kg）和亚硝酸钠（54 mg/kg）制备皮质性痴呆小鼠模型，并分别灌胃蒸馏水、生物相容性微乳（10 mL/kg）、吡拉西坦（0.63 g/kg）、低剂量党参远志散微乳（相当于生药材8.58 g/kg）和高剂量党参远志散微乳（相当于生药材17.16 g/kg），每天1次，连续6周。通过Morris水迷宫实验考察小鼠学习记忆能力，H-E染色观察海马皮质病理形态学改变，尼氏染色观察海马皮质神经元尼氏体变化，免疫组织化学染色观察海马皮质PI3K、Akt、mTOR表达情况，免疫荧光染色观察海马皮质双皮质素（DCX）表达和新生神经元生长情况。结果 与模型组比较，党参远志散微乳低、高剂量组皮质性痴呆小鼠学习记忆能力均改善，海马皮质病理形态改善，神经元胞体圆整、密集，神经元尼氏体含量丰富，海马皮质PI3K、Akt、mTOR蛋白表达降低，DCX蛋白表达增高，新生神经元增加、分布密集、胞体伸出突触增多。结论 党参远志散微乳低、高剂量可通过抑制PI3K/Akt/mTOR信号通路诱导自噬，减轻神经元损伤，诱导神经元新生，改善D-半乳糖和亚硝酸钠所致的皮质性痴呆模型小鼠的学习记忆能力。权衡效毒，党参远志散微乳应选用低剂量，即临床等效剂量。 |
| 关键词: 党参远志散微乳 皮质性痴呆 磷脂酰肌醇3-激酶 蛋白激酶B 哺乳动物雷帕霉素靶蛋白 |
| DOI：10.16781/j.CN31-2187/R.20210345 |
| 投稿时间：2021-04-01修订日期：2021-09-02 |
| 基金项目:山西省应用基础研究计划项目（201901D211539），山西省中医药管理局科研项目（2019ZYYC022）. |
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| Effect of Dangshen Yuanzhi powder microemulsion regulating PI3K/Akt/mTOR pathway on neuronal apoptosis in mice with cortical dementia |
| YANG Li-xia*,WANG Jing-rui,FENG Ting-ting,MA Chuan,AN Xiao-ting |
(Department of Basic Science, Institute of Pharmaceutical and Food Engineering, Shanxi University of Chinese Medicine, Jinzhong 030619, Shanxi, China
*Corresponding author) |
| Abstract: |
| Objective To study the effects of Dangshen Yuanzhi powder microemulsion on apoptosis of hippocampal neurons in mice with cortical dementia induced by D-galactose and sodium nitrite based on the phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt)/mammalian target of rapamycin (mTOR) signal pathway. Methods Sixty ICR mice were randomly divided into 6 groups:normal group, model group, biocompatible microemulsion group, piracetam group, low-dose group of Dangshen Yuanzhi powder microemulsion, and high-dose group of Dangshen Yuanzhi powder microemulsion, with 10 mice in each group. Except for the normal group, the other 5 groups were intraperitoneally injected with D-galactose (120 mg/kg) and sodium nitrite (54 mg/kg) to establish mouse models of cortical dementia. Distilled water, biocompatible microemulsion (10 mL/kg), piracetam (0.63 g/kg), low- and high-doses of Dangshen Yuanzhi powder microemulsion (equivalent to 8.58 g/kg and 17.16 g/kg of raw medicine) were given by gavage, once a day for 6 weeks. Memory ability was examined by Morris water maze test, pathomorphological changes were observed by hematoxylin-eosin staining, the changes of Nissl bodies of neurons in the hippocampal cortex were observed by Nissl staining, the expression of PI3K, Akt and mTOR in the hippocampal cortex was observed by immunohistochemistry, and the expression of doublecortin (DCX) and the growth of newborn neurons in hippocampal cortex were observed by immunofluorescence. Results Compared with the model group, the learning and memory ability of mice with cortical dementia was significantly improved in the low- and high-dose groups of Dangshen Yuanzhi powder microemulsion, the pathological morphology of the hippocampal cortex was obviously improved, the neurons were round and dense, the contents of Nissl bodies of neurons were abundant, the expression of PI3K, Akt and mTOR was significantly decreased, the expression of DCX was significantly increased, the distribution of newborn neurons was dense, and extended synapse was increased. Conclusion Low- and high-doses of Dangshen Yuanzhi powder microemulsion can induce autophagy by inhibiting PI3K/Akt/mTOR signaling pathway, reduce neuronal damage, induce neuronal regeneration, and improve learning and memory ability in mice with cortical dementia induced by D-galactose and sodium nitrite. Considering efficacy and toxicity, low-dose (the clinical equivalent dose) of Dangshen Yuanzhi powder microemulsion should be selected. |
| Key words: Dangshen Yuanzhi powder microemulsion cortical dementia phosphatidylinositol 3-kinase protein kinase B mammalian target of rapamycin |
