黑龙江医药科学

目的：探讨EGb对脑缺血再灌注损伤(CIRI)作用的机制。方法：应用网络药理学筛选EGb和脑缺血再灌注损伤(IRI)交叉靶点，进行KEGG通路富集分析。SD大鼠随机分为Sham组、CIRI组、ALT711组、EGb组和EGb+ALT711组，制作CIRI模型观察脑皮质病理变化，免疫组织化学法检测脑皮质AGEs和RAGE的表达，Western blot检测脑皮质AGEs、RAGE、FTH、GPX4和SCL7A11的表达，验证网络药理学分析结果。结果：网络药理学结果显示，EGb可通过AGEs/RAGE信号通路对脑缺血再灌注损伤起作用。动物实验结果显示，与CIRI组比较，EGb组和ALT711组大鼠脑组织病理损伤减轻，AGEs和RAGE的表达减少(P<0.05),FTH、GPX4和SCL7A11表达增多(P<0.05);与ALT711组比较，EGb+ALT711组大鼠脑组织病理损伤减轻，AGEs和RAGE的表达减少(P<0.05),FTH、GPX4和SCL7A11表达增多(P<0.05)。结论：EGb可通过AGEs/RAGE信号通路改善铁死亡介导的CIRI。

Objective: To investigate the mechanism of Ginkgo biloba extract(EGb) on cerebral ischemia-reperfusion injury(CIRI). Methods: Network pharmacology was applied to screen the overlapping targets of EGb and CIRI, followed by KEGG pathway enrichment analysis. SD rats were randomly divided into Sham, CIRI, ALT711, EGb and EGb+ALT711 groups. A CIRI model was established to observe pathological changes in the cerebral cortex. Immunohistochemistry was used to detect the expression of advanced glycation end products(AGEs) and receptor for AGEs(RAGE) in the cerebral cortex, while Western blot was employed to measure the expression of AGEs, RAGE, ferritin heavy chain(FTH), glutathione peroxidase 4(GPX4), and solute carrier family 7 member 11(SCL7A11) in the cerebral cortex to validate the results of network pharmacology analysis. Results: Network pharmacology results showed that EGb may exert its effects on CIRI through the AGEs/RAGE signaling pathway. Animal experimental results demonstrated that, compared with the CIRI group, the EGb and ALT711 groups exhibited reduced pathological damage in brain tissue, decreased expression of AGEs and RAGE, and increased expression of FTH, GPX4 and SCL7A11(P<0.05). Compared with the ALT711 group, the EGb+ALT711 group showed further alleviated pathological damage in brain tissue, reduced expression of AGEs and RAGE, and elevated expression of FTH, GPX4 and SCL7A11(P<0.05). Conclusion: EGb can improve ferroptosis-mediated CIRI through the AGEs/RAGE signaling pathway.