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《35丁基苯酞抗大鼠大腦皮質(zhì)神經(jīng)元氧糖剝奪_復(fù)氧損傷及其機制08.4.12》由會員上傳分享，免費在線閱讀，更多相關(guān)內(nèi)容在教育資源-天天文庫。
1、·366·藥學(xué)學(xué)報ActaPharmaceuticaSinica2008,43(4):366-370丁基苯酞抗大鼠大腦皮質(zhì)神經(jīng)元氧糖剝奪/復(fù)氧損傷及其機制3吳麗蓉,羅勇(重慶醫(yī)科大學(xué)附屬第一醫(yī)院,重慶市神經(jīng)病學(xué)重點實驗室,重慶400016)摘要:本研究探討丁基苯酞抗大鼠大腦皮質(zhì)神經(jīng)元氧糖剝奪/復(fù)氧損傷及其機制。原代培養(yǎng)大鼠大腦皮質(zhì)神經(jīng)元,建立氧糖剝奪/復(fù)氧模型(OGD/R),采用MTT法、酶學(xué)檢查、免疫組化、RT2PCR等觀察丁基苯酞(各濃度組)的保護作用及其機制。在氧糖剝奪4h/復(fù)氧8h時丁基苯酞各濃度組可增加神經(jīng)元的細
2、胞活力和減少神經(jīng)元LDH(乳酸脫氫酶)的釋放,可顯著降低神經(jīng)元表達iNOSmRNA(誘生型一氧化氮合酶)和NF2κB(核因子κB)p65蛋白(增-1加)。不同劑量丁基苯酞(100、10、1和011μmol·L)在增加細胞活力、減少LDH釋放及降低神經(jīng)元表達iNOS-1mRNA等方面,高濃度的作用強于低濃度,且丁基苯酞100μmol·L組與吡咯烷二硫代氨基甲酸酯(pyrrolidine-1dithiocarbamate,PDTC)100μmol·L組差異顯著。在OGD4h/R8h時丁基苯酞可能抑制iNOSmRNA的表達及NF
3、2κB的活化,從而有效保護氧糖剝奪/復(fù)氧中損傷的大腦皮質(zhì)神經(jīng)元。關(guān)鍵詞:丁基苯酞;核因子κB;氧糖剝奪/復(fù)氧;大腦皮質(zhì)神經(jīng)元;誘生型一氧化氮合酶中圖分類號:R963文獻標(biāo)識碼:A文章編號:0513-4870(2008)04-0366-05Mechanismofactionofbutylphalideagainsttheinjuryfollowingoxygenglucosedeprivation/reoxygenationinratcorticalneurons3WULi2rong,LUOYong(TheFirstAffi
4、liatedHospital,ChongqingMedicalUniversity,KeyLabofNeurologyinChongqing,Chongqing400016,China)Abstract:Toexplorethemechanismofactionofbutylphalide(NBP)againsttheinjuryfollowingoxygenglucosedeprivation/reoxygenation(OGD/R)inratcorticalneurons,neuronsofWistarnewbornr
5、atswerepreparedbyfilteringthroughamesh,centrifugationandtrypsogendigestion.Asimple,stableandreliableinvitromodelofOGD/Rofneuronswasestablished.Westudiedtheactivation,thenucleartranslocationofNF2κBp65andthemRNAexpressionofiNOSaffectedbyNBPineachgroupneuronbyRT2PCR.
6、NBPisprovedtobeabletoaddcellularvigoranddecreaseLDHrelease.ThemRNAexpressionofiNOSinneuronsafterOGD4h/R8hdecreasedwhentreatedwithNBP.ThereisstatisticaldifferencebetweeneachconcentrationofNBPthatitaddscellularvigor,decreasesLDHreleaseandexpressionof-1iNOSinneuronsa
7、fterOGD4h/R8h.ThereisalsostatisticaldifferencebetweenNBP(100μmol·L)-1andPDTC(100μmol·L).ItisprovedthatNBPcanprotectneurons,blockupregulationofiNOSmRNA,andrestrainactivationofNF2κBinneurons.Keywords:NBP;NF2κB;oxygenglucosedeprivation/reoxygenation;corticalneurons;i
8、NOS丁基苯酞(NBP)是從我國南方的一種水芹籽中重建缺血區(qū)微循環(huán),縮小腦梗塞面積,保護線粒體,提取出來的有效成分,可分為左旋丁基苯酞改善腦缺血后能量代謝,減輕局部腦缺血所致的腦[1～5](l2NBP)、右旋丁基苯酞(d2NBP)及消旋丁基苯酞水腫等。既往的研究主要著眼于丁基苯酞對低(dl2NBP),其
