丹参酮IIA改善脓毒症大鼠脑组织损伤和凋亡的作用(南眾甲•区福州总医院350025)【摘要】目的:探讨丹参酮IIA改善脓毒症大鼠脑组织损伤和细胞凋亡的作用及可能的机制。方法:采用盲肠结扎穿孔术制备脓毒症大鼠模型(CLP),给予丹参酮IIA(TanllA)腹腔注射处理。分析治疗6-24h后脑组织TNF-α、IL-lβ、MDA、SOD的水平、病理学变化、细胞凋亡率、促凋亡基因(Bax、Fas、P53和Caspase-3)和抑制凋亡基因(Bcl-2)的表达情况。结果:①脓毒症大鼠中TNF-α和IL-lβ水平显著升高(P<0.05),而丹参酮IIA可以抑制脓毒症大鼠脑组织中TNF-α和IL-lβ水平的升高(P<0.05);②脓毒症大鼠中MDA水平明显升高(P<0.05),SOD水平显著降低(P<0.05);丹参酮IIA干预后,MDA和SOD的异常水平显著改善(P<0.05);③脓毒症组大鼠造模后6h脑组织己出现病理学的异常改变,细胞凋亡指数显著高于假手术组(P<0.05);给予TanIIA处理之后,病理学的异常改变得到明显的改善,凋亡指数显著降低(P<0.05)④Bcl-2的蛋白和mRNA表达水平下降(P<0.05);P53、Bax、Fas和Caspases-3蛋白和mRNA表达水平升高(P<0.05);丹参酮IIA干预可以使上述蛋白和mRNA的异常表达水平部分恢复(P<0.05)o结论:丹参酮IIA具有改善脓毒症大鼠脑组织损伤和细胞凋亡的作用,可能机制是通过其抗炎(TNF-α、IL-lβ)、抗氧化(MDA、SOD)的作用,并调控凋亡相关基因(Bcl-2、Bax、p53、Fas、Caspase-3)的表达来实现。【关键词】丹参酮IIA;脓毒症;作用【中图分类号】R-332【文献标识码】A【文章编号】【Abstract】Objective:ToinvestigatetheeffectoftanshinoneIIAimprovetissueinjuryandapoptosisandthepossiblemechanismsofbraininratswithsepsis.Methods:Theratcecalligationandpuncturesepsismodelpreparationtechnique(CLP),giveTanIIA(Tan11A)byintraperitonealinjectionprocess.Analysisofbraintissuetreatment6-24hTNF-,IL-1,MDA,SODlevels,pathologicalchanges,apoptosisrate,pro-apoptoticgenes(Bax,Fas,P53andCaspase-3)andinhibitionofapoptosisgene(Bcl-2)expression.Results:®sepsisratTNF-αandIL-lβlevelsweresignificantlyincreased(P<0.05),whileTanIIAcaninhibittheincreaseofbraintissueinratswithsepsisTNF-αandIL-lβlevels(P<0.05);②septicratsMDAlevelsweresignificantlyincreased(P<0.05),SODlevelsweresignificantlylower(P<0.05);afterTanIIAintervention,MDAandabnormallevelsofSODsignificantlyimproved(P<0.05);ratbraintissueaftermodeling6h③sepsisgrouphasappearedabnormalpathology,apoptosiswassignificantlyhigherthantheshamgroup(P<0.05);aftertreatmenttogiveTanIIA,pathologicalabnormalitieschangehasbeensignificantlyimproved,theapoptoticindexwassignificantlylower(P<0.05)proteinandmRNAexpressionlevelsof④Bcl-2decreased(P<0.05);increasedP53,Bax,FasandCaspases-3proteinandmRNAexpressionlevels(P<0.05);tanshinoneIIAinterventionscanmaketheabove-mentionedabnormalproteinandmRNAexpressionlevelsofpartialrecovery(P<0.05).Conclusion:TanshinoneIIAhasimprovedcerebraltissuedamageandapoptosisinsepticrats,thepossiblemechanismisthroughitsanti-inflammatory(TNF-α,IL-lβ),antioxidant(MDA,SOD}theroleandregulationapoptosis-relatedgenes(Bcl-2,Baxp53FasCaspase-3,)toachieveexpression.【Keywords】tanshinoneIIA;sepsis;theroleof材料与方法1动物、药物及试剂SPF级雄性SpragueDawley大鼠54只,体重为280g~300g(由北京维通利华实验动物技术奋限公司提供),丹参酮IIA磺酸钠注射液(诺新康;2ml:10mg;上海第一生化药业有限公司,国药准字H31022558),超氧化物歧化酶(SOD)、丙二醛(MDA)以及TNF-α和IL-lβElisa试剂盒购自武汉博士德生物工程有限公司,TUNEL细胞凋亡检测试剂盒购自北京宝塞生物技术有限公司。蛋白抗体购于CellSignalingTechnolgy公司。PCR引物由北京赛百盛基因技术有限公司合成;其余试剂为国产分析纯(武汉...