毛蕊异黄酮介导IκB/NF-κB信号通路对大鼠脑缺血再灌注损伤的保护作用
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摘要
目的探讨毛蕊异黄酮对脑缺血再灌注模型大鼠的神经保护作用。方法 100只雄性SD大鼠分脑缺血再灌注模型组,毛蕊异黄酮高、中、低剂量组和假手术组。采用大脑中动脉栓塞(MCAO)建立局灶性脑缺血再灌注模型,观察缺血再灌注后,各组大鼠在神经行为学、脑梗死体积、脑含水量及脑组织中超氧化物歧化酶(SOD)、丙二醛(MDA)、IκB mRNA、核转录因子-κB(NF-κB)mRNA、IκBα蛋白、NF-κB p65蛋白表达的差异。结果毛蕊异黄酮能够改善大鼠神经行为损伤,降低脑梗死体积和脑组织含水量,抑制脑组织中MDA生成,提高SOD的活性,增加IκB mRNA和IκBα蛋白的表达,减少NF-κB mRNA和NF-κB p65蛋白的表达。结论毛蕊异黄酮对大鼠脑缺血再灌注损伤具有保护作用。
Objective To explore the neuroprotective effect of calycosin in rats after cerebral ischemia and reperfusion.Methods 100 male SD rats were randomly divided into the sham group,the ischemia reperfusion group,the high-,middle-,low-dose of calycosin group.The model of focal cerebral ischemia and reperfusion was constructed through middle cerebral artery occlusion(MCAO).We observed the differences on neural behavior,infarction volume,brain water content,superoxide(SOD),maloneliadehyde(MDA),IκB mRNA,nucleartranscription factor-κB(NF-κB)mRNA,IκBαprotein,NF-κB p65 protein of brain tissue.Results Calycosin improved the neurobehavioral impairment,reduced the infarction volume and water content.And it inhibited the production of MDA and enhanced the activation of SOD,promoted the production of IκB in mRNA and protein.Conclusion Calycosin had protective effects in cerebral ischemia reperfusion rats.
Objective To explore the neuroprotective effect of calycosin in rats after cerebral ischemia and reperfusion.Methods 100 male SD rats were randomly divided into the sham group,the ischemia reperfusion group,the high-,middle-,low-dose of calycosin group.The model of focal cerebral ischemia and reperfusion was constructed through middle cerebral artery occlusion(MCAO).We observed the differences on neural behavior,infarction volume,brain water content,superoxide(SOD),maloneliadehyde(MDA),IκB mRNA,nucleartranscription factor-κB(NF-κB)mRNA,IκBαprotein,NF-κB p65 protein of brain tissue.Results Calycosin improved the neurobehavioral impairment,reduced the infarction volume and water content.And it inhibited the production of MDA and enhanced the activation of SOD,promoted the production of IκB in mRNA and protein.Conclusion Calycosin had protective effects in cerebral ischemia reperfusion rats.
引文
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[2]SUN H T,YIN M F,QIAN W Q,et al.Calycosin,aphytoestrogen isoflavone,induces apoptosis of estrogen receptor-positive MG-63osteosarcoma cells via the phosphatidylinositol 3-kinase(PI3K)/AKT/mammalian target of rapamycin(mTOR)pathway[J].Med Sci Monit,2018,24:6178-6186.
[3]李晶晶,崔国祯,王亮,等.毛蕊异黄酮对H9c2细胞缺糖缺氧损伤的保护作用[J].中药药理与临床,2014,30(5):32-35.
[4]TSIVGOULIS G,KATSANOS A H,ALEXANDROV AV.Reperfusion therapies of acute ischemic stroke:potentials and failures[J].Front Neurol,2014,5:215.
[5]CAI Y,XU H,YAN J,et al.Molecular targets and mechanism of action of dexmedetomidine in treatment of ischemia/reperfusion injury[J].Mol Med Rep,2014,9(5):1542-1550.
[6]姚瀚勋,唐乐剑,夏学巍,等.不同剂量伊桐苷灌胃对大鼠弥散性脑损伤的防治作用及其机制[J].山东医药,2016,56(15):19-22.
[7]王文波,夏学巍,唐乐剑,等.伊桐抗氧化作用的实验研究[J].中药药理与临床,2016,32(3):105-109.
[8]WANG Y,REN Q Y,ZHANG X,et al.Neuroprotective mechanisms of calycosin against focal cerebral ischemia and reperfusion injury in rats[J].Cell Physiol Biochem,2018,45(2):537-546.
[9]GUO C,MA Y Y,MA S B,et al.The role of TRPC6in the neuroprotection of calycosin against cerebral ischemic injury[J].Sci Rep,2017,7(1):3039.
[10]FU S P,GU Y,JIANG J Q,et al.Calycosin-7-O-β-D-glucoside regulates nitric oxide/caveolin-1/matrix metalloproteinases pathway and protects blood-brain barrier integrity in experimental cerebral ischemia-reperfusion injury[J].J Ethnopharmacol,2014,155(1):692-701.
[11]RIDDER D A,SCHWANINGER M.NF-kappaB signaling in cerebral ischemia[J].Neuroscience,2009,158(3):995-1006.
[12]杨美丽,黄银辉,姚力,等.慢性间断性缺氧对大鼠脑缺血再灌注NF-κB及其靶基因TNF-α表达的影响[J].第三军医大学学报,2014,36(12):1303-1306.
[13]CUI H X,CHEN J H,LI J W,et al.Protection of anthocyanin from myrica rubra against cerebral ischemia-reperfusion injury via modulation of the TLR4/NF-κB and NL-RP3pathways[J].Molecules,2018,23(7):E1788.
[14]WICHA P,TOCHARUS J,JANYOU A,et al.Hexahydrocurcumin protects against cerebral ischemia/reperfusion injury,attenuates inflammation,and improves antioxidant defenses in a rat stroke model[J].PLoS One,2017,12(12):e0189211.
[15]WANG X R,AN F,WANG S L,et al.Orientin attenuates cerebral ischemia/reperfusion injury in rat model through the AQP-4and TLR4/NF-κB/TNF-αsignaling pathway[J].J Stroke Cerebrovasc Dis,2017,26(10):2199-2214.
[16]DAI Y Y,ZHANG H J,ZHANG J P,et al.Isoquercetin attenuates oxidative stress and neuronal apoptosis after ischemia/reperfusion injury via Nrf2-mediated inhibition of the NOX4/ROS/NF-κB pathway[J].Chem Biol Interact,2018,284:32-40.
[17]LI W,SUWANWELA N C,PATUMRAJ S.Curcumin by down-regulating NF-kB and elevating Nrf2,reduces brain edema and neurological dysfunction after cerebral I/R[J].Microvasc Res,2016,106:117-127.
[18]WANG X,QIN Z H,SHI H,et al.Protective effect of Ginkgolids(A+B)is associated with inhibition of NIK/IKK/IkappaB/NF-kappaB signaling pathway in a rat model of permanent focal cerebral ischemia[J].Brain Res,2008,1234:8-15.