中华急诊医学杂志
中華急診醫學雜誌
중화급진의학잡지
CHINESE JOURNAL OF EMERGENCY MEDICINE
2009年
5期
483-487
,共5页
李健%安毅%毛晓波%曾秋棠%徐庆科%李丹
李健%安毅%毛曉波%曾鞦棠%徐慶科%李丹
리건%안의%모효파%증추당%서경과%리단
吡格列酮%心肌梗死面积%线粒体ATP敏感性钾通道%P38MAPK%JNK%NFκB P65
吡格列酮%心肌梗死麵積%線粒體ATP敏感性鉀通道%P38MAPK%JNK%NFκB P65
필격렬동%심기경사면적%선립체ATP민감성갑통도%P38MAPK%JNK%NFκB P65
Pioglitazone%infarct size%Mitochondrial ATP-sensitive potassium channel%P38MAPK%JNK%NFκB P65
目的 观察PPARγ激动剂吡格列酮对在体大鼠心肌缺血-再灌注心肌梗死面积、缺血面积及线粒体ATP敏感性钾通道(mitoKATP)影响,探讨其可能机制.方法 健康雄性SD大鼠54只,分为实验一和实验二完成.在实验一中24只大鼠随机分4组,每组6只:(1)假手术对照组(SO)行冠脉穿线但不结扎,4 h后取出心脏;(2)单纯I/R组于I/R前24 h由尾静脉注入0.9%生理盐水,开胸结扎冠脉前降支30 min,松解后再灌注4 h;(3)5-HD+吡格列酮组(5-HD+Pio)于I/R前24 h由尾静脉缓慢注入mitoKATP阻滞剂5羟基葵酸(10 ms/ks),30 min后再缓慢注入吡格列酮(3 mg/kg),持续5 min,24 h后处理同I/R组;(4)吡格列酮预处理组(Pio)于缺血-再灌注前24 h只注入吡格列酮(3 mg/kg),持续5min,余处理同(3).后三组结扎前降支30 min、再灌注4 h后取出心脏.Western blot法测P38MAPK、JNK和NFκB P65蛋白水平的表达.在实验二中SD大鼠30只,分为SO组、I/R组、Pio组、5-HD+Pio组及单纯5-HD组(于I/R前24 h由尾静脉缓慢注入5羟基葵酸10 mg/kg余同I/R组),再灌注4 h后,测心肌缺血及梗死范围.多组间比较采用单因素方差分析(SNK-q检验),采用SPSS 11.0软件系统分析,P<0.05为差异具有统计学意义.结果 (1)与I/R组(34.93±5.55)%相比,Pio组梗死面积(20.24±3.93%)明显减少(P<0.05),5-HD+Pio组和5-HD与I/R组相比差异无统计学意义(P>0.05);除SO组外,其他各绀间心肌缺血面积差异无统计学意义(P>0.05).与SO组相比,I/R组P38MAPKmRNA、JNK mRNA及P38MAPK、JNKI、JNK2和NFκB P65蛋白表达水平明显增加(P<0.05);与I/R组相比Pio绀能抑制以上水平的过度表达(P<0.05).结论 吡格列酮预处理可通过减少心肌梗死范围起到抗缺血-再灌注损伤作用,该保护作用可能与开放线粒体ATP敏感性钾通道及下调P38MAPK、JNK及NF-κB P65蛋白表达活性有关.
目的 觀察PPARγ激動劑吡格列酮對在體大鼠心肌缺血-再灌註心肌梗死麵積、缺血麵積及線粒體ATP敏感性鉀通道(mitoKATP)影響,探討其可能機製.方法 健康雄性SD大鼠54隻,分為實驗一和實驗二完成.在實驗一中24隻大鼠隨機分4組,每組6隻:(1)假手術對照組(SO)行冠脈穿線但不結扎,4 h後取齣心髒;(2)單純I/R組于I/R前24 h由尾靜脈註入0.9%生理鹽水,開胸結扎冠脈前降支30 min,鬆解後再灌註4 h;(3)5-HD+吡格列酮組(5-HD+Pio)于I/R前24 h由尾靜脈緩慢註入mitoKATP阻滯劑5羥基葵痠(10 ms/ks),30 min後再緩慢註入吡格列酮(3 mg/kg),持續5 min,24 h後處理同I/R組;(4)吡格列酮預處理組(Pio)于缺血-再灌註前24 h隻註入吡格列酮(3 mg/kg),持續5min,餘處理同(3).後三組結扎前降支30 min、再灌註4 h後取齣心髒.Western blot法測P38MAPK、JNK和NFκB P65蛋白水平的錶達.在實驗二中SD大鼠30隻,分為SO組、I/R組、Pio組、5-HD+Pio組及單純5-HD組(于I/R前24 h由尾靜脈緩慢註入5羥基葵痠10 mg/kg餘同I/R組),再灌註4 h後,測心肌缺血及梗死範圍.多組間比較採用單因素方差分析(SNK-q檢驗),採用SPSS 11.0軟件繫統分析,P<0.05為差異具有統計學意義.結果 (1)與I/R組(34.93±5.55)%相比,Pio組梗死麵積(20.24±3.93%)明顯減少(P<0.05),5-HD+Pio組和5-HD與I/R組相比差異無統計學意義(P>0.05);除SO組外,其他各紺間心肌缺血麵積差異無統計學意義(P>0.05).與SO組相比,I/R組P38MAPKmRNA、JNK mRNA及P38MAPK、JNKI、JNK2和NFκB P65蛋白錶達水平明顯增加(P<0.05);與I/R組相比Pio紺能抑製以上水平的過度錶達(P<0.05).結論 吡格列酮預處理可通過減少心肌梗死範圍起到抗缺血-再灌註損傷作用,該保護作用可能與開放線粒體ATP敏感性鉀通道及下調P38MAPK、JNK及NF-κB P65蛋白錶達活性有關.
