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ID:34719857
大小:7.11 MB
页数:51页
时间:2019-03-10
《腺病毒介导的il-10及igf-1基因联合干预对nod鼠t1dm发病早期胰岛β细胞的保护作用》由会员上传分享,免费在线阅读,更多相关内容在学术论文-天天文库。
1、腺病毒介导的鼠lL-10及lGF-1基因联合干预对NOD鼠T1嗍发病早期胰岛13细胞的保护作用摘要目的观察腺病毒介导的鼠白细胞介素i0(Ad-mIL-lO)及胰岛素样生长因子l(Ad-mIGF-1)基因联合干预对NOD小鼠1型糖尿病发病早期胰岛13细胞的保护作用,为临床早期干预提供动物实验基础。方法17-20周龄近期发病的雌性NOD小鼠24只,随机分为OAd-mlGF一1组、②Ad-mIL-10组、@)Ad-mIL-IO+Ad-mIGF-1组、④糖尿病对照组,另选取相同周龄、至实验末仍未发病的小鼠为⑤空白对照组。发病后立即干预,分别给予①、②、③组腹腔注射Ad—mIGF-1、A
2、d-mlL-lO、Ad-mIL-IO+Ad-mIGF-1,各0.Iml,④、⑤组未予任何干预。定期监测小鼠体质量、尿糖及血糖,行胰腺病理切片HE染色及免疫组化观察胰岛炎症浸润程度和IL一10、IGF-1基因胰腺表达情况,测定血清IL00、IGF~l、IFN_Y、IL一4和C肽水平。结果1.IL-IO、IGF-1基因在胰腺局部表达增强,血清中水平也相应升高;2.基因干预后小鼠血清IFN-Y水平降低,IL一4、IL-10水平升高,联合基因干预组效果更显著(p<0.01);IL-IO单基因干预组较IGF-1单基因干预组IFN-y水平降低,IFN—Y/IL_4降低(p3、IL-IO单基因及联合基因干预后C肽水平升高,联合基因干预组升高更明显(p<0.01),但IGF一1单基因干预组C肽水平未升高(p>0.05);4.与糖尿病对照组小鼠比较,基因干预组小鼠胰岛炎程度及血糖水平差异无统计学意义(p>O.05),在基因干预后3周时IL-lO单基因及联合基因干预组小鼠体质量降低(p4、更显著;3.IL-IO单基因及联合基因干预,可发挥一定地胰岛13细胞功能保护作用,其中联合基因干预效果更明显,但IGF一1单基因干预组未发现此作用;lllttll4IIIIUfulfil41IElldIIIIIItlIY23387494.IL一10和/IGF一1基因干预,无减轻胰岛炎作用,在控制血糖水平及增加体质量方面无改善作用。硕士研究生:陈燕燕(儿科学)指导教师:李堂教授关键词:白细胞介素10;胰岛素样生长因子1;胰岛B细胞;NOD小鼠;1型糖尿病ProtectiveEffectofCombinedInterventionwithAdenovirusVectorMediat5、edIL-IOandIGF.1GeneonEndogenousIsletpCellsinNew.onsetT1DMofNODmiceAbstractObjectiveToinvestigatetheprotectiveeffectofcombinedinterventionwithadenovirusvectormediatedIL.10andIGF。1geneonisletpcellsattheearlystageoftype1diabetesmellitusinNODmice,inordertoprovideanimalexperimentalbasisfortheearl6、yclinicalintervention.MethodsTwenty.fourfemaleNODmiceagedfromseventeentotwentyweekswererandomlyandaveragelydividedintofourgroups:OAd—mlGF-1group、②Ad-mlL_10group、③Ad.mIGF.1andAd.mlL.10combinedgroupand@diabetescontrolgroup,andthesemicewouldbedignosedasrecent—onsetofT1DM.Theothersixmiceofthesam7、eaged,withouttheavdentofdiabetesuntilltheendofexperiment,wereselectedinthe⑤salinecontrolgroup.Aftertheonsetofdiabetes,①、②and③groupwerereceivedintrape!ritonealinjecfionofAd—mI(弭.1、Ad.raiL一10andAd·mlGF·1+Ad—mlL-10atthedoseofO.1ml,respectively.(4鸯and⑤
