Neuregulin通過(guò)CD98hc激活MAPK信號(hào)通路對(duì)人臍靜脈內(nèi)皮細(xì)胞的保護(hù)作用.pdf

1、齊翔：Neuregulin通過(guò)CD98hc激活MAPK信號(hào)通路對(duì)人臍靜脈內(nèi)皮細(xì)胞的保護(hù)作用1Neuregulin通過(guò)CD98hc激活MAPK信號(hào)通路對(duì)人臍靜脈內(nèi)皮細(xì)胞的保護(hù)作用中文摘要第一部分高濃度葡萄糖誘導(dǎo)人臍靜脈內(nèi)皮細(xì)胞(HUVEC)凋亡的作用目的：觀察高濃度葡萄糖誘導(dǎo)人臍靜脈內(nèi)皮細(xì)胞(HUVEC)凋亡的作用。方法：將人臍靜脈內(nèi)皮細(xì)胞用25mmol／L葡萄糖DMEM培養(yǎng)基(陰性對(duì)照組)、50mmol／L葡萄糖DMEM培養(yǎng)基、75mm

2、ol／L葡萄糖DMEM培養(yǎng)基、100mmol／L葡萄糖DMEM培養(yǎng)基、75mmol／L甘露醇25mmol／L葡萄糖DMEM培養(yǎng)基(陽(yáng)性對(duì)照組)培養(yǎng)48h，觀察不同分組人臍靜脈內(nèi)皮細(xì)胞形態(tài)并測(cè)定各組細(xì)胞活力(WST8)，測(cè)定各組細(xì)胞凋亡情況，及分析CD98hc、p38、JNK蛋白的表達(dá)情況。結(jié)果：不同濃度葡萄糖培養(yǎng)環(huán)境下的人臍靜脈內(nèi)皮細(xì)胞形態(tài)存在明顯差異。在一定的葡萄糖濃度范圍內(nèi)，人臍靜脈內(nèi)皮細(xì)胞凋亡程度與培養(yǎng)基中葡萄糖濃度呈正相關(guān)；CD

3、98hc蛋白表達(dá)與培養(yǎng)基中葡萄糖濃度呈負(fù)相關(guān)；JNK蛋白表達(dá)與培養(yǎng)基中葡萄糖濃度呈負(fù)性相關(guān)；p38蛋白表達(dá)與培養(yǎng)基中葡萄糖濃度無(wú)明顯關(guān)系。結(jié)論：在人臍靜脈內(nèi)皮細(xì)胞凋亡過(guò)程中，CD98hc蛋白表達(dá)降低，p38蛋白表達(dá)無(wú)明顯差異，JNK表達(dá)明顯降低。這些結(jié)果說(shuō)明，高濃度葡萄糖可能是通過(guò)阻斷MAPK信號(hào)通路中JNK亞族，使HUVEC生長(zhǎng)被抑制，引起HUVEC凋亡。第二部分Neuregulin通過(guò)CD98he激活MAPK信號(hào)通路對(duì)人臍靜脈內(nèi)皮細(xì)

4、胞的保護(hù)作用目的：觀察Neuregulin對(duì)人臍靜脈內(nèi)皮細(xì)胞的保護(hù)作用。方法：將人臍靜脈內(nèi)皮細(xì)胞用25mmol／L葡萄糖DMEM培養(yǎng)基10ng／ml、100ng／ml、1000ng／mlneuregulin(陰性對(duì)照組)，75mmol／L葡萄糖DMEM培養(yǎng)基10ng／ml、lOOng／ml、1000ng／mlneuregulin，75mmol／L甘露醇25mmol／L葡萄糖DMEM培養(yǎng)基lOng／ml、100ng／ml、1000ng／m

5、lneuregulin(陽(yáng)性對(duì)照組)培養(yǎng)48h，觀察不同分組人臍靜脈內(nèi)皮細(xì)胞形態(tài)，測(cè)定各組細(xì)胞凋亡情況，分析CD98he、p38、JNK蛋白的表達(dá)情況。齊翔：Neuregulin通過(guò)CD98hc激活MAPK信號(hào)通路對(duì)人臍靜脈內(nèi)皮細(xì)胞的保護(hù)作用3Neuregulinprotectshumanumbilicalveinendothelialcell(HUVEC)viaactivatingCD98hcthroughMAPKpathwayAbs

6、tractPartIApoptosiseffectsofhighglucoseonHUVECobieetives：observetheapoptosiseffectsofhighglucoseonHUVECMethods：HUVECwereculturedwitll25mmol／LglucoseDMEMmediumfnegativecontr01)，50mmol／LglucoseDMEMmedium，75mmol／LglucoseDME

7、Mmedium，100mmol|LglucoseDMEMmediBinand75retool|Lmaunito、＼25mmol|LglucoseDMEMmedium(positivecontr01)for48h，themorphologicalchangesofcellswereobservedunderthemicroscopeandtheeellviability(MTTlWaSdetectedApoptosiswasmeasure

8、dineachgroupandtheexpressionofproteinofCD98hc，p38，ⅢKwasanalyzedResults：ThemorphologydifferencesofmrVECculturedindifferentconcentrationsofglucoseweresignificantThecorrelationofHUVECapoptosisandglucoseconcentrationwasposit

9、ivelyThecorrelationofexpressionofCD98heandglucoseconcentrationwasnegativelyThecorrelationof胍andglucoseconcentrationwaspositivelyThereWaSnosignificantcorrelationbetweenexpressionofp38andglucoseconcentrationConclusions：The

10、expressionofproteinCD98hcreduceinHUVECapoptosisprocessandthereisnosignificantdifferenceofexpressionofproteinp38theexpressionof胍WaSsignificantlyincreaSedTheseresultssuggestthathighglucosemaycauseHUVECapoptosisviaactivate胍

11、subtribeofMAPKpathwayKeywords：HUVEC；highglucose；apoptosis；Neuregulin；M漁PKpathwayPartIIProtectiveeffectsofneuregulinonHUVECobiectives：ObservetheprotectiveeffectsofneuregnlinonHUVECMethods：HUVECwereculturedwith25retool／Lgl

12、ucoseDMEMmediumlOng／m11OOng／mlandl000ng／mlneuregulin(negativecontr01)。75mmol|LglucoseDMEMmediunl10ng／m11OOng／mland1000ng／mlneuregulinand75mmol／Lmannitol25nllnOl／LglucoseDMEMmedium10ng／ml，lOOng／mlandl000ng／mlneuregulin(po

13、sitivecontr01)for48hthemorphologicalchangesofcellswereobservedundert11emicroscopeApoptosiswasmeasuredineachgroupandtheexpressionofproteinofCD98hc，p38。腫【W(wǎng)aSanalyzedResults：Comparedwiththecontrolgroupthemorphologydifferenc

14、esofHUVECculturedindifferentconcentrationsofneuregulinweresignificantIntheexperimentalgroupthecorrelationofHUVECapoptosisandneuregulinconcentrationwasnegativelyThecorrelationofexpressionofCD98hcandneuregulinconcentration