CAJ | 학술논문

目的探讨螺内酯对心力衰竭犬心房颤动(房颤)的影响及其作用机制.方法 21只犬随机分为3组:假手术组(n=7)、起搏组(n=7)和螺内酯组(n=7).采用心室快速起搏建立心力衰竭犬模型.假手术组植入起搏器后不起搏;起搏组和螺内酯组以220次/min快速起搏心室6周;螺内酯组起搏前1周给予螺内酯至起搏后6周.通过缝置于左、右心房的4对电极测定房颤诱发次数及持续时间,超声心动图测定心房、心室结构和功能变化,Masson染色测定心房胶原容积分数,Western blot半定量分析心房肌基质金属蛋白酶-9(MMP-9)、转化生长因子-β1(TGF-β1)及血小板衍生生长因子(PDGF)蛋白含量.结果 (1)心室快速起搏6周后,起搏组犬房颤诱发率和持续时间显著增加(P<0.01),螺内酯组房颤诱发率显著降低、持续时间显著缩短(P<0.05).(2)与假手术组相比,起搏组犬左心室最大容积(LVVmax)及左心房最大容积(LAVmax)显著增加(P<0.01),左心房射血分数(LAEF)及左心室射血分数(LVEF)显著降低(P<0.01),螺内酯组犬LVVmax、LAVmax显著缩小(P<0.01),LAEF及LVEF显著升高(P<0.01).(3)与假手术组相比,起搏组犬心房胶原容积分数显著升高(P<0.01),TGF-β1、PDGF、MMP-9蛋白质表达量显著增加(P<0.05);与起搏组相比,螺内酯组胶原容积分数显著降低(P<0.01),TGF-β1、PDGF、MMP-9蛋白表达量显著减少(P<0.01).结论螺内酯可以减少心力衰竭后房颤的发生,其机制可能与抑制心房肌PDGF、TGF-β表达有关.
목적 탐토라내지대심력쇠갈견심방전동(방전)적영향급기작용궤제.방법 21지견수궤분위3조:가수술조(n=7)、기박조(n=7)화라내지조(n=7).채용심실쾌속기박건립심력쇠갈견모형.가수술조식입기박기후불기박;기박조화라내지조이220차/min쾌속기박심실6주;라내지조기박전1주급여라내지지기박후6주.통과봉치우좌、우심방적4대전겁측정방전유발차수급지속시간,초성심동도측정심방、심실결구화공능변화,Masson염색측정심방효원용적분수,Western blot반정량분석심방기기질금속단백매-9(MMP-9)、전화생장인자-β1(TGF-β1)급혈소판연생생장인자(PDGF)단백함량.결과 (1)심실쾌속기박6주후,기박조견방전유발솔화지속시간현저증가(P<0.01),라내지조방전유발솔현저강저、지속시간현저축단(P<0.05).(2)여가수술조상비,기박조견좌심실최대용적(LVVmax)급좌심방최대용적(LAVmax)현저증가(P<0.01),좌심방사혈분수(LAEF)급좌심실사혈분수(LVEF)현저강저(P<0.01),라내지조견LVVmax、LAVmax현저축소(P<0.01),LAEF급LVEF현저승고(P<0.01).(3)여가수술조상비,기박조견심방효원용적분수현저승고(P<0.01),TGF-β1、PDGF、MMP-9단백질표체량현저증가(P<0.05);여기박조상비,라내지조효원용적분수현저강저(P<0.01),TGF-β1、PDGF、MMP-9단백표체량현저감소(P<0.01).결론 라내지가이감소심력쇠갈후방전적발생,기궤제가능여억제심방기PDGF、TGF-β표체유관.
Objective To investigate the effect and mechanism of spironolaetone,an aldosterone antagonist,in preventing atrial fibrillation (AF) in congestive heart failure (CHF) dogs induced by chronic rapid ventricular pacing.Methods Twenty-one dogs were randomly divided into sham-operated group(n=7),pacing group(n=7),and spironolactone group (n=7).A pacemaker (VOO) was implanted in a subcutaneous pocket and attached to a screw-in epicardial lead in the apex of right ventricular.The dogs in pacing group and spironolactone group were paced at 220 beats per minutes for 6 weeks.the dogs in spimnolactone group received spironolactone from 1 week before rapid ventricular pacing to pacing stop.One thin silicon plaque containing 4 pairs of electrodes was sutured to each atrium.The inducibility and duration of AF were meagured in all groups.Transthoracic echocardiographic examinations were performed to detect structural and functional changes of atrium and ventficulat.Atrial fibrosis was quantified with Magson staining.The protein levels of MMP-9,TGF-β1 and PDGF in atrium were assessed by western blot Results (1) After rapid ventricular pacing for 6 weeks,the inducibility and duration of AF increased significantly (P<0.01),while they decreased effectively after spironolactone treatment.(2)In pacing group,LVVmax and LAVmax increased significantly (P<0.01),LAEF and LVEF decreased significantly compared to sham-operated group (P<0.01).In spimnolactone group,LVVmax and LAVmax decreased significantly (P<0.01),while LAEF and LVEF increased significantly (P<0.01).(3)In pacing group,volume fraction of collagen increased significantly (P<0.01),as well as the proteinlevels of MMP-9, TGF-β1 and PDGF(P <0. 01 ). In spironolactone group, volume fraction of collagen decreased significantly(P <0. 01 ) ,together with the protein levels of MMP-9 ,TGF-β1 and PDGF( P <0.01 ). Conclusion Spironolactone could reduce the incidence of atrial fibrillation in congestive heart failure,the mechanism may be related to the suppression of PDGF and TGF-β1 in atria.