Protective effects and mechanism of puerarin on learning-memory disorder after global cerebral ischemia-reperfusion injury in rats

Objective  To observe the effect of puerarin on the learning-memory disorder after global cerebral ischemia-reperfusion injury in rats, and to explore its mechanism of action. Methods  The global cerebral ischemia-reperfusion injury model was established using the modifified Pulsinelli four-vessel occlusion in Sprague-Dawley rats. Rats were intraperitoneally injected with puerarin (100 mg/kg) 1 h before ischemia and once every 6 h afterwards. The learning-memory ability was evaluated by the passive avoidance test. The dynamic changes of the cell counts of apoptosis and positive expression of Bcl-2 in the hippocampus CA1 region were determined by the TUNEL and immunohistochemical methods, respectively. Results  (1) Compared with the reperfusion group, the step through latency (STL) in the passive avoidance test in the puerarin group was prolonged signifificantly (P<0.01). (2) The apoptotic neurons were injured most severely on the 3rd day in the hippocampal CA1 region after global ischemia and reperfusion. In the puerarin group, the number of apoptotic cells decreased at respective time points after ischemia-reperfusion (P<0.01). (3) The level of positive expression of Bcl-2 varied according to the duration of reperfusion and the peak level occurred on day 1 in the hippocampal CA1 region after global cerebral ischemia. Compared with the reperfusion group, the expression of Bcl-2 in the puerarin group was up-regulated at the respective time points after ischemia reperfusion (P<0.01), reaching the peak on day 1. Conclusions  Puerarin could improve the learning-memory ability after global cerebral ischemia and reperfusion in rats. The protective mechanism might be related to the effect of inhibiting or delaying the cell apoptosis through up-regulating the expression of Bcl-2 after ischemia and reperfusion. Supported by the Key Technologies Research and Development Program of Shaanxi Province (No. 2002k10-G2)