中华心血管病杂志
中華心血管病雜誌
중화심혈관병잡지
Chinese Journal of Cardiology
2014年
10期
866-872
,共7页
蔡文科%张燕%李吉国%王健
蔡文科%張燕%李吉國%王健
채문과%장연%리길국%왕건
心肌再灌注损伤%受体,阿片样,κ%Toll样受体4%NF-κB
心肌再灌註損傷%受體,阿片樣,κ%Toll樣受體4%NF-κB
심기재관주손상%수체,아편양,κ%Toll양수체4%NF-κB
Myocardial reperfusion injury%Receptors,opioid,kappa%Toll-like receptor 4%NF-kappa B
目的 研究选择性κ阿片受体(κ-opioid receptor,κ-OR)激动剂U50,488H对大鼠缺血再灌注心肌的保护作用,及其与Toll样受体4(TLR4)/核因子-κB(NF-κB)信号通路的关系.方法 成年健康雄性SD大鼠,体质量250 ～ 300 g,由第四军医大学动物实验中心提供.采用随机区组法将大鼠分为未阻断左前降支血流的对照组,心肌缺血再灌注组(I/R组),使用U50,488H的心肌缺血再灌注组(I/R+ U50组)以及加用κ-OR特异性阻断剂Nor-BNI和U50,488H的心肌缺血再灌注组(I/R+ U50+N组).使用丝线短暂阻断大鼠冠状动脉左前降支血流30 min,再灌注120 min,建立大鼠心肌缺血再灌注模型.在缺血前由静脉选择注射U50,488H和(或)κ-OR激动剂的阻断剂(Nor-BNI).对照组接受相同的手术过程,但未阻断左前降支血流.采用伊文思蓝和TTC染色检测大鼠心肌梗死面积.观察心律失常发生情况并计算心律失常评分.灌注结束后分别选取心肌梗死后的梗死区域、缺血区域、临近缺血区域的正常心肌区域(危险区域)检测TLR4、NF-κB、肿瘤坏死因-α(TNF-α)和髓过氧化物酶(MPO)的表达水平.结果 I/R+ U50组大鼠心肌梗死面积小于I/R组(P＜0.01),而I/R+U50+N组则大于I/R+ U50组(P＜0.01).I/R+ U50组大鼠室性心动过速和心室颤动的发生率均低于I/R组(P均＜0.01),心律失常评分亦低于I/R组(2.9±0.7比4.4±0.9,P＜0.05).而I/R+ U50+N组室性心动过速和心室颤动的发生率均高于I/R+U50组(P均＜0.01),心律失常评分亦高于I/R+ U50组(4.5±0.8比2.9±0.7,P＜0.01).I/R+ U50组大鼠心肌缺血区域和危险区域中的TLR4、NF-κB、TNF-α和MPO的表达水平均低于I/R组(P均＜0.01),而I/R+ U50+N组则均高于I/R+ U50组(P均＜0.01).结论 κ-OR激动剂U50,488H对大鼠缺血再灌注心肌具有保护作用,且该作用可能是通过TLR4/NF-κB信号通路实现的.
目的 研究選擇性κ阿片受體(κ-opioid receptor,κ-OR)激動劑U50,488H對大鼠缺血再灌註心肌的保護作用,及其與Toll樣受體4(TLR4)/覈因子-κB(NF-κB)信號通路的關繫.方法 成年健康雄性SD大鼠,體質量250 ～ 300 g,由第四軍醫大學動物實驗中心提供.採用隨機區組法將大鼠分為未阻斷左前降支血流的對照組,心肌缺血再灌註組(I/R組),使用U50,488H的心肌缺血再灌註組(I/R+ U50組)以及加用κ-OR特異性阻斷劑Nor-BNI和U50,488H的心肌缺血再灌註組(I/R+ U50+N組).使用絲線短暫阻斷大鼠冠狀動脈左前降支血流30 min,再灌註120 min,建立大鼠心肌缺血再灌註模型.在缺血前由靜脈選擇註射U50,488H和(或)κ-OR激動劑的阻斷劑(Nor-BNI).對照組接受相同的手術過程,但未阻斷左前降支血流.採用伊文思藍和TTC染色檢測大鼠心肌梗死麵積.觀察心律失常髮生情況併計算心律失常評分.灌註結束後分彆選取心肌梗死後的梗死區域、缺血區域、臨近缺血區域的正常心肌區域(危險區域)檢測TLR4、NF-κB、腫瘤壞死因-α(TNF-α)和髓過氧化物酶(MPO)的錶達水平.結果 I/R+ U50組大鼠心肌梗死麵積小于I/R組(P＜0.01),而I/R+U50+N組則大于I/R+ U50組(P＜0.01).I/R+ U50組大鼠室性心動過速和心室顫動的髮生率均低于I/R組(P均＜0.01),心律失常評分亦低于I/R組(2.9±0.7比4.4±0.9,P＜0.05).而I/R+ U50+N組室性心動過速和心室顫動的髮生率均高于I/R+U50組(P均＜0.01),心律失常評分亦高于I/R+ U50組(4.5±0.8比2.9±0.7,P＜0.01).I/R+ U50組大鼠心肌缺血區域和危險區域中的TLR4、NF-κB、TNF-α和MPO的錶達水平均低于I/R組(P均＜0.01),而I/R+ U50+N組則均高于I/R+ U50組(P均＜0.01).結論 κ-OR激動劑U50,488H對大鼠缺血再灌註心肌具有保護作用,且該作用可能是通過TLR4/NF-κB信號通路實現的.
