摘要
探讨黄芪桂枝五物汤(Huangqi Guizhi Wuwu decoction,HGWD)对脑缺血损伤的保护作用及其可能机制。通过建立C57BL/6小鼠大脑中动脉闭塞(middle cerebral artery occlusion,MCAO)模型,评估HGWD对神经行为学评分、脑梗死率、脑水含量、氧化应激和炎症指标的影响。检测脑组织中核因子E2相关因子2(Nrf2)、血红素加氧酶-1(HO-1)、B细胞淋巴瘤-2(Bcl-2)和Bcl-2相关X蛋白(Bax)的mRNA及其蛋白表达水平,并利用Nrf2基因敲除小鼠验证Nrf2在HGWD改善MCAO中的作用。此外,通过神经元原代细胞氧糖剥夺/再灌注((oxygen-glucose deprivation/reperfusion,OGD/R)模型,进一步验证HGWD改善MCAO作用。结果显示,HGWD显著改善了MCAO小鼠的脑损伤,减轻氧化应激,抑制炎症因子释放,并显著上调Nrf2、HO-1和Bcl-2表达,下调Bax表达,基因表达与蛋白表达的变化趋势一致。敲除Nrf2显著减弱了HGWD的保护作用,表明Nrf2在HGWD改善脑缺血损伤中具有关键作用。体外实验表明,HGWD可显著增加OGD/R神经元细胞存活率,降低乳酸脱氢酶(LDH)漏出,减少细胞凋亡,并伴随Nrf2、HO-1、Bcl-2表达的上调和Bax表达的下调。综上,HGWD通过激活Nrf2/HO-1通路增强抗氧化能力,同时调节Bcl-2/Bax信号通路抑制细胞凋亡,从而保护脑细胞免受缺血损伤。
This study aimed to investigate the protective effects of Huangqi Guizhi Wuwu decoction(HGWD)against cerebral ischemic injury and the underlying mechanisms.A middle cerebral artery occlusion(MCAO)model was established in C57BL/6 mice to evaluate the effects of HGWD on neurobehavioral scores,cerebral infarction rate,brain water content,and oxidative stress and inflammatory markers.The mRNA and protein expression levels of nuclear factor erythroid 2-related factor 2(Nrf2),heme oxygenase-1(HO-1),B-cell lymphoma-2(Bcl-2),and Bcl-2-associated X protein(Bax)in brain tissue were assessed.In addition,Nrf2 knockout mice were used to verify the role of Nrf2 in the protective effects of HGWD against MCAO-induced injury.Additionally,an oxygen-glucose deprivation/reperfusion(OGD/R)model in primary neuronal cells was employed to further confirm the pharmacological effects of HGWD in vitro.The results showed that HGWD significantly ameliorated cerebral ischemic injury in MCAO mice,alleviated oxidative stress,suppressed the release of inflammatory factors,and markedly upregulated the expression of Nrf2,HO-1,and Bcl-2 while downregulating Bax expression,with consistent trends being observed at both mRNA and protein levels.The protective effects of HGWD were significantly attenuated in Nrf2 knockout mice,indicating the pivotal role of Nrf2 in HGWD-mediated protection against cerebral ischemic injury.In vitro experiments revealed that HGWD significantly increased neuronal cell viability,reduced lactate dehydrogenase(LDH)leakage,and decreased apoptosis in OGD/R-treated cells,accompanied by upregulation of Nrf2,HO-1,and Bcl-2 and downregulation of Bax.In conclusion,HGWD protects against cerebral ischemic injury by activating the Nrf2/HO-1 pathway to enhance antioxidant capacity and modulating the Bcl-2/Bax signaling pathway to inhibit apoptosis,thereby protecting brain cells from ischemic damage.
作者
钱程昱
王琳升
张靖
王涛
钱卫东
QIAN Chengyu;WANG Linsheng;ZHANG Jing;WANG Tao;QIAN Weidong(Department of Endocrinology,Wujin Affiliated Hospital,Nanjing University of traditional Chinese Medicine,Changzhou 213161;Department of Cardiology,Changzhou First People's Hospital,Changzhou 213004;Center for New Drug Screening and Efficacy Evaluation,State Key Laboratory of Natural Medicines,China Pharmaceutical University,Nanjing 210009;Department of Cardiology,Wujin Affiliated Hospital,Nanjing University of Traditional Chinese Medicine,Changzhou 213161,China)
出处
《中国药科大学学报》
北大核心
2026年第1期98-107,共10页
Journal of China Pharmaceutical University
基金
南京中医药大学自然科学基金项目(XZR2020092)。
