Li Meixi, Song Jiaxi, Niu Xiaoli, Mo Feng, Xie Xiaohua, Li Xiuqin, Yin Yu, Wang Tianjun, Song Xiujuan, Liu Jingze, Lv Peiyuan
Postdoctoral Innovation Practice Base of Hebei General Hospital, Shijiazhuang, Hebei, China.
Postdoctoral Research Station of Biology, Hebei Normal University, Shijiazhuang, Hebei, China.
Front Aging Neurosci. 2025 Apr 11;17:1521353. doi: 10.3389/fnagi.2025.1521353. eCollection 2025.
The potential for therapeutic strategies that promote angiogenesis and suppress neuroinflammation to ameliorate cognitive decline induced by chronic cerebral hypoperfusion (CCH) has led to their recognition as promising therapeutic targets for vascular dementia (VD). The SIRT1-mediated Notch1 signaling pathway is important in regulating angiogenesis and neuroinflammation. Previous studies have demonstrated that baicalein alleviates cognitive decline in rats with CCH. Nevertheless, it remains unclear whether baicalein can stimulate angiogenesis in the context of VD and whether this cognitive protective effect is achieved by regulating the SIRT1-mediated Notch1 pathway. The aim of this study was to investigate the impact and the underlying mechanism of baicalein on angiogenesis and neuroinflammation in rats with CCH.
Adult Sprague-Dawley (SD) rats were administered baicalein or a SIRT1 inhibitor. Cognitive function was assessed by the Morris water maze (MWM) test, and angiogenesis was assessed by immunohistochemical analysis of microvascular density (MVD) and the number of CD31+/5-bromo-2'-deoxyuridine (BrdU)+ cells. Neuroinflammation and apoptosis were assessed by immunohistochemistry for GFAP, Iba-1, NEUN/cleaved caspase-3, and ELISA analysis for TNF-α and IL-1β. Additionally, Western blotting was employed to evaluate the expression of the SIRT1-mediated Notch1 pathway.
The results demonstrated that baicalein ameliorated memory and learning deficits in rats following CCH by promoting angiogenesis and suppressing neuroinflammation. However, this protective effect could be reversed by inhibiting SIRT1. Baicalein was observed to up-regulate the expression of SIRT1 and down-regulate the Notch1-related molecules.
The SIRT1-related pathway plays a crucial role in regulating angiogenesis and neuroinflammation. Moreover, baicalein exerts a neuroprotective effect against cognitive decline through the SIRT1-mediated Notch1 pathway, which in turn improves angiogenesis and suppresses neuroinflammation.
促进血管生成和抑制神经炎症的治疗策略改善慢性脑灌注不足（CCH）所致认知功能下降的潜力，使其被视为血管性痴呆（VD）有前景的治疗靶点。SIRT1介导的Notch1信号通路在调节血管生成和神经炎症中起重要作用。先前研究表明，黄芩苷可减轻CCH大鼠的认知功能下降。然而，黄芩苷在VD背景下是否能刺激血管生成以及这种认知保护作用是否通过调节SIRT1介导的Notch1通路实现仍不清楚。本研究旨在探讨黄芩苷对CCH大鼠血管生成和神经炎症的影响及潜在机制。
成年Sprague-Dawley（SD）大鼠给予黄芩苷或SIRT1抑制剂。通过莫里斯水迷宫（MWM）试验评估认知功能，通过微血管密度（MVD）免疫组化分析和CD31+/5-溴-2'-脱氧尿苷（BrdU）+细胞数量评估血管生成。通过GFAP、Iba-1、NEUN/裂解的半胱天冬酶-3免疫组化和TNF-α及IL-1β ELISA分析评估神经炎症和细胞凋亡。此外，采用蛋白质免疫印迹法评估SIRT1介导的Notch1通路的表达。
结果表明，黄芩苷通过促进血管生成和抑制神经炎症改善CCH后大鼠的记忆和学习缺陷。然而，抑制SIRT1可逆转这种保护作用。观察到黄芩苷上调SIRT1表达并下调Notch1相关分子。
SIRT1相关通路在调节血管生成和神经炎症中起关键作用。此外，黄芩苷通过SIRT1介导的Notch1通路对认知功能下降发挥神经保护作用，进而改善血管生成并抑制神经炎症。
