Department of Neurology, the Second Affiliated Hospital of Guangxi Medical University, Nanning 530007, Guangxi Zhuang Autonomous Region, China.
Department of Urology, National Hospital of Guangxi Zhuang Autonomous Region, Nanning 530001, Guangxi Zhuang Autonomous Region, China.
J Tradit Chin Med. 2021 Feb;41(1):133-139. doi: 10.19852/j.cnki.jtcm.2021.01.015.
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.
研究丹参酮Ⅱ A（TSA）联合间充质干细胞（MSCs）治疗血管性痴呆（VaD）引起的学习记忆障碍的疗效，并探讨其作用机制。
采用改良四血管闭塞法制备 VaD 大鼠模型，通过 Morris 水迷宫检测大鼠空间学习记忆能力。将大鼠随机分为 MSCs 组、TSA 组、MSCs 联合 TSA 组、模型组和假手术组。苏木精-伊红（HE）染色观察海马组织病理学改变，流式细胞术检测海马神经元凋亡率，Western blot 法检测 Bcl-2、Bax 蛋白表达，检测大鼠海马组织活性氧（ROS）水平及总超氧化物歧化酶（T-SOD）活性。
尾静脉注射联合给药可明显改善 VaD 模型大鼠认知功能障碍，与模型组比较差异有统计学意义（P<0.01），其保护作用强于单独应用 MSCs 或 TSA；联合用药可协同抑制全脑缺血诱导的大鼠海马神经元凋亡，上调抗凋亡蛋白 Bcl-2 表达，下调促凋亡蛋白 Bax 表达；联合用药还可减轻大鼠海马组织 ROS 生成，增强 T-SOD 活性，其抗氧化作用强于单独应用 MSCs 或 TSA。
TSA 联合 MSCs 治疗可通过抑制海马神经元凋亡和抗氧化作用改善 VaD 模型大鼠的空间学习记忆能力，且联合治疗的效果优于单独应用 MSCs 或 TSA。
