基于Notch1/NF-κB信号轴探讨败酱草总黄酮对大鼠脑缺血耐受模型炎症级联反应的影响  

Inflammatory Effect of Total Flavonoids from Patrinia scabiosifolia on Rats with Brain Ischemic Tolerance Based on Notch1/NF-kB Signaling Axis

作　　者：王灿[1] 张思森 苗明三[2] 李秀敏 武香香[2] WANG Can;ZHANG Sisen;MIAO Mingsan;LI Xiumin;WU Xiangxiang(The Fifth People's Hospital of Henan University of Chinese Medicine,Zhengzhouu 450046;Henan University of Chinese Medicine,Zhengzhou 450046)

机构地区：[1]河南中医药大学第五临床医学院,郑州450046 [2]河南中医药大学,郑州450046

出　　处：《中药药理与临床》2023年第8期67-71,共5页Pharmacology and Clinics of Chinese Materia Medica

基　　金：中原学者工作站项目(编号:224400510011);2022年河南省博士后科研资助项目(编号:284966);博士基金项目(编号:00104354-2018-6);河南省高等学校重点科研项目(编号:22B360008);河南省优秀青年科学基金项目(编号:212300410057)。

摘　　要：目的:研究败酱草总黄酮对大鼠脑缺血耐受模型炎症级联反应的影响。方法:采用阻断大鼠双侧颈总动脉(CCA)10 min作为缺血预处理,再灌注120 h后,线栓阻塞法阻断左侧大脑中动脉2 h,再复灌22 h,建立大鼠脑缺血耐受模型。于第1次缺血预处理开始,连续灌药7 d。末次给药后,取脑部中间位置,观察脑组织梗死面积;ELISA法测定脑组织匀浆白介素-1(IL-1)、IL-10、肿瘤坏死因子-a(TNF-α)、转化生长因子-β(TGF-β)、基质金属蛋白酶-2(MMP-2)、MMP-9、低氧诱导因子(HIF-1)和热休克蛋白70(HSP70)含量;免疫组化法检测皮质区Notch信号受体1(Notch1)和核转录因子κB-p65(NF-κB p65)的蛋白表达。结果:与正常对照组比较,模型对照组脑梗死面积,脑组织IL-1、TNF-α、MMP-2、MMP-9、TGF-β、HIF-1、HSP70含量及其脑皮质区Notch1、NF-κBp65蛋白表达均显著升高(P<0.01);与模型对照组比较,败酱草总黄酮200 mg/kg组能够明显降低脑梗死面积(P<0.05),败酱草总黄酮100、200 mg/kg组能明显降低IL-1、TNF-α、MMP-2、MMP-9含量(P<0.05),200 mg/kg组能显著升高TGF-β、IL-10、HIF-1、HSP70含量(P<0.05);败酱草总黄酮200 mg/kg组Notch1、NF-κBp65蛋白表达显著下调(P<0.01),败酱草总黄酮100 mg/kg组Notch1、NF-κBp65蛋白表达明显下调(P<0.05或P<0.01)。结论:败酱草总黄酮能调控脑缺血后体内促炎因子和抗炎因子的失衡状态,抑制炎症级联反应,减轻脑组织损伤,发挥脑保护作用。Objective:To explore the effect of total flavonoids from Patrinia scabiosifolia on the rat model of brain ischemic tolerance(BIT).Methods:The bilateral common carotid artery was blocked for 10 min to induce ischemia,and then rats were restored perfusion for 120 hours.The left middle cerebral artery was blocked by thread occlusion method for 2 hours,and then rats were restored perfusion for 22 hours to establish the model of BIT.The rats were administrated by gavage with total flavonoids from P.scabiosifolia for 7 days.After the last administration,the infarct areas of brain tissue were observed.The levels of interleukin-1(IL-1),interleukin-10(IL-10),tumor necrosis factor-α(TNF-α),transforming growth factor-β(TGF-β),matrix metalloproteinase(MMP)-2,MMP-9,hypoxia inducible factor-1(HIF-1),and HSP70 were detected in the brain tissue homogenate by enzyme-linked immunosorbent assay(ELISA).The protein expression levels of Notchl and NFkBp65 in brain tissues were detected by immunohistochemistry.Results:As compared with the normal control group,the cerebral infarction areas,the levels of IL-1,TNF-α,MMP-2,MMP-9,TGF-β,IL-10,HIF-1,and HSP70,and the expression levels of Notch1 and NF-kBp65 in the cerebral cortex were significantly increased(P<0.01).As compared with the model group,200 kg/mg total flavonoids from P.scabiosifolia significantly decreased the area of cerebral infarction,the 200 and 100 mg/kg total flavonoids from P.scabiosifolia reduced the content of IL-1,TNF-α,MMP-2,and MMP-9(P<0.05),the 200 mg/kg total flavonoids from P.scabiosifolia increased the levels of TCF-β,IL-10,HIF-1 and HSP70(P<0.05).The 200 mg/kg total flavonoids from P.scabiosifolia significantly down-regulated the protein expression levels of Notch1 and NF-kBp65(P<0.01),and 100 mg/kg down-regulated the expression of Notch1 and NF-kBp65(P<0.05 or P<0.01).Conclusion:The total flavonoids from P.scabiosifolia may correct the imbalance of pro-inflammatory and anti-inflammatory factors after cerebral ischemia,inhibit inflammatory reaction,and re

关 键 词：败酱草总黄酮 脑缺血耐受模型 炎症 Notch信号受体1/核转录因子κB-p65信号轴 

分 类 号：R285.5[医药卫生—中药学]