中国药理学与毒理学杂志
中國藥理學與毒理學雜誌
중국약이학여독이학잡지
CHINESE JOURNAL OF PHARMACOLOGY AND TOXICOLOGY
2006年
6期
448-454
,共7页
苗庆峰%苏素文%张伟%郭鸣放%李林芳%孟静%张永健
苗慶峰%囌素文%張偉%郭鳴放%李林芳%孟靜%張永健
묘경봉%소소문%장위%곽명방%리림방%맹정%장영건
抗心律失常药%双苯氟嗪%心律失常%心肌%钙细胞内
抗心律失常藥%雙苯氟嗪%心律失常%心肌%鈣細胞內
항심률실상약%쌍분불진%심률실상%심기%개세포내
anti-arrhythmia agents%dipfluzine%arrhythmia%myocardium%calcium,cytosolic
目的 观察双苯氟嗪对实验性心律失常的作用及其可能机制.方法 采用静脉灌流毒毛花苷G诱发豚鼠心律失常,心肌缺血再灌注诱发大鼠心律失常,观察双苯氟嗪的抗心律失常作用;利用激光共聚焦扫描显微镜观察双苯氟嗪对心室肌细胞内游离钙子浓度([Ca2+]I)的影响.结果 双苯氟嗪20 mg·kg-1能提高毒毛花苷G诱发豚鼠室性早搏、室速、室颤和死亡的剂量;10 mg·kg-1提高诱发室性早搏的剂量.双苯氟嗪20 mg·kg-1减少心肌缺血再灌注诱发的大鼠室速、室颤发生率及动物死亡率;10 mg·kg-1减少室颤发生率及动物死亡率.双苯氟嗪预先给药可降低豚鼠正常心室肌细胞[Ca2+]I,并抑制细胞外高钙诱发的细胞[Ca2+]I升高;在细胞外高钙已诱发细胞[Ca2+]I升高的条件下,仍可降低[Ca2+]I升高的程度.结论 双苯氟嗪具有抗实验性心律失常作用,这种作用可能与其保持细胞内钙稳态有关.
目的 觀察雙苯氟嗪對實驗性心律失常的作用及其可能機製.方法 採用靜脈灌流毒毛花苷G誘髮豚鼠心律失常,心肌缺血再灌註誘髮大鼠心律失常,觀察雙苯氟嗪的抗心律失常作用;利用激光共聚焦掃描顯微鏡觀察雙苯氟嗪對心室肌細胞內遊離鈣子濃度([Ca2+]I)的影響.結果 雙苯氟嗪20 mg·kg-1能提高毒毛花苷G誘髮豚鼠室性早搏、室速、室顫和死亡的劑量;10 mg·kg-1提高誘髮室性早搏的劑量.雙苯氟嗪20 mg·kg-1減少心肌缺血再灌註誘髮的大鼠室速、室顫髮生率及動物死亡率;10 mg·kg-1減少室顫髮生率及動物死亡率.雙苯氟嗪預先給藥可降低豚鼠正常心室肌細胞[Ca2+]I,併抑製細胞外高鈣誘髮的細胞[Ca2+]I升高;在細胞外高鈣已誘髮細胞[Ca2+]I升高的條件下,仍可降低[Ca2+]I升高的程度.結論 雙苯氟嗪具有抗實驗性心律失常作用,這種作用可能與其保持細胞內鈣穩態有關.
목적 관찰쌍분불진대실험성심률실상적작용급기가능궤제.방법 채용정맥관류독모화감G유발돈서심률실상,심기결혈재관주유발대서심률실상,관찰쌍분불진적항심률실상작용;이용격광공취초소묘현미경관찰쌍분불진대심실기세포내유리개자농도([Ca2+]I)적영향.결과 쌍분불진20 mg·kg-1능제고독모화감G유발돈서실성조박、실속、실전화사망적제량;10 mg·kg-1제고유발실성조박적제량.쌍분불진20 mg·kg-1감소심기결혈재관주유발적대서실속、실전발생솔급동물사망솔;10 mg·kg-1감소실전발생솔급동물사망솔.쌍분불진예선급약가강저돈서정상심실기세포[Ca2+]I,병억제세포외고개유발적세포[Ca2+]I승고;재세포외고개이유발세포[Ca2+]I승고적조건하,잉가강저[Ca2+]I승고적정도.결론 쌍분불진구유항실험성심률실상작용,저충작용가능여기보지세포내개은태유관.
AIM To investigate whether dipfluzine (Dip) possesses antiarrhythmic effect on experimental arrhythmias and effect on cytosolic calcium in ventricular myocytes of guinea-pig. METHODS Experimental arrhythmias were induced by strophanthin G infusion through jugular vein in guinea-pigs and by myocardial ischemia-reperfusion (I-R) in rats respectively. Cytosolic calcium concentration ([Ca2+]i) of isolated guinea-pig ventricular myocytes was examined with laser confocal scanning microscope. RESULTSIn guinea-pigs pretreatment with Dip 20 mg·kg-1 increased the dosages of strophanthin G required to induce ventricular premature contraction (VP), ventricular tachycardia (VT), ventricular fibrillation (VF) and cardiac arrest (CA), pretreatment with Dip 10 mg·kg-1 increased the dosages of strophanthin G required to induce VP. In the I-R-induced arrhythmic model of rats, Dip 20 mg·kg-1 decreased the number of rats exhibiting VT, VF and CA, and the number of rats exhibiting VF and CA was decreased by Dip 10 mg·kg-1. Both Dip and verapamil (Ver) decreased [Ca2+]i of the ventricular myocytes in normal Tyrode′s solution. The Ca2+ overload evoked by high extracellular Ca2+ levels was inhibited by Dip and Ver, and the prophylactic effect of Dip was less than that of Ver, while the curative effect of Dip was more obvious than that of Ver. CONCLUSION Dip has antiarrhythmic effect, which is likely related to the modulation on the intracellular calcium homeostasis.