Efficacy of tanshinone IIA and mesenchymal stem cell treatment of learning and memory impairment in a rat model of vascular dementia.

Abstract

To investigate the efficacy of administration of tanshinone Ⅱ A (TSA) combined with mesenchymal stem cells (MSCs) for the treatment of learning and memory impairment caused by vascular dementia (VaD) and to determine the underlying mechanism. Modified four-vessel occlusion was used to establish a VaD model in rats, and their spatial learning and memory capacity was assessed by the Morris water maze. The rats were randomized into MSCs, TSA, MSCs combined with TSA, vehicle and sham groups. Histological changes were determined by hematoxylin and eosin staining, and the hippocampal neuron apoptosis ratio was assessed by flow cytometry. Western blotting was performed to detect Bcl-2 and Bax expression. The reactive oxidative species (ROS) levels and the activity of total superoxide dismutase (T-SOD), an antioxidant enzyme in the rat hippocampus, were determined. TSA combined with MSCs treatment administered by intravenous injection in the tail significantly attenuated cognitive deficits in the VaD model compared with the vehicle group (P < 0.01), and its protective effect on cognitive function was greater than that obtained by treatment with MSCs or TSA alone. Furthermore, TSA combined with MSCs treatment achieved synergistic effects in suppressing neuronal apoptosis in the rat hippocampus caused by global brain ischemia via up-regulating the expression of Bcl-2, an anti-apoptosis protein, and decreasing the expression of Bax, a pro-apoptotic protein. In addition, TSA combined with MSCs treatment attenuated ROS production and enhanced T-SOD activity in the rat hippocampus, and the antioxidant effect was greater than that of treatment with MSCs or TSA alone. TSA combined with MSCs treatment improved the spatial learning and memory capacity in a VaD model via suppressing neuronal apoptosis and antioxidant activity in the hippocampus, and this improvement was greater with combined treatment than with treatment with MSCs or TSA alone.