摘要
目的基于PI3K/AKT/NF-κB信号通路探讨益母草碱对缺血性脑卒中大鼠脑组织病理变化的影响。方法建立缺血性脑卒中大鼠模型,给予益母草碱,连续给药7天后,观察各组大鼠神经功能损害评分;检测大鼠脑组织中氧化应激指标含量;TTC染色法检测大鼠脑梗死面积百分比;HE染色法观察大鼠脑组织皮质区和海马区病理学变化情况;采用实时荧光定量聚合酶链式反应测定大鼠脑组织内梗死侧皮层血管内皮生长因子(VEGF)、低氧诱导因子1α(Hif-1α)mRNA的表达变化;Western blot检测脑组织中磷脂酰肌醇3激酶(PI3K)、丝氨酸-苏氨酸蛋白激酶(AKT)、核因子κB(NF-κB)蛋白表达。结果与空白对照组相比,模型对照组大鼠的神经功能损害评分、一氧化氮(NO)、内皮型一氧化氮合酶(eNOS)含量、VEGF和Hif-1αmRNA表达、NF-κB蛋白表达明显升高,氧化低密度脂蛋白(ox-LDL)、超氧化物歧化酶(SOD)含量、AKT、PI3K蛋白表达明显下降,差异具有统计学意义(P<0.01);与模型对照组相比,阳性对照组和益母草碱中、高剂量组大鼠的神经功能损害评分、NO、eNOS含量、VEGF和Hif-1αmRNA表达、NF-κB蛋白表达明显降低,ox-LDL、SOD含量、AKT、PI3K蛋白表达明显升高,差异具有统计学意义(P<0.01)。结论益母草碱对实验性脑损伤大鼠具有脑保护作用,可以改善脑梗死后的神经损伤,减少脑梗死体积,降低大鼠的氧化应激反应,这些效应可能是通过PI3K/AKT/NF-κB信号通路实现的。
Aim To investigate the effect of leonurine on the pathological changes of cerebral tissue in rats with ischemic stroke based on PI3 K/AKT/NF-κB signaling pathway.Methods The rat model of ischemic stroke was established,and leonurine was administered continuously for 7 days.The neurological impairment score of each group was observed.The content of oxidative stress index was detected in rat brain tissue.The percentage of cerebral infarction area in rats was detected by TTC staining.HE staining was used to observe the pathological changes in cortex and hippocampus of rat brain.The expressions of vascular endothelial growth factor(VEGF)and hypoxia-inducibal factor 1α(Hif-1α)in cerebral infarction cortex of rats were measured by real-time fluorescence quantitative polymerase chain reaction.Western blot was used to detect the protein expressions of phosphatidyl inositol-3-kinase(PI3 K),serine-threonine protein kinase(AKT)and nuclear factor-κB(NF-kappa B)in brain tissue.Results Compared with the blank control group,the neurological impairment score,the contents of nitric oxide(NO)and endothelial nitric oxide synthase(eNOS),mRNA expressions of VEGF and Hif-1αand protein expression of NF-κB were increased significantly,the contents of oxidized low density lipoprotein(ox-LDL)and superoxide dismutase(SOD),and protein expressions of AKT and PI3 K were decreased significantly in rats of model control group;The differences had statistical significance(P<0.01).Compared with the model control group,the neurological impairment score,the contents of NO and eNOS,mRNA expressions of VEGF and Hif-1αand protein expression of NF-κB were decreased significantly,the contents of ox-LDL and SOD,and protein expressions of AKT and PI3 K were increased significantly in rats of positive control group and middle-and high-dose leonurine group;The differences had statistical significance(P<0.01).Conclusions Leonurine has brain protective effect on rats with experimental brain injury.It can improve nerve injury after cerebral infarction,reduce the volume of cerebral infarction and reduce oxidative stress response.These effects may be achieved through PI3 K/AKT/NF-κB signaling pathway.
作者
杜帅
刘佳
刘婷
李丹
房江山
马娜
孟新玲
DU Shuai;LIU Jia;LIU Ting;LI Dan;FANG Jiangshan;MA Na;MENG Xinling(Department of Neurology,Xinjiang Uygur Autonomous Region Hospital of TraditionalChinese Medicine,Urumqi,Xinjiang830099,China;Department of Encephalopathy,Xinjiang Uygur Autonomous Region Hospital of TraditionalChinese Medicine,Urumqi,Xinjiang830099,China)
出处
《中国动脉硬化杂志》
CAS
2019年第10期853-861,共9页
Chinese Journal of Arteriosclerosis
