国际中医中药杂志
國際中醫中藥雜誌
국제중의중약잡지
INTERNATIONAL JOURNAL OF TRIDITIONAL CHINESE MEDICINE
2015年
6期
517-523
,共7页
余丞浩%于友华%孙明杰%石晓路
餘丞浩%于友華%孫明傑%石曉路
여승호%우우화%손명걸%석효로
肌细胞,心脏%钙%中草药%乌头碱%大鼠%新乌头碱%次乌头碱
肌細胞,心髒%鈣%中草藥%烏頭堿%大鼠%新烏頭堿%次烏頭堿
기세포,심장%개%중초약%오두감%대서%신오두감%차오두감
Calcium%Myocytes,cardiac%Drugs,Chinese herbal%Aconitine%Rats%Mesaconitine%Hypaconitine
目的：探讨乌头碱、新乌头碱、次乌头碱对心肌细胞钙释放的影响。方法分离的成年Sprague-Dawley大鼠左心室心肌细胞分别使用0.3、1、3μmol/L乌头碱、新乌头碱、次乌头碱溶液灌流12 min，灌流后4、8、12 min时检测自发性钙释放(SCR)诱发率以及舒张末期钙浓度(F0)、钙瞬变幅度(ΔF)的变化。检测灌流0.3μmol/L乌头碱、新乌头碱、次乌头碱溶液后12 min，心肌细胞发挥正性肌力作用时钙瞬变和收缩功能动力学指标的变化。结果乌头碱、新乌头碱、次乌头碱均可诱发SCR，0.3μmol/L时新乌头碱SCR诱发率最高，3μmol/L时乌头碱SCR诱发率最高。与对照组比较，给药后12 min，3μmol/L乌头碱、新乌头碱、次乌头碱均可增加 F0[(1.459±0.379)、(1.585±0.493)、(1.213±0.254)比(1.079±0.108)]、ΔF[(1.615±0.455)、(2.210±0.756)、(1.528±0.422)比(1.036±0.125)]，差异有统计学意义(P均＜0.05)；且新乌头碱ΔF高于乌头碱和次乌头碱(P均＜0.05)。与对照组比较，0.3μmol/L乌头碱、新乌头碱、次乌头碱均可增加ΔF[(0.409±0.127)、(0.423±0.107)、(0.414±0.118)比(0.260±0.065)；P＜0.05或P＜0.01]、收缩幅度[(5.464±2.239)%、(7.449±2.548)%、(5.524±1.645)%比(3.428±0.911)%；P＜0.05或 P＜0.01]，延长钙瞬变达峰时间[(0.041±0.016)s、(0.039±0.009)s、(0.038±0.011)s 比(0.032±0.007)s；P＜0.05或P＜0.01]；与乌头碱组比较，新乌头碱和次乌头碱可降低钙瞬变消除时间常数[(0.301±0.054)s、(0.324±0.064)s 比(0.361±0.076)s；P＜0.05或P＜0.01]，缩短舒张期收缩恢复至50%时的时间[(0.124±0.035)s、(0.126±0.040)s 比(0.157±0.056)s；P＜0.05或 P＜0.01]。结论乌头碱、新乌头碱、次乌头碱的正性肌力作用与毒性效应同时存在，表明心肌细胞内钙浓度升高是产生正性肌力作用的有利因素，也是诱发SCR的危险因素。
目的：探討烏頭堿、新烏頭堿、次烏頭堿對心肌細胞鈣釋放的影響。方法分離的成年Sprague-Dawley大鼠左心室心肌細胞分彆使用0.3、1、3μmol/L烏頭堿、新烏頭堿、次烏頭堿溶液灌流12 min，灌流後4、8、12 min時檢測自髮性鈣釋放(SCR)誘髮率以及舒張末期鈣濃度(F0)、鈣瞬變幅度(ΔF)的變化。檢測灌流0.3μmol/L烏頭堿、新烏頭堿、次烏頭堿溶液後12 min，心肌細胞髮揮正性肌力作用時鈣瞬變和收縮功能動力學指標的變化。結果烏頭堿、新烏頭堿、次烏頭堿均可誘髮SCR，0.3μmol/L時新烏頭堿SCR誘髮率最高，3μmol/L時烏頭堿SCR誘髮率最高。與對照組比較，給藥後12 min，3μmol/L烏頭堿、新烏頭堿、次烏頭堿均可增加 F0[(1.459±0.379)、(1.585±0.493)、(1.213±0.254)比(1.079±0.108)]、ΔF[(1.615±0.455)、(2.210±0.756)、(1.528±0.422)比(1.036±0.125)]，差異有統計學意義(P均＜0.05)；且新烏頭堿ΔF高于烏頭堿和次烏頭堿(P均＜0.05)。與對照組比較，0.3μmol/L烏頭堿、新烏頭堿、次烏頭堿均可增加ΔF[(0.409±0.127)、(0.423±0.107)、(0.414±0.118)比(0.260±0.065)；P＜0.05或P＜0.01]、收縮幅度[(5.464±2.239)%、(7.449±2.548)%、(5.524±1.645)%比(3.428±0.911)%；P＜0.05或 P＜0.01]，延長鈣瞬變達峰時間[(0.041±0.016)s、(0.039±0.009)s、(0.038±0.011)s 比(0.032±0.007)s；P＜0.05或P＜0.01]；與烏頭堿組比較，新烏頭堿和次烏頭堿可降低鈣瞬變消除時間常數[(0.301±0.054)s、(0.324±0.064)s 比(0.361±0.076)s；P＜0.05或P＜0.01]，縮短舒張期收縮恢複至50%時的時間[(0.124±0.035)s、(0.126±0.040)s 比(0.157±0.056)s；P＜0.05或 P＜0.01]。結論烏頭堿、新烏頭堿、次烏頭堿的正性肌力作用與毒性效應同時存在，錶明心肌細胞內鈣濃度升高是產生正性肌力作用的有利因素，也是誘髮SCR的危險因素。
목적：탐토오두감、신오두감、차오두감대심기세포개석방적영향。방법분리적성년Sprague-Dawley대서좌심실심기세포분별사용0.3、1、3μmol/L오두감、신오두감、차오두감용액관류12 min，관류후4、8、12 min시검측자발성개석방(SCR)유발솔이급서장말기개농도(F0)、개순변폭도(ΔF)적변화。검측관류0.3μmol/L오두감、신오두감、차오두감용액후12 min，심기세포발휘정성기력작용시개순변화수축공능동역학지표적변화。결과오두감、신오두감、차오두감균가유발SCR，0.3μmol/L시신오두감SCR유발솔최고，3μmol/L시오두감SCR유발솔최고。여대조조비교，급약후12 min，3μmol/L오두감、신오두감、차오두감균가증가 F0[(1.459±0.379)、(1.585±0.493)、(1.213±0.254)비(1.079±0.108)]、ΔF[(1.615±0.455)、(2.210±0.756)、(1.528±0.422)비(1.036±0.125)]，차이유통계학의의(P균＜0.05)；차신오두감ΔF고우오두감화차오두감(P균＜0.05)。