阿托伐他汀对大鼠再狭窄血管醛糖还原酶表达及内膜增生的抑制作用VIP专享VIP免费

CN43．1262／R中国动脉硬化杂志2006年第14卷第6期487[文章编号]1007．3949(2006)14-06-0487．04阿托伐他汀对大鼠再狭窄血管醛糖还原酶表达及内膜增生的抑制作用·实验研究·郑春华。周胜华。刘启明。李旭平。沈向前。曹德良。万腊香(1．南昌市第一医院心内科，江西省南昌市330008；2．中南大学湘雅二医院心导管室，湖南省长沙市410011；3．南华大学心血管病研究所，湖南省衡阳市421001)【关键词]内科学；阿托伐他汀对醛糖还原酶表达及内膜增生的抑制作用；FISH原位杂交；阿托伐他汀；醛糖还原酶；内膜增生；再狭窄【摘要]目的研究醛糖还原酶在大鼠再狭窄血管中的表达，探讨醛糖还原酶表达与内膜增生之间的关系，以及阿托伐他汀对醛糖还原酶表达及内膜增生的抑制作用。方法24只健康雄性SD大鼠，随机分成手术未干预组、假手术组及阿托伐他汀组，每组8只。用通气一干燥法损伤手术未干预组及阿托伐他汀组中的右侧颈总动脉，左侧颈总动脉作为对照。分别于第7天及14天处死动物，HE染色以观察内膜及中膜增生情况，并计算内膜和中膜面积及其比值，兀SH原位杂交及免疫组织化学检测醛糖还原酶及核因子，cB的表达。结果术后第7天损伤侧血管内膜增生明显，第14天内膜增生进一步加重，对照血管无明显增生。阿托伐他汀组血管内膜面积、内膜与中膜面积比值明显低于手术未干预组(P<0．05或P<0．01)。醛糖还原酶及核因子KB在损伤侧血管中的表达明显强于对照侧。阿托伐他汀组醛糖还原酶及核因子KB的表达明显低于手术未干预组(P<0．05或P<0．01)。结论醛糖还原酶可能参与了大鼠颈动脉损伤后内膜增生及再狭窄的形成。阿托伐他汀可抑制血管内膜增生及再狭窄的形成。阿托伐他汀可能是通过抑制醛糖还原酶及核因子．cB而抑制再狭窄的形成。【中图分类号]R5[文献标识码]ATheInhibitionofAtorvastatinonAldoseReductaseExpressionandIntimalHyperplasiaintheIntervention砌tswithRestenosis踟Chun-Hua。ZHOUSheng-Hua~。删Qi—Mid。LIXu-Ping2-S皿NXiang-Qia-CAODe．．HangJ-andwANLa-Xia~(1．D口ofCardiology，theFirstHospitalofNanchang，／~hnchang330008；2、theCatheterD删of如gy，SecondXiangyaHos—pofCentralSouth，c^g410011；3、theAng／ocard／opathyResearch／nst／aaeofNaahuaUnhm'st2y，Hengyang421001；Ch／na)【KEYWORDS]Atorvastafin；AldoseReductase；IntimalHyperplasia；Restenosis；NuclearFactor-roB；VascularSmoothMuscleCeU【ABSTRACT]AimTostudytheexpressionofaldosereduetase【AR)inthecarotidsoftheratswithrestenosisinordertoprobeintotherelationshipbetweenARexpressionandintimalhyperplasia，andfurtherexploretheinhibitionofatorvastafinonAIlexpressionandintimalhyperplasia／nthecarotidswithrestenosis．Methods24healthymaleSDratsweredividedintotheinjuriedgroupwithouttreal~nent，thefakeop_eongroupandtheatorvastafingroupbychance．Eachgrouphad8rats．rightcarotidswereinjuriedbyair-drying叩eIationinthetreal~nentgroupandthegroupwithoperationbutwithouttreal~nent．111eleftcarotidswereactedasthecontrols．，I1ratswerekilledafter7daysand14daysrespectively．Dyi,~witIlHEtoexaminetheintimalandthemediallayers’proliferation．Andtheacreageoftheinfimalandthemediallayersandtheirratiowerecalcu一1atedaswel1．Thent|leexpressionofnuclearfactor-xB(KB)andARwereexaminedbyimmunohistochemicalmethodsandFISHinsituhybridization．ResultsSevendaysaftertheinj,~,-y，theintimalhyperplasiacouldbeseenobviouslyintheinju—riedsidesofthecarotids，bytheendof14days-theintimalhyperplasiaaggravated．WlIilethecarotidsinthecontrolsideswerenot．111eacreageoftheintimallayers．theratiooftheintimalandthemediallayersintheatorvastatingroupwasobviouslylowerthanthatoftheoperationgroupwithouttrealTnent．111ediferencewasobviouswhencomparedwitheachother(P<0．05orP<0．01)．111eexpressionofARandNF-KBintheinjuriedsidesw...