中华神经科杂志
中華神經科雜誌
중화신경과잡지
Chinese Journal of Neurology
2010年
3期
216-221
,共6页
孙莉%徐艳炜%梁浩%孙国敏%程焱
孫莉%徐豔煒%樑浩%孫國敏%程焱
손리%서염위%량호%손국민%정염
脑缺血%再灌注损伤%PPARα%PPARβ%PPARδ%PPARγ
腦缺血%再灌註損傷%PPARα%PPARβ%PPARδ%PPARγ
뇌결혈%재관주손상%PPARα%PPARβ%PPARδ%PPARγ
Brain ischemia%Reperfusion injury%PPAR alpha%PPAR beta%PPAR delta%PPAR gamma
目的 观察局灶性脑缺血再灌注大鼠过氧化物酶体增殖物激活受体(peroxisome proliferator-activated receptor,PPAR)各亚型(PPARα、PPARδ/β和PPARγ)表达的改变,并初步探讨PPAR改变的意义.方法 健康雄性SD大鼠分为假手术组、模型组、治疗组.制作大鼠大脑中动脉阻塞2 h再灌注22 h模型(MCAO/R),治疗组于MCAO/R前1 h给予PPAR全激动剂苯扎贝特.分别采用3%氯化三苯四唑(2,3,5-triphenyhetrazolium,TTC)染色法观察脑梗死体积;Western blot法和免疫组织化学法观察PPAR各亚型蛋白表达和分布的变化.结果 与假手术组相比,脑缺血再灌注(1)引起梗死的平均体积为44.30%;(2)使脑组织PPAR各亚型表达均增加,分别增加了1.47、3.52和2.25倍,差别具有统计学意义(免疫组织化学检测t值分别为8.63、9.29和13.62,Western blot检测t值分别为8.16、9.24和6.43,均P=0.000);(3)PPAR各亚型免疫阳性细胞增加主要表现在缺血侧半暗带区域,而非缺血侧(对侧)表达没有明显改变.与模型组相比,苯扎贝特能够:(1)显著降低脑梗死体积,平均减少54.36%,差异具有统计学意义(t=7.69,P=0.000);(2)进一步增加PPAR各亚型表达,分别增加了95.45%、183.47%、224.61%,差异具有统计学意义(免疫组织化学检测t值分别为7.36、5.64和10.50,Western blot检测t值分别为13.02、17.52和13.64,均P=0.000);(3)不但使缺血侧PPAR免疫阳性细胞增加,而且使非缺血侧增加.结论 局灶性脑缺血再灌注损伤大鼠脑组织PPARα、PPARδ/β和PPARγ表达增加,可能是脑组织的一种代偿性神经保护反应.
目的 觀察跼竈性腦缺血再灌註大鼠過氧化物酶體增殖物激活受體(peroxisome proliferator-activated receptor,PPAR)各亞型(PPARα、PPARδ/β和PPARγ)錶達的改變,併初步探討PPAR改變的意義.方法 健康雄性SD大鼠分為假手術組、模型組、治療組.製作大鼠大腦中動脈阻塞2 h再灌註22 h模型(MCAO/R),治療組于MCAO/R前1 h給予PPAR全激動劑苯扎貝特.分彆採用3%氯化三苯四唑(2,3,5-triphenyhetrazolium,TTC)染色法觀察腦梗死體積;Western blot法和免疫組織化學法觀察PPAR各亞型蛋白錶達和分佈的變化.結果 與假手術組相比,腦缺血再灌註(1)引起梗死的平均體積為44.30%;(2)使腦組織PPAR各亞型錶達均增加,分彆增加瞭1.47、3.52和2.25倍,差彆具有統計學意義(免疫組織化學檢測t值分彆為8.63、9.29和13.62,Western blot檢測t值分彆為8.16、9.24和6.43,均P=0.000);(3)PPAR各亞型免疫暘性細胞增加主要錶現在缺血側半暗帶區域,而非缺血側(對側)錶達沒有明顯改變.與模型組相比,苯扎貝特能夠:(1)顯著降低腦梗死體積,平均減少54.36%,差異具有統計學意義(t=7.69,P=0.000);(2)進一步增加PPAR各亞型錶達,分彆增加瞭95.45%、183.47%、224.61%,差異具有統計學意義(免疫組織化學檢測t值分彆為7.36、5.64和10.50,Western blot檢測t值分彆為13.02、17.52和13.64,均P=0.000);(3)不但使缺血側PPAR免疫暘性細胞增加,而且使非缺血側增加.結論 跼竈性腦缺血再灌註損傷大鼠腦組織PPARα、PPARδ/β和PPARγ錶達增加,可能是腦組織的一種代償性神經保護反應.
