CAJ | 학술논문

目的应用大鼠在体心肌梗死后心室重构模型，探讨不同时间段重组人促红细胞生成素（recombinant human erythropoietin, rHu-EPO）对心肌梗死大鼠血流动力学、心功能及左室梗死面积的影响．探讨EPO抑制心肌梗死后心脏重构的给药时机和方案，为临床应用提供实验依据．方法选取健康SD大鼠60只，随机分为假手术组、单纯心肌梗死后心脏重构组、不同药物干预组（rHu-EPO干预组、SB203580组、rHu-EPO+SB203580组）各5只．在冠状动脉前降支的上1/3点以上处穿线结扎，制作心肌梗死模型，喂养4周．不同药物干预组在缺血开始前皮下注射药物，以后每周2次．分别于术后24 h、2周、4周测定血流动力学参数，记录左室收缩压（LVSP）、左室舒张末压（LVEDP）、左室内压最大上升速率（+dp/dt）和左室内压最大下降速率（-dp/dt），并记录同步心率（HR）．4周后处死动物收集心脏标本，根据左右心室实际重量（LVW、RVW），计算左右心室相对重量（LV/BW、RV/BW）．TTC及伊文式蓝染色检测左室梗死面积、病理检测大体和镜下形态学改变．结果术后24 h：与假手术组相比，单纯心肌梗死后心脏重构组左室收缩压（LVSP）、左室舒张末期压（LVEDP）和左室内压最大上升和下降速率（±dp/dt）明显异常，LVSP、±dp/dt均显著降低，LVEDP显著升高（P＜0.05）；与单纯心肌梗死后心脏重构组相比，不同药物干预组（rHu-EPO干预组、SB203580组、rHu-EPO+SB203580组）±dp/dt有明显改善（P＜0.05）．术后2周：与假手术组相比，单纯心肌梗死后心脏重构组LVSP、LVEDP和±dp/dt显著恶化（P＜0.05）；与单纯心肌梗死后心脏重构组相比，不同药物干预组（rHu-EPO干预组、SB203580组、rHu-EPO+SB203580组）±dp/dt有显著改善（P＜0.05）．术后4周：与假手术组相比，单纯心肌梗死后心脏重构组LVSP、LVEDP和±dp/dt显著恶化（P＜0.05）；与单纯心肌梗死后心脏重构组相比，不同药物干预组（rHu-EPO干预组、SB203580组、rHu-EPO+SB203580组）±dp/dt有显著改善（P＜0.05）．与假手术组比较，单纯心肌梗死后心脏重构组LV/BW均上升，差异有统计学意义（P＜0.05）．与单纯心肌梗死后心脏重构组相比，不同药物干预组（rHu-EPO干预组、SB203580组、rHu-EPO+SB203580组） LV/BW均有所下降，差异有统计学意义（P＜0.05）．与单纯心肌梗死后心脏重构组相比，不同药物干预组（rHu-EPO干预组、SB203580组、rHu-EPO+SB203580组）心脏梗死面积显著缩小（P＜0.05）．结论 rH-EPO可通过改善AMI后大鼠的左室收缩及舒张功能，保护心功能．rH-EPO可通过降低AMI后大鼠心室相对重量、缩小梗死面积、促进梗死交界区毛细血管新生，达到抑制心室重构. 目的應用大鼠在體心肌梗死後心室重構模型，探討不同時間段重組人促紅細胞生成素（recombinant human erythropoietin, rHu-EPO）對心肌梗死大鼠血流動力學、心功能及左室梗死麵積的影響．探討EPO抑製心肌梗死後心髒重構的給藥時機和方案，為臨床應用提供實驗依據．方法選取健康SD大鼠60隻，隨機分為假手術組、單純心肌梗死後心髒重構組、不同藥物榦預組（rHu-EPO榦預組、SB203580組、rHu-EPO+SB203580組）各5隻．在冠狀動脈前降支的上1/3點以上處穿線結扎，製作心肌梗死模型，餵養4週．不同藥物榦預組在缺血開始前皮下註射藥物，以後每週2次．分彆于術後24 h、2週、4週測定血流動力學參數，記錄左室收縮壓（LVSP）、左室舒張末壓（LVEDP）、左室內壓最大上升速率（+dp/dt）和左室內壓最大下降速率（-dp/dt），併記錄同步心率（HR）．4週後處死動物收集心髒標本，根據左右心室實際重量（LVW、RVW），計算左右心室相對重量（LV/BW、RV/BW）．TTC及伊文式藍染色檢測左室梗死麵積、病理檢測大體和鏡下形態學改變．結果術後24 h：與假手術組相比，單純心肌梗死後心髒重構組左室收縮壓（LVSP）、左室舒張末期壓（LVEDP）和左室內壓最大上升和下降速率（±dp/dt）明顯異常，LVSP、±dp/dt均顯著降低，LVEDP顯著升高（P＜0.05）；與單純心肌梗死後心髒重構組相比，不同藥物榦預組（rHu-EPO榦預組、SB203580組、rHu-EPO+SB203580組）±dp/dt有明顯改善（P＜0.05）．