Sun Chengcheng, Liu Jiangang, Li Nannan, Liu Meixia, Luo Zenggang, Li Hao
Xiyuan Hospital, China Academy of Chinese Medical Sciences, Beijing 100091, China.
Beijing Administration of Traditional Chinese Medicine, Beijing 100053, China.
Evid Based Complement Alternat Med. 2021 Mar 30;2021:6648455. doi: 10.1155/2021/6648455. eCollection 2021.
This study aimed to illustrate the mechanism by which Shenmayizhi decoction (SMYZD) improves the learning memory of rats with vascular cognitive impairment (VCI). Fifty male and female Wistar rats of specific pathogen-free grade (SPF grade) were used to establish the model by the administration of a microsphere embolization. This was accomplished by injecting sterile, standardized, mass-produced microspheres of uniform particle size (100-200 m in diameter) in a sodium alginate microsphere vascular embolic agent suspension to induce VCI. The VCI model was successfully established in 40 rats, including both male and female rats, and the rats were randomly divided into 4 groups of 10 rats each. The model group was administered an equal volume of distilled water. The donepezil group was administered 0.45 mg/kg/d donepezil, which is equivalent to the clinical dosage. The SMYZ-H group was administered 11.88 g/kg/d SMYZ, which is 4 times higher than the clinically equivalent dosage. The SMYZ-L group was administered 2.97 g/kg/d SMYZ, which is the clinically equivalent dosage. A sham-operated group was used as the control group and administered an equal volume of distilled water. The rats in the 4 groups were treated by gavage with equal volumes of liquid and the indicated concentration of drug diluted in distilled water for 8 consecutive weeks. Two months later, the Morris water maze (MWM) was used to evaluate the spatial memory of all the rats. Ultrastructural and ultrapathological changes in the capillaries of the cerebral cortex were observed by transmission electron microscopy. Furthermore, Western blot and RT-PCR analyses were used to assess the levels of platelet-derived growth factor receptor- (PDGFR-), neuron-glial antigen 2 (NG2), vascular endothelial growth factor A (VEGF-A), and angiopoietin 1 (Ang1) in the cerebral cortex of the rats. The results showed that SMYZD at concentrations of 11.88 g/kg/d and 2.97 g/kg/d (SMYZ-H and SMYZ-L) significantly shortened the escape latency (EL). In addition, SMYZ-H significantly prolonged the distance traveled and the time spent in the original platform quadrant by the rats with VCI. SMYZ-H significantly increased the NG2 and Ang1 protein expression levels and increased the PDGFR- and Ang1 mRNA levels. These results demonstrated that Shenmayizhi decoction can improve the memory abilities of rats with VCI induced by multiple cerebral infarctions by preventing pericyte degeneration.
本研究旨在阐明参麦益智汤（SMYZD）改善血管性认知障碍（VCI）大鼠学习记忆的机制。采用50只无特定病原体等级（SPF级）的Wistar大鼠，通过微球栓塞法建立模型。具体做法是将无菌、标准化、批量生产的粒径均匀（直径100 - 200μm）的微球注入海藻酸钠微球血管栓塞剂混悬液中以诱导VCI。在40只大鼠（包括雄性和雌性）中成功建立了VCI模型，将这些大鼠随机分为4组，每组10只。模型组给予等体积蒸馏水。多奈哌齐组给予0.45mg/kg/d多奈哌齐，相当于临床剂量。参麦益智高剂量组（SMYZ-H）给予11.88g/kg/d参麦益智汤，为临床等效剂量的4倍。参麦益智低剂量组（SMYZ-L）给予2.97g/kg/d参麦益智汤，即临床等效剂量。假手术组作为对照组，给予等体积蒸馏水。4组大鼠连续8周每天经口灌胃给予等体积液体及用蒸馏水稀释至指定浓度的药物。两个月后，采用Morris水迷宫（MWM）评估所有大鼠的空间记忆。通过透射电子显微镜观察大脑皮质毛细血管的超微结构和超微病理变化。此外，采用蛋白质免疫印迹法（Western blot）和逆转录-聚合酶链反应（RT-PCR）分析评估大鼠大脑皮质中血小板衍生生长因子受体-β（PDGFR-β）、神经元胶质抗原2（NG2）、血管内皮生长因子A（VEGF-A）和血管生成素1（Ang1）的水平。结果显示，浓度为11.88g/kg/d和2.97g/kg/d的参麦益智汤（SMYZ-H和SMYZ-L）显著缩短了逃避潜伏期（EL）。此外，SMYZ-H显著延长了VCI大鼠在原平台象限的游动距离和停留时间。SMYZ-H显著提高了NG2和Ang1蛋白表达水平，并提高了PDGFR-β和Ang1 mRNA水平。这些结果表明，参麦益智汤可通过防止周细胞变性来改善多发性脑梗死诱导的VCI大鼠的记忆能力。
