中国循环杂志
中國循環雜誌
중국순배잡지
CHINESE CIRCULATION JOURNAL
2014年
8期
624-628
,共5页
韩劲松%王辉山%韩宏光%尹宗涛%汪曾炜
韓勁鬆%王輝山%韓宏光%尹宗濤%汪曾煒
한경송%왕휘산%한굉광%윤종도%왕증위
老年%缺血预适应%缺血再灌注%过氧化物酶体增生激活受体γ协同刺激因子1α
老年%缺血預適應%缺血再灌註%過氧化物酶體增生激活受體γ協同刺激因子1α
노년%결혈예괄응%결혈재관주%과양화물매체증생격활수체γ협동자격인자1α
Aging%Ischemic preconditioning%Ischemia-reperfusion%PGC-1α
目的:本研究探索心肌缺血预适应(IPC)对老年大鼠心肌缺血再灌注(I/R)后的影响及机制。<br> 方法:取21~23月龄老年Wistar大鼠32只,建立离体心脏Langendorff灌注模型,分为4组(每组8只):对照组、I/R组、IPC组、强化IPC组。对照组采用全心灌流180 min,不做任何处理。I/R组采用心脏平衡灌流30 min后,缺血30 min,再复灌120 min。IPC组采用心脏平衡灌流10 min,经两次缺血5 min再灌注5 min后,缺血30 min,再复灌120 min。强化IPC组采用心脏平衡灌流10 min,经四次缺血5 min再灌注5 min后,缺血30 min ,再复灌120 min。比较各组复灌30 min、60 min、90 min、120 min后心排血量的恢复率以及左心室发展压、左心室内压最大上升和下降速率(±dp/dtmax)的恢复率;检测缺血前及复灌120 min后冠状动脉流出液中肌酸激酶MB同工酶(CK-MB)和乳酸脱氢酶活性,心肌组织中丙二醛含量和超氧化物歧化酶的活性。各组取心尖肌做冰冻切片行过氧化物酶体增生激活受体γ协同刺激因子1α(PGC-1α)免疫组织化学染色,计算出平均积分吸光度。<br> 结果:IPC组与I/R组丙二醛含量、CK-MB及超氧化物歧化酶活性,左心室发展压、±dp/dtmax恢复率比较差异无统计学意义(P>0.05),而强化IPC组与I/R组比较,CK-MB和超氧化物歧化酶活性明显减少(P<0.01),丙二醛含量明显降低(P<0.05),超氧化物歧化酶活性明显增加(P<0.01),心排血量、左心室发展压、±dp/dtmax恢复率明显增加(P<0.01),差异有统计学意义。PGC-1α的表达:IPC组与I/R组比较差异无统计学意义(P>0.05),而强化IPC组表达明显增加,与I/R组比较差异有统计学意义(P<0.01)。<br> 结论:老年大鼠心肌IPC的保护作用减弱,可能机制是老年心肌PGC-1α蛋白表达降低,使老年心肌调节超氧化物歧化酶活性的作用下降,进而影响老年心肌对应激反应的防护能力,使IPC对老年心肌不能发挥保护作用。而强化IPC使PGC-1α表达增加,恢复了对超氧化物歧化酶活性的调节能力,进而恢复了IPC对老年心肌的保护作用。
目的:本研究探索心肌缺血預適應(IPC)對老年大鼠心肌缺血再灌註(I/R)後的影響及機製。<br> 方法:取21~23月齡老年Wistar大鼠32隻,建立離體心髒Langendorff灌註模型,分為4組(每組8隻):對照組、I/R組、IPC組、彊化IPC組。對照組採用全心灌流180 min,不做任何處理。I/R組採用心髒平衡灌流30 min後,缺血30 min,再複灌120 min。IPC組採用心髒平衡灌流10 min,經兩次缺血5 min再灌註5 min後,缺血30 min,再複灌120 min。彊化IPC組採用心髒平衡灌流10 min,經四次缺血5 min再灌註5 min後,缺血30 min ,再複灌120 min。比較各組複灌30 min、60 min、90 min、120 min後心排血量的恢複率以及左心室髮展壓、左心室內壓最大上升和下降速率(±dp/dtmax)的恢複率;檢測缺血前及複灌120 min後冠狀動脈流齣液中肌痠激酶MB同工酶(CK-MB)和乳痠脫氫酶活性,心肌組織中丙二醛含量和超氧化物歧化酶的活性。各組取心尖肌做冰凍切片行過氧化物酶體增生激活受體γ協同刺激因子1α(PGC-1α)免疫組織化學染色,計算齣平均積分吸光度。<br> 結果:IPC組與I/R組丙二醛含量、CK-MB及超氧化物歧化酶活性,左心室髮展壓、±dp/dtmax恢複率比較差異無統計學意義(P>0.05),而彊化IPC組與I/R組比較,CK-MB和超氧化物歧化酶活性明顯減少(P<0.01),丙二醛含量明顯降低(P<0.05),超氧化物歧化酶活性明顯增加(P<0.01),心排血量、左心室髮展壓、±dp/dtmax恢複率明顯增加(P<0.01),差異有統計學意義。PGC-1α的錶達:IPC組與I/R組比較差異無統計學意義(P>0.05),而彊化IPC組錶達明顯增加,與I/R組比較差異有統計學意義(P<0.01)。<br> 結論:老年大鼠心肌IPC的保護作用減弱,可能機製是老年心肌PGC-1α蛋白錶達降低,使老年心肌調節超氧化物歧化酶活性的作用下降,進而影響老年心肌對應激反應的防護能力,使IPC對老年心肌不能髮揮保護作用。而彊化IPC使PGC-1α錶達增加,恢複瞭對超氧化物歧化酶活性的調節能力,進而恢複瞭IPC對老年心肌的保護作用。