목적 관찰국조성뇌결혈재관주대서과양화물매체증식물격활수체(peroxisome proliferator-activated receptor,PPAR)각아형(PPARα、PPARδ/β화PPARγ)표체적개변,병초보탐토PPAR개변적의의.방법 건강웅성SD대서분위가수술조、모형조、치료조.제작대서대뇌중동맥조새2 h재관주22 h모형(MCAO/R),치료조우MCAO/R전1 h급여PPAR전격동제분찰패특.분별채용3%록화삼분사서(2,3,5-triphenyhetrazolium,TTC)염색법관찰뇌경사체적;Western blot법화면역조직화학법관찰PPAR각아형단백표체화분포적변화.결과 여가수술조상비,뇌결혈재관주(1)인기경사적평균체적위44.30%;(2)사뇌조직PPAR각아형표체균증가,분별증가료1.47、3.52화2.25배,차별구유통계학의의(면역조직화학검측t치분별위8.63、9.29화13.62,Western blot검측t치분별위8.16、9.24화6.43,균P=0.000);(3)PPAR각아형면역양성세포증가주요표현재결혈측반암대구역,이비결혈측(대측)표체몰유명현개변.여모형조상비,분찰패특능구:(1)현저강저뇌경사체적,평균감소54.36%,차이구유통계학의의(t=7.69,P=0.000);(2)진일보증가PPAR각아형표체,분별증가료95.45%、183.47%、224.61%,차이구유통계학의의(면역조직화학검측t치분별위7.36、5.64화10.50,Western blot검측t치분별위13.02、17.52화13.64,균P=0.000);(3)불단사결혈측PPAR면역양성세포증가,이차사비결혈측증가.결론 국조성뇌결혈재관주손상대서뇌조직PPARα、PPARδ/β화PPARγ표체증가,가능시뇌조직적일충대상성신경보호반응.
Objective To examine peroxisome proliferator-activated receptor(PPAR)isotypes (PPARα,PPARδ/βand PPARγ)expression in rats after cerebral ischemia-reperfusion(I/R)and I/R in combination with pan-PPAR co-agonist,and to explore the effect of altered PPAR expressions in brain injury.Methods Adult male SD rats underwent 2-hour middle cerebral artery occlusion followed by a 22-hour reperfusion(MCAO/R).One hour before the operation,the mice received either vehicle(I/R-group)or bezafibrate(6 mg/kg)treatment(Beza-group).TTC(2,3,5-triphenyhetrazolium)staining was adopted to determine the volume of cerebral infarction.The expressions of PPAR isotypes were characterized by immunohistochemical staining(IHC)and Western blot.Furthermore,the spatial localizations of PPAR isotypes were analyzed with respect to ipsilateral ischemic(core and penumbra)and contralateral nonischemic hemisphere.Results Compared with sham-group,2 h ischemia and 22 h reperfusion caused(1) 44.30%infarct volume in average in ipsilateral hemisphere;(2)Marked increased PPAR expression in all three isotypes evaluated by IHC(t=8.63,9.29,13.62,P:0.000)and Western blot(PPARot by 1.47-fold,PPARδ/β by 3.52-fold,and PPARγ by 2.25-fold;t=8.16,9.24,6.43;P=0.000);(3)Marked increagc in PPAR staining in the ischemia-affected region of the ipsilateral MCA territory,in particular in the ischemic itmnumbra.No detectable increase in number and intensity was observed in the contralateral(nonischemic)hemisphere.The pan-PPAR co-agonists bezafibrate can activate all 3 subtypes of the receptor.Compared with I/R-group,(1)Ischemic size in bezafibrate-group rats was significantly decreased than that in I/R group(20.22±6.18 versus 44.30±4.54,t=7.69,P=0.000).(2)Bezafibrate treatment further increased the alterations of all PPAR expression,which were induced by the exposure of I/R,as determined by IHC(t=7.36,5.64,10.50,and P=0.000)and Western blot(PPARα by 95.45%,PPARS/β by 183.47%,and PPARγ by 224.61%;t=13.02,17.52,13.64,and P=0.000).(3)The PPAR immunoreactive expressions were observed in not only the ipsilateral but the contralateral hemisphere of bezafibrate-group.Conclusions Cerebral I/R injury increases the expression of all three PPAR isotypes and activation of PPAR by pan-PPAR agonist not only reduces ischemic size but further enhances the alteration of PPAR The up-regulation of PPAR expression may represent the compensatory self-protection against brain I/R injury.