여대조조비교，0.3μmol/L오두감、신오두감、차오두감균가증가ΔF[(0.409±0.127)、(0.423±0.107)、(0.414±0.118)비(0.260±0.065)；P＜0.05혹P＜0.01]、수축폭도[(5.464±2.239)%、(7.449±2.548)%、(5.524±1.645)%비(3.428±0.911)%；P＜0.05혹 P＜0.01]，연장개순변체봉시간[(0.041±0.016)s、(0.039±0.009)s、(0.038±0.011)s 비(0.032±0.007)s；P＜0.05혹P＜0.01]；여오두감조비교，신오두감화차오두감가강저개순변소제시간상수[(0.301±0.054)s、(0.324±0.064)s 비(0.361±0.076)s；P＜0.05혹P＜0.01]，축단서장기수축회복지50%시적시간[(0.124±0.035)s、(0.126±0.040)s 비(0.157±0.056)s；P＜0.05혹 P＜0.01]。결론오두감、신오두감、차오두감적정성기력작용여독성효응동시존재，표명심기세포내개농도승고시산생정성기력작용적유리인소，야시유발SCR적위험인소。
ObjectiveTo investigate the effects of aconitine, mesaconitine and hypaconitine on calcium release in isolated adult rat cardiac myocytes.MethodsThe left ventricular cardiac myocytes isolated from adult Sprague-Dawley rats were perfused withacnitine, mesaconitine and hypaconitine at 0.3 μmol/L, 1μmol/L, 3 μmol/L for 12 min. The spontaneous calcium release (SCR) rate, the end-diastolic[Ca2+](F0) and the calcium transient amplitude (ΔF) were detected 4 min, 8 min and 12 min after the perfusion. 12 min after the perfusion with acnitine, mesaconitine and hypaconitine at 0.3 μmol/L, the changes of systolic dynamics and calcium transient were detected for the positive inotropic effect. Results Any of aconitine, mesaconitine and hypaconitine induced SCR, mesconitine-induced SCR rate was highest at low concentration (0.3 μmol/L), and aconitine-induced SCR rate highest at high concentration (3 μmol/L). Compared with the control, 12 min after the perfusion with acnitine, mesaconitine and hypaconitine at 3 μmol/L elevated F0 (1.459 ± 0.379, 1.585 ± 0.493, 1.213 ± 0.254vs.1.079 ± 0.108, allP<0.05) and ΔF(1.615 ± 0.455, 2.210 ± 0.756, 1.528 ± 0.422vs. 1.036 ± 0.125, allP<0.05), mesaconitine with ΔF higher than aconitine and hypaconitine. At low concentration (0.3 μmol/L), compared with control, aconitine, mesaconitine and hypaconitine increased ΔF (0.409 ± 0.127, 0.423 ± 0.107, 0.414 ± 0.118vs.0.260 ± 0.065;P<0.05 orP<0.01) and contraction amplitudes (5.464% ± 2.239%, 7.449% ± 2.548%, 5.524% ± 1.645%vs.3.428% ± 0.911%;P<0.05 orP<0.01), prolonged the time to peak of calcium transient (0.041 ± 0.016 s, 0.039 ± 0.009 s, 0.038 ± 0.011 svs.0.032 ± 0.007 s;P<0.05 or P<0.01); compared with aconitine, mesaconitine and hypaconitine decreased calcium transient time constant (0.301 ± 0.054 s, 0.324 ± 0.064 svs.0.361 ± 0.076 s;P<0.05 orP<0.01) and diastolic t50 (0.124 ± 0.035 s, 0.126 ± 0.040 svs.0.157 ± 0.056 s;P<0.05 orP<0.01).ConclusionsAconitine, mesaconitine and hypaconitine reveal the positive inotropic effects couple with the toxic effects. Increased[Ca2+]in cardiac myocytes is the key factor for the positive inotropic effects, but also the risk factor for SCR.
