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1、雷公藤在大鼠1型糖尿病模型中对调节性T细胞Foxp3表达的影响及意义【摘要】 目的:研究雷公藤在大鼠1型糖尿病模型中对CD4+CD25+调节性T细胞(Tr)Foxp3基因表达的影响及意义。方法:将48只大鼠随机分为3组,每组各16只,Ⅱ、Ⅲ组采用小剂量多次腹腔注射链脲佐菌素(STZ)的方法制备大鼠1型糖尿病模型,Ⅰ组为正常对照。Ⅲ组在成模后给与雷公藤多甙(GTT)灌胃,1次/d,连续3个月。淋巴细胞转化试验(MTT法)检测脾淋巴细胞增殖活性;荧光定量PCR检测外周血及脾淋巴细胞Foxp3mRNA的表达;免疫组化检测淋巴结和
2、脾组织FOXP3蛋白的表达。结果:Ⅱ、Ⅲ组血糖水平高于Ⅰ组(P<0.01);胰岛中Ⅲ组淋巴细胞浸润程度较Ⅱ组减轻;Ⅱ、Ⅲ组淋巴细胞增殖活性均较Ⅰ组升高(P<0.01),用药后Ⅲ组较Ⅱ组降低;Foxp3mRNA、FOXP3蛋白表达水平Ⅱ、Ⅲ组均高于Ⅰ组(P<0.05),Ⅲ组表达水平较Ⅱ组有所升高,但差别无统计学意义(P>0.05)。结论:Foxp3+Tr细胞参与了STZ诱导的大鼠1型糖尿病的发生发展;上调Tr细胞Foxp3基因的表达可能为雷公藤治疗1型糖尿病的机制之一。【关键词】CD4+CD25+调节性
3、T细胞Foxp3雷公藤1型糖尿病 [Abstract]AIM:ToinvestigatethesignificanceandeffectofGlucosidorumTripterygiitororum(GTT)onthe13expressionsofFoxp3inCD4+CD25+regulatoryTcells(Tr)intype1diabeticratmodel.METHODS:48ratsweredividedevenlyinto3groupsbyrandom.Diabeticmodelwasdevelopedbym
4、ultiplelowdoseintraperitonealinjectionofstreptozotociningroupⅡ,Ⅲ,andgroupⅠwastreatedasnormalcontrol.Aftertheestablishmentofthemodel,administrationofGTTwasconductedingroupⅢ,whichwasperformedonceaday,lastingthreemonthes.Lymphocyteproliferationwasdetectedbylymphocytet
5、ransformationtest(MTTassay).TheexpressionofFoxp3mRNAwasmeasuredinperipheralbloodandspleenbyusingrealtimePCR.TheexpressionofFoxp3proteininlymphoidnodeandspleenwasdetectedbyimmunohistochemistry.RESULTS:ThebloodglucoselevelingroupⅡ,Ⅲwasobviouslyhigherthanthatofcontro
6、lgroup(P<0.01),followedwithlymphocyteinfiltratinginpancreaticislets.TheinfiltratingdegreeingroupⅢwasdecreasedthanthatofgroupⅡ.TheproliferationofspleniclymphocyteingroupⅡ,Ⅲwasevidentlyincreasedcomparingwiththecontrolgroup(P<0.01).AfteradministrationofGTT,thepr
7、oliferationingroupⅢwaslowerthanthatingroupⅡ.IngroupⅡ,Ⅲ,theexpressionsofFoxp3mRNAandproteinincreasedmarkedlycomparedwithcontrolgroup(P<0.05).Moreover,thelevelingroupⅢwasespecially13enhanced,butcomparedwithgroupⅡ,therewasnosignificantlydifference(P>0.05).CONCLU
8、SION:Foxp3+Trmayinvolveinthepathogenesyoftype1diabetesindusedbySTZ.GTTdidhavetherapeuticaleffectontype1diabetes,possiblythroughupregulatingtheexp