Xiao Jie, Wu Min, Li Hailong, Zhang Shufan, Deng Jing, Wu Bihua
Department of Internal Medicine, Nanchong Mental Health Center Nanchong 637000, Sichuan, China.
Innovation Centre for Science and Technology, North Sichuan Medical College Nanchong 637000, Sichuan, China.
Am J Transl Res. 2025 Feb 15;17(2):1223-1236. doi: 10.62347/NWQS1671. eCollection 2025.
It is postulated that oxidative stress and pyroptosis, which are induced by chronic cerebral hypoperfusion (CCH), contribute to the pathogenesis of vascular cognitive impairment (VCI). The protective role of TIGAR in neurologic illnesses has been the subject of extensive examination, yet its role in models of CCH-induced cognitive impairment remains unexplored. The objective of this study was to ascertain whether TIGAR is a neuroprotective agent in rats with CCH that reduces oxidative stress and pyroptosis.
A CCH model was established in rats through the use of bilateral common carotid artery occlusion (BCCAO). The effects of TIGAR on cognitive function and anxiety-depressive behaviors in rats with CCH were examined. To this end, the Y-maze and open field tests were employed. Nissl and hematoxylin-eosin (H&E) staining were used to assess histologic changes in the CA1 area of the hippocampus. Hippocampal glutathione (GSH) activity, malondialdehyde (MDA) content, and NADPH/NADP+ ratio were measured using the WST-8 colorimetric method to assess oxidative stress. The expression of TIGAR and pyroptosis-related proteins was assessed by western blotting.
A model of CCH-induced cognitive impairment was successfully established. Four weeks after BCCAO, cerebral blood flow returned to normal in the rats, and cognitive impairment and anxiety-depression-like behavior developed. In rats with CCH, MDA levels increased, GSH activity and NADPH/NADP+ ratio decreased, and pyroptosis-related protein expression increased. The pathologic findings indicated that there was an exacerbation of neuronal injury in the CA1 area of the hippocampus and that the cells were loosely arranged. In rats with CCH, overexpression of TIGAR reduced pyroptosis-associated protein expression while increasing MDA content, GSH activity, and NADPH/NADP+ ratio. It promoted neuronal cell survival, and improved cognitive function and anxiety-depression-like behavior.
Overexpression of TIGAR reduced CCH-induced oxidative stress and pyroptosis and ameliorated cognitive dysfunction and anxiety-depression-like behavior in rats. These findings suggest that TIGAR counteracts oxidative stress and prevents pyroptosis, making it a promising target for the treatment of VCI.
据推测，慢性脑灌注不足（CCH）所诱导的氧化应激和细胞焦亡促成了血管性认知障碍（VCI）的发病机制。TIGAR在神经疾病中的保护作用已成为广泛研究的主题，但其在CCH诱导的认知障碍模型中的作用仍未得到探索。本研究的目的是确定TIGAR在CCH大鼠中是否为一种神经保护剂，可减轻氧化应激和细胞焦亡。
通过双侧颈总动脉闭塞（BCCAO）在大鼠中建立CCH模型。检测TIGAR对CCH大鼠认知功能和焦虑抑郁行为的影响。为此，采用了Y迷宫和旷场试验。使用尼氏染色和苏木精-伊红（H&E）染色评估海马CA1区的组织学变化。采用WST-8比色法测定海马谷胱甘肽（GSH）活性、丙二醛（MDA）含量和NADPH/NADP+比值，以评估氧化应激。通过蛋白质免疫印迹法评估TIGAR和细胞焦亡相关蛋白的表达。
成功建立了CCH诱导的认知障碍模型。BCCAO术后四周，大鼠脑血流量恢复正常，出现认知障碍和焦虑抑郁样行为。在CCH大鼠中，MDA水平升高，GSH活性和NADPH/NADP+比值降低，细胞焦亡相关蛋白表达增加。病理结果表明，海马CA1区神经元损伤加剧，细胞排列疏松。在CCH大鼠中，TIGAR的过表达降低了细胞焦亡相关蛋白的表达，同时增加了MDA含量、GSH活性和NADPH/NADP+比值。它促进了神经元细胞的存活，并改善了认知功能和焦虑抑郁样行为。
TIGAR的过表达减轻了CCH诱导的氧化应激和细胞焦亡，并改善了大鼠的认知功能障碍和焦虑抑郁样行为。这些发现表明，TIGAR可对抗氧化应激并防止细胞焦亡，使其成为治疗VCI的一个有前景的靶点。