목적 관찰PPARγ격동제필격렬동대재체대서심기결혈-재관주심기경사면적、결혈면적급선립체ATP민감성갑통도(mitoKATP)영향,탐토기가능궤제.방법 건강웅성SD대서54지,분위실험일화실험이완성.재실험일중24지대서수궤분4조,매조6지:(1)가수술대조조(SO)행관맥천선단불결찰,4 h후취출심장;(2)단순I/R조우I/R전24 h유미정맥주입0.9%생리염수,개흉결찰관맥전강지30 min,송해후재관주4 h;(3)5-HD+필격렬동조(5-HD+Pio)우I/R전24 h유미정맥완만주입mitoKATP조체제5간기규산(10 ms/ks),30 min후재완만주입필격렬동(3 mg/kg),지속5 min,24 h후처리동I/R조;(4)필격렬동예처리조(Pio)우결혈-재관주전24 h지주입필격렬동(3 mg/kg),지속5min,여처리동(3).후삼조결찰전강지30 min、재관주4 h후취출심장.Western blot법측P38MAPK、JNK화NFκB P65단백수평적표체.재실험이중SD대서30지,분위SO조、I/R조、Pio조、5-HD+Pio조급단순5-HD조(우I/R전24 h유미정맥완만주입5간기규산10 mg/kg여동I/R조),재관주4 h후,측심기결혈급경사범위.다조간비교채용단인소방차분석(SNK-q검험),채용SPSS 11.0연건계통분석,P<0.05위차이구유통계학의의.결과 (1)여I/R조(34.93±5.55)%상비,Pio조경사면적(20.24±3.93%)명현감소(P<0.05),5-HD+Pio조화5-HD여I/R조상비차이무통계학의의(P>0.05);제SO조외,기타각감간심기결혈면적차이무통계학의의(P>0.05).여SO조상비,I/R조P38MAPKmRNA、JNK mRNA급P38MAPK、JNKI、JNK2화NFκB P65단백표체수평명현증가(P<0.05);여I/R조상비Pio감능억제이상수평적과도표체(P<0.05).결론 필격렬동예처리가통과감소심기경사범위기도항결혈-재관주손상작용,해보호작용가능여개방선립체ATP민감성갑통도급하조P38MAPK、JNK급NF-κB P65단백표체활성유관.
Objective To observe the effects of preconditioning with pioglitazone on infarct size and mito-chondrial ATP-sensitive potassium channel in rats with ischemia-repedusion, and to explore its possible mecha-nism. Method The whole experiment was divided into experiment Ⅰ and Ⅱ. In experiment Ⅰ, 24 rats were ran-domly divided into four groups (6 rats in each group): (1)Sham-operated (SO) group: the coronary artery of rat was threading without hgation, and the heart was removed by cutting immediately 4 hours later; (2) Isehemia-reperfusion (I/R) group: the rats were administered with 0.9% saline intravenously via caudal vein at 24 hours before iigating the left anterior descending branch of coronary artery for 30 minutes, and followed by reperfusion for 4 hours; (3)5-hydroxydecanoate plus pioglitazone(5HD+Pio) group: the rats were injected with 10 mg/kg 5-hy-droxydecanoate (the blocker of mitochondrial ATP-sensitive potassium channels,) at 24 hours before ligation, and 30 minutes later, 3 mg/kg pioglitazone was given in 5 minutes, and then the rats were subjected to ischemia for 30 minutes, followed by reperfusion for4 hours; (4)pioglitazone treatment group (Pio): the mrs were given 3 mg/kg pioglitazone at 24 hours before occlusion, and then they were treated as done in the 5HD+Pio group. In I/R, 5HD+Pio and Pio group, the hearts were removed by cutting after reperfusion. Western blotting was used to detect the protein expression of P38MAPK, .INK and NFκB P65. In experiment Ⅱ, 30 rats were randomly divided into five groups: SO, I/R, Pio, 5HD+Pio and 5-HD group (rats were treated as done in the rats of I/R group and were injected with 10 mg/kg 5-bydroxydecanoate 24 h before ischemia/reperfusion),and the size of myocardial in-farction and isehemia were measured after reperfusion. Statistical analyses were performed using SPSS10.0 soft-ware. Multiple comparisons were analyzed by one-way analysis of variance (SNK-q test). P<0.05 was consid-ered statistically significant. Results (1) The infarct size in i/R group was(34.93±5.55)%, while pioglita-zone reduced the infarct size to(20.24±3.93)% (P<0.05). There was no significant difference between I/R and 5-HD±Pio or 5-HD groups (P>0.05). Compared with the sham-operated group, the expression of P38MAPKmRNA, JNKmRNA and protein of P38MAPK, JNK and NFκB P65 in I/R increased (P<0.05). Com-pared with the I/R group, pioglitazone inhibited these undue expressions (P<0.05). Conclusions Pioglitazone could protect the heart from ischemia-reperfusion injury evidenced by reducing infarct size. These protective effects of pioglitazone may be related to opening mitochondrial ATP-seusitive potassium channels or downregulation of JNK and p38 MAPK signaling, leading to the overexpression of NFκB p65 activation.
