CAJ | 학술논문

目的通过建立心肌梗死(MI)后抑郁大鼠模型,检测心室颤动(室颤)阈值及心肌细胞N-甲基-D-门冬氨酸(N Methyl D Aspartate,NMDA)受体亚基(NMDAR1)、Kv4.2的表达情况,探讨NMDA受体在心肌梗死后抑郁大鼠心电生理异常中的作用.方法将50只SD大鼠随机均分为对照组、抑郁组(MDD组)、心肌梗死组(MI组)、MI后抑郁组(MI+MDD组)和氟西汀组(F组).通过结扎冠状动脉和慢性不可预见性温和应激,建立MI和抑郁大鼠模型,并运用心电图、Masson染色、糖水偏好实验和旷场实验对模型进行鉴定.采用S1S1程序电刺激左心室,测量各组大鼠室颤阈值.通过免疫组化法半定量各组大鼠心肌细胞NMDAR1、Kv4.2的表达.结果 ①心电图、Masson染色、糖水偏好实验和旷场实验结果显示模型制作成功；②与对照组[(8.3±0.7)V]相比,MI组、MDD组、MI+MDD组室颤阈值降低,F组室颤阈值升高[(5.2±0.9)V、(7.4±0.6)V、(4.0±0.5)V、(12.0±0.3)v],差异有统计学意义(P＜0.05),其中MI+MDD组最低；③免疫组化结果:MDD组和MI+MDD组大鼠心肌细胞内NMDAR1呈强阳性表达,显著高于其他3组,F组表达量最低；各组大鼠心肌细胞中均可见Kv4.2阳性表达,对照组的表达量最高,MI+MDD组的表达量最低,F组较MI+MDD组表达增加.结论心肌细胞NMDA受体过度表达和Kv4.2表达下降可能是MI后抑郁大鼠心电生理异常的分子机制之一.
목적 통과건립심기경사(MI)후억욱대서모형,검측심실전동(실전)역치급심기세포N-갑기-D-문동안산(N Methyl D Aspartate,NMDA)수체아기(NMDAR1)、Kv4.2적표체정황,탐토NMDA수체재심기경사후억욱대서심전생리이상중적작용.방법 장50지SD대서수궤균분위대조조、억욱조(MDD조)、심기경사조(MI조)、MI후억욱조(MI+MDD조)화불서정조(F조).통과결찰관상동맥화만성불가예견성온화응격,건립MI화억욱대서모형,병운용심전도、Masson염색、당수편호실험화광장실험대모형진행감정.채용S1S1정서전자격좌심실,측량각조대서실전역치.통과면역조화법반정량각조대서심기세포NMDAR1、Kv4.2적표체.결과 ①심전도、Masson염색、당수편호실험화광장실험결과현시모형제작성공；②여대조조[(8.3±0.7)V]상비,MI조、MDD조、MI+MDD조실전역치강저,F조실전역치승고[(5.2±0.9)V、(7.4±0.6)V、(4.0±0.5)V、(12.0±0.3)v],차이유통계학의의(P＜0.05),기중MI+MDD조최저；③면역조화결과:MDD조화MI+MDD조대서심기세포내NMDAR1정강양성표체,현저고우기타3조,F조표체량최저；각조대서심기세포중균가견Kv4.2양성표체,대조조적표체량최고,MI+MDD조적표체량최저,F조교MI+MDD조표체증가.결론 심기세포NMDA수체과도표체화Kv4.2표체하강가능시MI후억욱대서심전생리이상적분자궤제지일.
Objective To detect the ventricular fibrillation threshold and the expression of N Methyl D Aspartate receptor NMDAR1 and Kv4,.2 through establishing rat model of depression after myocardial infarction,to investigate the effects of NMDA receptor on cardiac electrophysiological abnormalities in rat with depression after myocardial infarction.Methods (①Fifty SD rats were randomly divided into N group (normal group),MDD group (depression group),MI group (myocardial infarction group),MI+MDD group (depression after myocardial infarction group) and F group(fluoxetine group),10 rats in each group.②By ligation of the left anteriordescending coronary artery to build model of myocardial infarction,and set in chronic unpredictable mild stress to build a model of depression,the ECG,Masson staining,sugar preference experiments and open field test were used to identify thesemodels.③The ventricular fibrillation threshold (VFF) was obtained thought the S1 S1 left ventricle electrical stimulation program.④Immunohistochemistry was used for quantifing the expression of NMDAR and Kv4.2.Results The results of ECG,HE staining,Masson staining,sugar preference experiments and the open field test show that the model was successful.(② the VFT in three groups(MI group,MDD group and MI+MDD group) was lower than N group,the VFT in F group was higher than that in N group(8.3±0.7) V、(5.2±0.9) V、(7.4±0.6) V、(4.0±0.5) V、(12.0±0.3) V,respectively (P＜0.05).③The immunohistochemical staining results:the myocardial cells expression of NMDAR1 was strongly positive in MDD group and MI+ MDD group,and was significantly higher than that in the other three groups.It was the lowest in F group.The expression of Kv4.2 was visible in each group,it was the highest in the normal group while it was the lowest in 9MI+MDD group.Conclusion The over expression of NMDAR1 and decreased expression of Kv4.2 may be one of the molecular mechanisms of cardiac electrophysiological abnormalities in rat with depression after myocardial infarction.