術後2週：與假手術組相比，單純心肌梗死後心髒重構組LVSP、LVEDP和±dp/dt顯著噁化（P＜0.05）；與單純心肌梗死後心髒重構組相比，不同藥物榦預組（rHu-EPO榦預組、SB203580組、rHu-EPO+SB203580組）±dp/dt有顯著改善（P＜0.05）．術後4週：與假手術組相比，單純心肌梗死後心髒重構組LVSP、LVEDP和±dp/dt顯著噁化（P＜0.05）；與單純心肌梗死後心髒重構組相比，不同藥物榦預組（rHu-EPO榦預組、SB203580組、rHu-EPO+SB203580組）±dp/dt有顯著改善（P＜0.05）．與假手術組比較，單純心肌梗死後心髒重構組LV/BW均上升，差異有統計學意義（P＜0.05）．與單純心肌梗死後心髒重構組相比，不同藥物榦預組（rHu-EPO榦預組、SB203580組、rHu-EPO+SB203580組） LV/BW均有所下降，差異有統計學意義（P＜0.05）．與單純心肌梗死後心髒重構組相比，不同藥物榦預組（rHu-EPO榦預組、SB203580組、rHu-EPO+SB203580組）心髒梗死麵積顯著縮小（P＜0.05）．結論 rH-EPO可通過改善AMI後大鼠的左室收縮及舒張功能，保護心功能．rH-EPO可通過降低AMI後大鼠心室相對重量、縮小梗死麵積、促進梗死交界區毛細血管新生，達到抑製心室重構.
목적응용대서재체심기경사후심실중구모형，탐토불동시간단중조인촉홍세포생성소（recombinant human erythropoietin, rHu-EPO）대심기경사대서혈류동역학、심공능급좌실경사면적적영향．탐토EPO억제심기경사후심장중구적급약시궤화방안，위림상응용제공실험의거．방법선취건강SD대서60지，수궤분위가수술조、단순심기경사후심장중구조、불동약물간예조（rHu-EPO간예조、SB203580조、rHu-EPO+SB203580조）각5지．재관상동맥전강지적상1/3점이상처천선결찰，제작심기경사모형，위양4주．불동약물간예조재결혈개시전피하주사약물，이후매주2차．분별우술후24 h、2주、4주측정혈류동역학삼수，기록좌실수축압（LVSP）、좌실서장말압（LVEDP）、좌실내압최대상승속솔（+dp/dt）화좌실내압최대하강속솔（-dp/dt），병기록동보심솔（HR）．4주후처사동물수집심장표본，근거좌우심실실제중량（LVW、RVW），계산좌우심실상대중량（LV/BW、RV/BW）．TTC급이문식람염색검측좌실경사면적、병리검측대체화경하형태학개변．결과술후24 h：여가수술조상비，단순심기경사후심장중구조좌실수축압（LVSP）、좌실서장말기압（LVEDP）화좌실내압최대상승화하강속솔（±dp/dt）명현이상，LVSP、±dp/dt균현저강저，LVEDP현저승고（P＜0.05）；여단순심기경사후심장중구조상비，불동약물간예조（rHu-EPO간예조、SB203580조、rHu-EPO+SB203580조）±dp/dt유명현개선（P＜0.05）．술후2주：여가수술조상비，단순심기경사후심장중구조LVSP、LVEDP화±dp/dt현저악화（P＜0.05）；여단순심기경사후심장중구조상비，불동약물간예조（rHu-EPO간예조、SB203580조、rHu-EPO+SB203580조）±dp/dt유현저개선（P＜0.05）．술후4주：여가수술조상비，단순심기경사후심장중구조LVSP、LVEDP화±dp/dt현저악화（P＜0.05）；여단순심기경사후심장중구조상비，불동약물간예조（rHu-EPO간예조、SB203580조、rHu-EPO+SB203580조）±dp/dt유현저개선（P＜0.05）．여가수술조비교，단순심기경사후심장중구조LV/BW균상승，차이유통계학의의（P＜0.05）．여단순심기경사후심장중구조상비，불동약물간예조（rHu-EPO간예조、SB203580조、rHu-EPO+SB203580조） LV/BW균유소하강，차이유통계학의의（P＜0.05）．여단순심기경사후심장중구조상비，불동약물간예조（rHu-EPO간예조、SB203580조、rHu-EPO+SB203580조）심장경사면적현저축소（P＜0.05）．결론 rH-EPO가통과개선AMI후대서적좌실수축급서장공능，보호심공능．rH-EPO가통과강저AMI후대서심실상대중량、축소경사면적、촉진경사교계구모세혈관신생，체도억제심실중구.
