Liu Yong-Hui, Li Shao-Wei, Zheng Qing-Lian
Department of Traditional Chinese Medicine, The First Affiliated Hospital, Medical School of Xi'an Jiaotong University, Xi'an 710061.
Zhongguo Zhong Xi Yi Jie He Za Zhi. 2012 Apr;32(4):504-9.
To explore the effects of Bushen Jiannao Recipe (BJR) on the content of acetylcholine (Ach) and ERK1 and ERK2 protein expressions in the hippocampal CA1 region of vascular dementia (VD) rats, and to explore its possible mechanisms for treating VD.
Eighty-three rats were selected. The VD model was established by permanent bilateral occlusion of both common carotid arteries (2-VO). Then the modeled rats were randomly divided into 5 groups, i. e., the memory deficit model group, the donepezil group, and the positive drug control groups [including high (n = 13), middle (n = 13), and low (n = 12) dose BJR group]. Besides, another 13 rats were chosen as the sham-operative group. The distilled water was given by gastrogavage to rats in the sham-operative group and the memory deficit model group (5 mL/kg). The donepezil hydrochloride suspension was given to rats in the donepezil group by gastrogavage (0.52 mg/kg). High (56 g/kg), middle (28 g/kg), and low (14 g/kg) dose of BJR were respectively given to rats in the other three groups. After 30 days of intervention, the escape latency period and platform crossing times were determined using Morris water maze experiment. The contents of Ach in the hippocampus and cortex were determined using colorimetry. The expressions of ERK1 and ERK2 in the CA1 region of the hippocampus were detected using immunohistochemical assay.
The average escape latency of intervened rats showed an overall decreasing trend. From the third to the fifth day, the escape latency period was prolonged, the platform crossing times were reduced, the contents of Ach in the cortex and the hippocampus were lowered, the numbers of positive stained neuron of ERK1 and ERK2 in the hippocampus CA1 region were reduced, showing statistical difference when compared with the sham-operative group (P<0.01). Compared with the model group, the 4th day escape latency of the donepezil group and the high dose BJR group was shortened. The escape latency was shortened, and the platform crossing times, and the numbers of positive stained neuron of ERK1 and ERK2 in hippocampus CA1 region increased on the fifth day. The contents of Ach in the cortex and the hippocampus increased with statistical difference (P<0.05). Compared with the low dose BJR group, the 4th- and 5th-day latency period were shortened, the positive numbers of ERK1 and ERK2 in the hippocampus CA1 region increased in the high dose BJR group with statistical difference (P<0.05). Compared with the donepezil group, the Ach content in the cortex and the hippocampus of the middle and low dose BJR groups decreased (P<0.05).
BJR could obviously improve the function of learning and memory of VD rats. Its mechanisms might be associated with its actions in enhancing Ach contents of the cortex and the hippocampus, and promoting the protein expressions of ERK1 and ERK2 in the hippocampus CA1 region.
探讨补肾健脑方（BJR）对血管性痴呆（VD）大鼠海马CA1区乙酰胆碱（Ach）含量及ERK1和ERK2蛋白表达的影响，并探讨其治疗VD的可能机制。
选取83只大鼠。采用双侧颈总动脉永久性闭塞法（2-VO）建立VD模型。然后将造模成功的大鼠随机分为5组，即记忆缺陷模型组、多奈哌齐组和阳性药物对照组[包括高剂量（n = 13）、中剂量（n = 13）和低剂量（n = 12）BJR组]。另外选取13只大鼠作为假手术组。假手术组和记忆缺陷模型组大鼠给予蒸馏水灌胃（5 mL/kg）。多奈哌齐组大鼠给予盐酸多奈哌齐混悬液灌胃（0.52 mg/kg）。其他三组大鼠分别给予高剂量（56 g/kg）、中剂量（28 g/kg）和低剂量（14 g/kg）的BJR。干预30天后，采用Morris水迷宫实验测定逃避潜伏期和平台穿越次数。采用比色法测定海马和皮质中Ach的含量。采用免疫组织化学法检测海马CA1区ERK1和ERK2的表达。
干预后大鼠平均逃避潜伏期总体呈下降趋势。从第3天到第5天，逃避潜伏期延长，平台穿越次数减少，皮质和海马中Ach含量降低，海马CA1区ERK1和ERK2阳性染色神经元数量减少，与假手术组相比差异有统计学意义（P<0.01）。与模型组相比，多奈哌齐组和高剂量BJR组第4天逃避潜伏期缩短。第5天逃避潜伏期缩短，平台穿越次数以及海马CA1区ERK1和ERK2阳性染色神经元数量增加。皮质和海马中Ach含量增加，差异有统计学意义（P<0.05）。与低剂量BJR组相比，高剂量BJR组第4天和第5天潜伏期缩短，海马CA1区ERK1和ERK2阳性数量增加，差异有统计学意义（P<0.05）。与多奈哌齐组相比，中剂量和低剂量BJR组皮质和海马中Ach含量降低（P<0.05）。
BJR可明显改善VD大鼠的学习记忆功能。其机制可能与其提高皮质和海马中Ach含量以及促进海马CA1区ERK1和ERK2蛋白表达有关。
