益气升清方调节HIF-1α/NLRP3信号通路对缺血性脑卒中大鼠神经元焦亡的影响  

Influence of Yiqi Shengqing recipe on neuron pyroptosis in ischemic stroke rats by regulating HIF-1α/NLRP3 signal pathway

作　　者：王月 权兴苗[1] 王玉 宋春侠[1] 邵月 徐立伟[1] WANG Yue;QUAN Xingmiao;WANG Yu;SONG Chunxia;SHAO Yue;XU Liwei(Department of Traditional Chinese Medicine,the Affiliated Hospital of Chengde Medical University Chengde 067000,China;Department of Acupuncture and Massage,Chengde Hospital of Traditional Chinese Medicine;Department of Orthopedics and Traumatology,the Affiliated Hospital of Chengde Medical University)

机构地区：[1]承德医学院附属医院中医科,067000 [2]承德市中医院针灸推拿科 [3]承德医学院附属医院骨伤科

出　　处：《天津医药》2024年第4期350-355,共6页Tianjin Medical Journal

基　　金：河北省中医药管理局科研计划项目(2022154)。

摘　　要：目的 探究益气升清方调节缺氧诱导因子-1α(HIF-1α)/NOD样受体热蛋白结构域相关蛋白3(NLRP3)信号通路对缺血性脑卒中大鼠神经元焦亡的影响。方法 将SD大鼠随机分为假手术组(S组),模型组(M组),益气升清方低、中、高剂量组(3.465、6.930、13.860 g/kg)及益气升清方高剂量+HIF-1α激活剂DMOG组(13.860 g/kg益气升清方+40 mg/kg DMOG),每组15只。采用线栓法构建脑卒中模型。造模成功后进行神经功能缺陷评估;TTC染色评估脑梗死体积;ELISA法检测血清白细胞介素(IL)-1β、IL-18水平;HE染色检测缺血皮质区病理变化;TUNEL染色检测神经元凋亡;Western blot检测焦亡及HIF-1α/NLRP3通路相关蛋白表达。结果 与S组比较,M组神经功能缺陷评分、梗死体积、IL-1β含量、IL-18含量、神经细胞凋亡率、胞膜穿孔蛋白D-N端(GSDMD-N)、胱天蛋白酶1(Caspase-1)、HIF-1α、NLRP3蛋白水平均上升(P<0.05);与M组比较,低、中、高剂量益气升清方组神经功能缺陷评分、梗死体积、IL-1β含量、IL-18含量、神经细胞凋亡率、GSDMD-N、Caspase-1、HIF-1α、NLRP3蛋白水平均下调(P<0.05);DMOG减弱了高剂量益气升清方对缺血性脑卒中大鼠神经元焦亡的改善作用。结论 益气升清方可能通过下调HIF-1α/NLRP3信号通路减轻缺血性脑卒中大鼠神经元焦亡。Objective To investigate the influence of Yiqi Shengqing recipe on neuronal pyroptosis in ischemic stroke rats by regulating hypoxia inducible factor-1α(HIF-1α)/NOD-like receptor thermal protein domain associated protein 3(NLRP3)signal pathway.Methods SD rats were randomly divided into the sham operation group(S group),the model group(M group),the low,medium and high dose(3.465,6.930 and 13.860 g/kg)Yiqi Shengqing recipe groups,and high dose Yiqi Shengqing recipe+HIF-1αactivator DMOG(13.860 g/kg Yiqi Shengqing recipe+40 mg/kg DMOG)group,15 animals in each group.The stroke model was constructed by thread plug method.After successful modeling,neural function defects were evaluated including TTC staining for evaluating the volume of cerebral infarction,ELISA for detecting the serum interleukin(IL)-1βand IL-18 levels,HE staining for detecting pathological changes of ischemic cortex,TUNEL staining for detecting neuronal apoptosis and Western blot assay for detecting the expression of pyroprotein and HIF-1α/NLRP3 pathway protein.Results Compared with the S group,the neurological deficit score,infarct volume,IL-1β,IL-18 contents,apoptosis rate of nerve cells,GasderminD-N(GSDMD-N),Caspase-1,HIF-1αand NLRP3 protein levels were increased in the M group(P<0.05).Compared with the M group,the neurological defect score,infarct volume,IL-1β,IL-18 contents,neuronal apoptosis rate,GSDMD-N,Caspase-1,HIF-1αand NLRP3 protein levels were decreased in the low,medium and high dose Yiqi Shengqing recipe groups(P<0.05).DMOG attenuated the improvement effect of high-dose Yiqi Shengqing recipe on neuronal death in ischemic stroke rats.Conclusion Yiqi Shengqing recipe may reduce the neuronal pyroptosis in ischemic stroke rats by down-regulating HIF-1α/NLRP3 signal pathway.

关 键 词：卒中 缺氧诱导因子1 Α亚基 NLR家族 热蛋白结构域包含蛋白3 神经元 细胞焦亡 益气升清方 

分 类 号：R285.5[医药卫生—中药学]