Objective Ventricular remodeling mode after myocardial infarction in rats was used to investigate the effects of recombinant human erythropoietin (rHu-EPO) on hemodynamic,ventricular function and infarct size of left ventricle in rats with myocardial infarction, so as to find out the optimum time and protocol of EPO treatment for ventricular remodeling after myocardial infarction and provide evidence for clinical application of EPO. Methods Sixty healthy male Sprague Dawley rats were divided randomly and equally into 5 groups:sham group,simple cardiac remodeling after myocardial infarction group, the intervention groups of different drugs ( rHu-EPO in the intervention group and SB203580 group,rHu-EPO+SB203580,group) . Ligation was set at more than 1/3 points on the anterior descending coronary artery to make model of myocardial infarction in rats, and the rats were feeded for four weeks. Different drugs in the intervention groups were subcutaneously injected once before ischemia and twice a week after ischemia. Respectively, 24 hours, 2 weeks, and 4 weeks after ischemia, we detected the hemodynamic parameters, recorded the left ventricular systolic pressure (LVSP), left ventricular end diastolic pressure (LVEDP), maximal rate of left ventricular pressure (+dp/dt) and left ventricular pressure decline rate (-dp/dt), and recorded the synchronization of heart rate (HR) . The animals were sacrificed 4 weeks after ischemia, and the heart specimens were collected. The relative weight of left and right ventricle (LV/BW in the RV/BW) was calculated according to the left and right ventricular weight (LVW, RVW) . TTC and Evans blue staining was used to detect left ventricular infarct size, and pathological examination was used to observe the gross and microscopic morphological change. Results 24 hours after operation: Compared with the sham group, in simply cardiac remodeling after myocardial infarction group, rats' left ventricular systolic pressure (LVSP), left ventricular end diastolic pressure (LVEDP) and left ventricular pressure maximum rise and fall rate (±dp/dt) was significantly abnormal,LVSP and ± dp/dt were significantly reduced, the LVEDP was significantly increased (P<0.05);compared with simply cardiac remodeling after myocardial infarction group, in the intervention groups (rHu-EPO in the intervention group, SB203580 group, rHu-the EPO + SB203580 group) rats' ± the dp /dt improved significantly (P<0.05) . After 2 weeks:compared with the sham group, in simple cardiac remodeling after myocardial infarction group rats’LVSP and LVEDP and ± dp/dt significant deterioration (P<0.05) ;compared with simply cardiac remodeling after myocardial infarction group, in the intervention group (rHu-EPO in the intervention group, SB203580 group, rHu-the EPO+SB203580 group) rats’± the dp/dt was significantly improved (P<0.05) . After 4 weeks:compared with the sham group, in simple cardiac remodeling after myocardial infarction group rats’LVSP and LVEDP and ± dp/dt significant deterioration (P<0.05) ; compared with simply cardiac remodeling after myocardial infarction group, in the intervention groups (rHu-EPO in the intervention group, SB203580 group, rHu-the EPO + SB203580 group) rats' ± the dp/dt was significantly improved (P<0.05) . Compared with the sham group, in simply cardiac remodeling after myocardial infarction group rats' LV/BW increased, the difference was statistically significant (P<0.05) . Compared with simply cardiac remodeling after myocardial infarction group,in the intervention group (rHu-EPO in the intervention group and SB203580 group, rHu-the EPO+SB203580 group) rats’LV/BW decreased, the difference was statistically significant (P<0.05 ) . Compared with simply after myocardial infarction cardiac remodeling group, in the intervention groups (rHu-EPO in the intervention group and SB203580 group,rHu-EPO+SB203580 group) rats’cardiac infarct size was significantly reduced (P<0.05). Conclusions rH-EPO can protect the heart function through improving the left ventricular systolic and diastolic function after AMI in rats.RH-EPO can suppress ventricular remodeling, through reducing ventricular relative weight and infarct size and promoting the renewal of capillary in infarction area after AMI in rats.