3、IL-IO单基因及联合基因干预后C肽水平升高,联合基因干预组升高更明显(p<0.01),但IGF一1单基因干预组C肽水平未升高(p>0.05);4.与糖尿病对照组小鼠比较,基因干预组小鼠胰岛炎程度及血糖水平差异无统计学意义(p>O.05),在基因干预后3周时IL-lO单基因及联合基因干预组小鼠体质量降低(p4、更显著;3.IL-IO单基因及联合基因干预,可发挥一定地胰岛13细胞功能保护作用,其中联合基因干预效果更明显,但IGF一1单基因干预组未发现此作用;lllttll4IIIIUfulfil41IElldIIIIIItlIY23387494.IL一10和/IGF一1基因干预,无减轻胰岛炎作用,在控制血糖水平及增加体质量方面无改善作用。硕士研究生:陈燕燕(儿科学)指导教师:李堂教授关键词:白细胞介素10;胰岛素样生长因子1;胰岛B细胞;NOD小鼠;1型糖尿病ProtectiveEffectofCombinedInterventionwithAdenovirusVectorMediat5、edIL-IOandIGF.1GeneonEndogenousIsletpCellsinNew.onsetT1DMofNODmiceAbstractObjectiveToinvestigatetheprotectiveeffectofcombinedinterventionwithadenovirusvectormediatedIL.10andIGF。1geneonisletpcellsattheearlystageoftype1diabetesmellitusinNODmice,inordertoprovideanimalexperimentalbasisfortheearl6、yclinicalintervention.MethodsTwenty.fourfemaleNODmiceagedfromseventeentotwentyweekswererandomlyandaveragelydividedintofourgroups:OAd—mlGF-1group、②Ad-mlL_10group、③Ad.mIGF.1andAd.mlL.10combinedgroupand@diabetescontrolgroup,andthesemicewouldbedignosedasrecent—onsetofT1DM.Theothersixmiceofthesam7、eaged,withouttheavdentofdiabetesuntilltheendofexperiment,wereselectedinthe⑤salinecontrolgroup.Aftertheonsetofdiabetes,①、②and③groupwerereceivedintrape!ritonealinjecfionofAd—mI(弭.1、Ad.raiL一10andAd·mlGF·1+Ad—mlL-10atthedoseofO.1ml,respectively.(4鸯and⑤
4、更显著;3.IL-IO单基因及联合基因干预,可发挥一定地胰岛13细胞功能保护作用,其中联合基因干预效果更明显,但IGF一1单基因干预组未发现此作用;lllttll4IIIIUfulfil41IElldIIIIIItlIY23387494.IL一10和/IGF一1基因干预,无减轻胰岛炎作用,在控制血糖水平及增加体质量方面无改善作用。硕士研究生:陈燕燕(儿科学)指导教师:李堂教授关键词:白细胞介素10;胰岛素样生长因子1;胰岛B细胞;NOD小鼠;1型糖尿病ProtectiveEffectofCombinedInterventionwithAdenovirusVectorMediat
5、edIL-IOandIGF.1GeneonEndogenousIsletpCellsinNew.onsetT1DMofNODmiceAbstractObjectiveToinvestigatetheprotectiveeffectofcombinedinterventionwithadenovirusvectormediatedIL.10andIGF。1geneonisletpcellsattheearlystageoftype1diabetesmellitusinNODmice,inordertoprovideanimalexperimentalbasisfortheearl
6、yclinicalintervention.MethodsTwenty.fourfemaleNODmiceagedfromseventeentotwentyweekswererandomlyandaveragelydividedintofourgroups:OAd—mlGF-1group、②Ad-mlL_10group、③Ad.mIGF.1andAd.mlL.10combinedgroupand@diabetescontrolgroup,andthesemicewouldbedignosedasrecent—onsetofT1DM.Theothersixmiceofthesam
7、eaged,withouttheavdentofdiabetesuntilltheendofexperiment,wereselectedinthe⑤salinecontrolgroup.Aftertheonsetofdiabetes,①、②and③groupwerereceivedintrape!ritonealinjecfionofAd—mI(弭.1、Ad.raiL一10andAd·mlGF·1+Ad—mlL-10atthedoseofO.1ml,respectively.(4鸯and⑤
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