목적:본연구탐색심기결혈예괄응(IPC)대노년대서심기결혈재관주(I/R)후적영향급궤제。<br> 방법:취21~23월령노년Wistar대서32지,건립리체심장Langendorff관주모형,분위4조(매조8지):대조조、I/R조、IPC조、강화IPC조。대조조채용전심관류180 min,불주임하처리。I/R조채용심장평형관류30 min후,결혈30 min,재복관120 min。IPC조채용심장평형관류10 min,경량차결혈5 min재관주5 min후,결혈30 min,재복관120 min。강화IPC조채용심장평형관류10 min,경사차결혈5 min재관주5 min후,결혈30 min ,재복관120 min。비교각조복관30 min、60 min、90 min、120 min후심배혈량적회복솔이급좌심실발전압、좌심실내압최대상승화하강속솔(±dp/dtmax)적회복솔;검측결혈전급복관120 min후관상동맥류출액중기산격매MB동공매(CK-MB)화유산탈경매활성,심기조직중병이철함량화초양화물기화매적활성。각조취심첨기주빙동절편행과양화물매체증생격활수체γ협동자격인자1α(PGC-1α)면역조직화학염색,계산출평균적분흡광도。<br> 결과:IPC조여I/R조병이철함량、CK-MB급초양화물기화매활성,좌심실발전압、±dp/dtmax회복솔비교차이무통계학의의(P>0.05),이강화IPC조여I/R조비교,CK-MB화초양화물기화매활성명현감소(P<0.01),병이철함량명현강저(P<0.05),초양화물기화매활성명현증가(P<0.01),심배혈량、좌심실발전압、±dp/dtmax회복솔명현증가(P<0.01),차이유통계학의의。PGC-1α적표체:IPC조여I/R조비교차이무통계학의의(P>0.05),이강화IPC조표체명현증가,여I/R조비교차이유통계학의의(P<0.01)。<br> 결론:노년대서심기IPC적보호작용감약,가능궤제시노년심기PGC-1α단백표체강저,사노년심기조절초양화물기화매활성적작용하강,진이영향노년심기대응격반응적방호능력,사IPC대노년심기불능발휘보호작용。이강화IPC사PGC-1α표체증가,회복료대초양화물기화매활성적조절능력,진이회복료IPC대노년심기적보호작용。
Objective: To explore the impact of Ischemic preconditioning (IPC) in aged experimental rats after myocardial ischemia-reperfusion (I/R) with its mechanism. <br> Methods: A total of 32 Wistar rats at the age of (21-23) months were divided into 4 groups, n=8 in each group.①Control group, the rats received cardiac perfusion for 180 min. ②I/R group, the rats received cardiac perfusion for 30 min, followed by ischemia for 30 min, then reperfusion for 120min.③IPC group, the rats received cardiac perfusion for 10 min, followed by ischemia and reperfusion 2 times (5 min in each time), then ischemia 30 min and reperfusion 120 min. ④ Enhanced IPC group, rats received cardiac perfusion for 10 min, followed by ischemia and reperfusion 4 times (5 min in each time), then ischemia 30 min and reperfusion 120 min. The recovery rate of cardiac output (CO), left ventricular developed pressure (LVDP) and the recovery rate of maximum rise and fall of left ventricular pressure (±dp/dtmax) at (30, 60, 90, 120) min after reperfusion were recorded respectively. The creatine kinase (CK-MB), superoxide dismutase (SOD) activity and malondialdehyde (MDA) content were examined before ischemia and 120 min after reperfusion. The apical peroxisome proliferator-activated receptorγco-stimulatory factor 1α(PGC-1α) was examined by immuno-histochemistry. <br> Results: The MDA content, CK-MB, SOD activities LVDP and (±dp/dtmax) recovery were similar between IPC group and I/R group, P>0.05. While compared with I/R group, the Enhanced IPC group showed decreased CK-MB activity and MDA content, increased SOD activity and CO, LVDP and (±dp/dtmax) recovery rate, all P<0.01. The PGC-1αexpression was similar between IPC group and I/R group, P>0.05. While compared with I/R group, the Enhanced IPC group had increased PGC-1αexpression, P<0.01. <br> Conclusion: The cardiac IPC was weakened in aged rats which might be because of decreased PGC-1αexpression, the enhanced IPC may up-regulate PGC-1αexpression and therefore, protect the cardiac tissue in aged experimental rats.