목적 연구선택성κ아편수체(κ-opioid receptor,κ-OR)격동제U50,488H대대서결혈재관주심기적보호작용,급기여Toll양수체4(TLR4)/핵인자-κB(NF-κB)신호통로적관계.방법 성년건강웅성SD대서,체질량250 ～ 300 g,유제사군의대학동물실험중심제공.채용수궤구조법장대서분위미조단좌전강지혈류적대조조,심기결혈재관주조(I/R조),사용U50,488H적심기결혈재관주조(I/R+ U50조)이급가용κ-OR특이성조단제Nor-BNI화U50,488H적심기결혈재관주조(I/R+ U50+N조).사용사선단잠조단대서관상동맥좌전강지혈류30 min,재관주120 min,건립대서심기결혈재관주모형.재결혈전유정맥선택주사U50,488H화(혹)κ-OR격동제적조단제(Nor-BNI).대조조접수상동적수술과정,단미조단좌전강지혈류.채용이문사람화TTC염색검측대서심기경사면적.관찰심률실상발생정황병계산심률실상평분.관주결속후분별선취심기경사후적경사구역、결혈구역、림근결혈구역적정상심기구역(위험구역)검측TLR4、NF-κB、종류배사인-α(TNF-α)화수과양화물매(MPO)적표체수평.결과 I/R+ U50조대서심기경사면적소우I/R조(P＜0.01),이I/R+U50+N조칙대우I/R+ U50조(P＜0.01).I/R+ U50조대서실성심동과속화심실전동적발생솔균저우I/R조(P균＜0.01),심률실상평분역저우I/R조(2.9±0.7비4.4±0.9,P＜0.05).이I/R+ U50+N조실성심동과속화심실전동적발생솔균고우I/R+U50조(P균＜0.01),심률실상평분역고우I/R+ U50조(4.5±0.8비2.9±0.7,P＜0.01).I/R+ U50조대서심기결혈구역화위험구역중적TLR4、NF-κB、TNF-α화MPO적표체수평균저우I/R조(P균＜0.01),이I/R+ U50+N조칙균고우I/R+ U50조(P균＜0.01).결론 κ-OR격동제U50,488H대대서결혈재관주심기구유보호작용,차해작용가능시통과TLR4/NF-κB신호통로실현적.
Objective To observe the effects of κ-opioid receptor agonist U50,488H on myocardial ischemia and reperfusion injury and related mechanism.Methods Rats were randomly divided into sham operation,myocardial ischemia and reperfusion(I/R,30 min ischemia followed by 120 min reperfusion),and MI/R + U50,488H (1.5 mg/kg) and I/R + U50,488H + selective κ-opioid receptor antagonist Nor-BNI (2 mg/kg,n =8 each).The infarction size and the incidence of ventricular arrhythmias were observed.Real-time PCR and DAB staining were used to define the myocardium Toll-like receptor 4 (TLR4)expression.Myeloperoxidase level,TNF-α induction and the expression of NF-κB were also examined in rats.Results After I/R,the expressions of myocardial TLR4 and NF-κB increased significantly both in ischemia area and area at risk.Compared with I/R,κ-opioid receptor stimulation with U50,488H significantly attenuated the expressions of TLR4 and NF-κB and reduced myeloperoxidase (MPO) levels,myocardial TNF-α production,myocardial infarct sizes and the incidence of ventricular arrhythmias and arrhythmia score (2.9 ± 0.7 vs.4.4 ± 0.9,P ＜ 0.05),above effects of U50,488H were partly abolished by co-treatment with Nor-BNI.Conclusion These data provide evidence for the first time that κ-opioid receptor stimulation could attenuate myocardial L/R injury via downregulating TLR4/NF-κB signaling in rats.
