Yin Ya-Ling, Liu Yan-Hua, Zhu Mo-Li, Wang Huan-Huan, Qiu Yue, Wan Guang-Rui, Li Peng
School of Basic Medical Sciences, Department of Physiology and Pathophysiology, Sino-UK Joint Laboratory of Brain Function and Injury and Department of Physiology and Neurobiology, Xinxiang Medical University,Xinxiang, China, 453003; College of Pharmacy, Henan international joint laboratory of cardiovascular remodeling and drug intervention, Xinxiang key laboratory of vascular remodeling intervention and molecular targeted therapy drug development, Xinxiang Medical University,Xinxiang, China, 453003.
College of Pharmacy, Henan international joint laboratory of cardiovascular remodeling and drug intervention, Xinxiang key laboratory of vascular remodeling intervention and molecular targeted therapy drug development, Xinxiang Medical University,Xinxiang, China, 453003.
Physiol Behav. 2022 May 15;249:113777. doi: 10.1016/j.physbeh.2022.113777. Epub 2022 Mar 8.
Vascular dementia (VD) is the second largest type of dementia after Alzheimer's disease. At present, the pathogenesis is complex and there is no effective treatment. Floralozone has been shown to reduce atherosclerosis in rats caused by a high-fat diet. However, whether it plays a role in VD remains elusive. In the present study, the protective activities and relevant mechanisms of Floralozone were evaluated in rats with cognitive impairment, which were induced by bilateral occlusion of the common carotid arteries (BCCAO) in rats. Cognitive function, pathological changes and oxidative stress condition in the brains of VD rats were assessed using Neurobehavioral tests, Morris water maze tests, hematoxylin-eosin staining, Neu N staining, TUNEL staining, Golgi staining, Western blot assay and antioxidant assays (MDA, SOD, GSH), respectively. The results indicated that VD model was established successfully and BCCAO caused a decline in spatial learning and memory and hippocampal histopathological abnormalities of rats. Floralozone (50, 100, 150 mg/kg) dose-dependently alleviated the pathological changes, decreased oxidative stress injury, which eventually reduced cognitive impairment in BCCAO rats. The same results were shown in further experiments with neurobehavioral tests. At the molecular biological level, Floralozone decreased the protein level of transient receptor potential melastatin-related 2 (TRPM2) in VD and normal rats, and increased the protein level of NR2B in hippocampus of N-methyl-D-aspartate receptor (NMDAR). Notably, Floralozone could markedly improved learning and memory function of BCCAO rats in Morris water maze (MWM) and improved neuronal cell loss, synaptic structural plasticity. In conclusion, Floralozone has therapeutic potential for VD, increased synaptic structural plasticity and alleviating neuronal cell apoptosis, which may be related to the TRPM2/NMDAR pathway.
血管性痴呆（VD）是仅次于阿尔茨海默病的第二大类型痴呆。目前，其发病机制复杂，尚无有效治疗方法。已证明花氧酮可减轻高脂饮食诱导的大鼠动脉粥样硬化。然而，其在VD中是否发挥作用仍不清楚。在本研究中，在双侧颈总动脉闭塞（BCCAO）诱导的认知功能障碍大鼠中评估了花氧酮的保护作用及相关机制。分别使用神经行为测试、莫里斯水迷宫测试、苏木精-伊红染色、Neu N染色、TUNEL染色、高尔基染色、蛋白质免疫印迹分析和抗氧化分析（丙二醛、超氧化物歧化酶、谷胱甘肽）评估VD大鼠大脑的认知功能、病理变化和氧化应激状况。结果表明成功建立了VD模型，BCCAO导致大鼠空间学习和记忆能力下降以及海马组织病理学异常。花氧酮（50、100、150mg/kg）剂量依赖性地减轻了病理变化，降低了氧化应激损伤，最终减轻了BCCAO大鼠的认知障碍。神经行为测试的进一步实验也显示了相同结果。在分子生物学水平上，花氧酮降低了VD大鼠和正常大鼠中瞬时受体电位香草酸亚型2（TRPM2）的蛋白水平，并增加了N-甲基-D-天冬氨酸受体（NMDAR）海马体中NR2B的蛋白水平。值得注意的是，花氧酮可显著改善BCCAO大鼠在莫里斯水迷宫（MWM）中的学习和记忆功能，并改善神经元细胞丢失、突触结构可塑性。总之，花氧酮对VD具有治疗潜力，可增加突触结构可塑性并减轻神经元细胞凋亡，这可能与TRPM2/NMDAR通路有关。
