Objective: To observe the therapeutic effect of Yangxue Qingnao Granule YXQNG) on cognitive impairment induced by chronic cerebral hypoperfusion and to investigate its impact on oxidative stress, apoptosis, and the cholinergic system. Methods: Adult male Wistar rats were subjected to chronic cerebral hypoperfusion by permanent occlusion of bilateral common carotid arteries (2-VO). Thirty rats were randomly assigned to one of the five treatment groups in a 1:1:1:1:1 ratio: sham operation plus normal saline treatment, 2-VO plus normal saline treatment, 2-VO plus YXQNG at a dose of 2 g·kg -1·d-1 or 4 g·kg-1·d -1, or 2-VO plus rivastigmine 2 mg·kg -1·d-1. The Morris water maze test was used to assess the spatial memory retrieval. Apoptosis, total antioxide capacity (T-AOC), acetylcholine esterase (AchE) and choline acetyl transferase (ChAT) activities in the hippocampus and the cortex were investigated. Results: In the chronic cerebral hypoperfusion model, the 2-VO plus saline treatment resulted in impaired special learning as shown by the significantly prolonged escape latency and shorter swim time in the first quadrant as compared to the sham operation. The impairment was associated with apoptosis and significant decreases in T-AOC, AchE and ChAT activities in the hippocampus and the cortex. Treatment with YXQNG at either 2 g·kg-1·d-1 or 4 g·kg-1·d-1 dose, or rivastigmine resulted in significantly shorter escape latencies and longer swim time in the first quadrant. YXQNG at both doses, but not rivastigmine, had significant reduction in apoptosis, and significant increases in T-AOC and ChAT activity in both the hippocampus and the cortex. Unlike rivastigmine, neither dose of YXQNG showed significant reduction in AchE activity. Conclusions: YXQNG ameliorated cognitive impairment induced by chronic cerebral hypoperfusion. The protective effect may be mediated through its regulation of apoptosis and activities of T-AOC and ChAT in the hippocampus and cortex of the rats in the chronic cerebral hypoperfusion model, a mechanism that is different from rivastigmine.
- Acetylcholine esterase
- Choline acetyl transferase
- Chronic cerebral hypoperfusion
- Total antioxide capacity
- Yangxue Qingnao granule