中药新药与临床药理2025，Vol.36Issue(11)：1870-1876,7.DOI:10.19378/j.issn.1003-9783.2025.11.006
白芍苷调节Rac1/Akt/NF-κB信号通路对缺氧缺血性脑损伤新生大鼠神经炎症的影响
Effect of Paeoniflorin on Neuroinflammation in Neonatal Rats with Hypoxic-Ischemic Brain Damage via Modulating the Rac1/Akt/NF-κB Signaling Pathway
摘要
Abstract
Objective To investigate the effect of paeoniflorin on neuroinflammation and the Ras-related C3 botulinum toxin substrate 1/protein kinase B/nuclear factor-kappa B(Rac1/Akt/NF-κB)signaling pathway in neonatal rats with hypoxic-ischemic brain damage(HIBD).Methods A neonatal rat HIBD model was established.Successfully modeled rats were randomly divided into four groups(n=18 per group):the model group,the low-dose paeoniflorin group,the high-dose paeoniflorin group,and the high-dose paeoniflorin+phorbol ester(a pathway activator)group.An additional 18 normal neonatal rats served as the control group.After treatment,neurological deficit scores were assessed,and brain water content was measured.The levels of inflammatory factors in brain tissue were detected by enzyme-linked immunosorbent assay(ELISA).Pathological morphological changes in brain tissue were observed by hematoxylin-eosin(HE)staining.Neuronal apoptosis was detected by TUNEL staining.The protein expression levels of the Rac1/Akt/NF-κB signaling pathway and apoptosis-related proteins were measured by Western Blot.Results Compared with the control group,the model group showed disrupted brain tissue structure,significant edema,disordered neuronal arrangement,partial swelling,degeneration,necrosis,reduced neuronal count,substantial glial cell proliferation,and marked inflammatory infiltration.Neurological deficit scores,brain water content,levels of TNF-α,IL-1β,and IL-6,neuronal apoptosis rate,and the expression levels of Bax,Rac1,p-Akt/Akt,and p-NF-κB/NF-κB were significantly increased,while Bcl-2 expression was decreased(P＜0.05).Compared with the model group,the low-dose and high-dose paeoniflorin groups exhibited basically normal brain tissue structure,mild edema,relatively normal neuronal and glial cell morphology,only a small amount of neuronal degeneration and necrosis and glial cell proliferation.Their neurological deficit scores,brain water content,levels of TNF-α,IL-1β,and IL-6,neuronal apoptosis rate,and expression of Bax,Rac1,p-Akt/Akt,and p-NF-κB/NF-κB were decreased,while Bcl-2 expression was increased(P＜0.05).Compared with the high-dose paeoniflorin+phorbol ester group,the high-dose paeoniflorin group alone showed more severe brain tissue damage,disordered neuronal arrangement,reduced neuronal count,severe swelling,degeneration,and necrosis,substantial glial cell proliferation,along with increased neurological deficit scores,brain water content,levels of TNF-α,IL-1β,and IL-6,neuronal apoptosis rate,and expression of Bax,Rac1,p-Akt/Akt,and p-NF-κB/NF-κB,and decreased Bcl-2 expression(P＜0.05).Conclusion Paeoniflorin can ameliorate neuroinflammation in neonatal rats with HIBD,and its mechanism of action is associated with the inhibition of the Rac1/Akt/NF-κB signaling pathway.关键词
白芍苷/Ras相关C3肉毒素底物1/丝氨酸-苏氨酸蛋白酶/核转录因子κB信号通路/缺氧缺血性脑损伤/新生大鼠/神经炎症Key words
paeoniflorin/Rac1/Akt/NF-κB signaling pathway/hypoxic-ischemic brain damage/neonatal rats/neuroinflammation分类
医药卫生引用本文复制引用
刘淑燕,刘丹,孟莉,许坤,董沙沙..白芍苷调节Rac1/Akt/NF-κB信号通路对缺氧缺血性脑损伤新生大鼠神经炎症的影响[J].中药新药与临床药理,2025,36(11):1870-1876,7.基金项目
河北省医学科学研究课题计划项目(20240753). （20240753）
