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目的 本研究应用新型的非肽类血管紧张素Ⅱ (ANGⅡ )受体拮抗剂CV1 1 974,特异性地阻断ANGⅡ受体(AT1 ) ,观察它对培养心肌细胞活力的影响 ,旨在探讨心肌细胞功能下降的细胞机理 ,为临床正确应用ANGⅡ受体拮抗剂提供实验依据。方法 本研究利用培养的乳鼠心肌细胞 ,根据活细胞线粒体在能量代谢过程中可作用于甲基噻唑基四唑 (MTT)产生蓝紫色结晶产物 (formazan)这一原理 ,应用比色法测定ANGⅡ对培养心肌细胞的活力的影响和CV1 1 974的干预作用。结果 :ANGⅡ在 1 2h之内使formazan产物的OD值逐渐上升 ,1 2h达到高峰 ,此后开始下降 ,至 2 4h已低于正常水平 ,它们的OD值之间均差异有极显著性意义 (P <0 .0 1 ) ,CV1 1 974可以显著地拮抗ANGⅡ对心肌细胞活力的影响 ,应用CV1 1 974后所有时相点MTT产物的OD值之间差异无显著性意义 ,(P >0 .0 5)。结论 该结果提示ANGⅡ在早期具有提高心肌细胞活力的效应 ,CV1 1 974可以显著地拮抗ANGⅡ对心肌细胞活力的影响。这一发现对了解ANGⅡ在心功能不全代偿和心衰发生中的作用及临床如何恰当使用ANGⅡ受体拮抗剂具有重要参考价值
In this study, a new non-peptide angiotensin Ⅱ (ANGⅡ) receptor antagonist, CV1 1 974, was used to block the angiotensin Ⅱ receptor (AT1) specifically and to observe its effect on the viability of cultured cardiomyocytes. Cell function decreased cell mechanism for the clinical application of angiotensin receptor antagonist ANG provide an experimental basis. Methods In this study, cultured neonatal rat cardiomyocytes were used to detect the formation of ANGZIN by colorimetric method according to the principle that mitochondria of live cells can act on the formation of blue-purple formazan in methyl thiazolyl tetrazolium (MTT) during energy metabolism. On the vitality of cultured cardiomyocytes and CV1 1 974 intervention. RESULTS: ANGⅡ increased the OD value of formazan product within 12 h, reached the peak at 12 h, then decreased and reached a level below 24 h after ANGI, and the OD values of them were significantly different (P <0.01). CV1 1 974 could significantly antagonize the effect of ANGⅡ on the viability of cardiomyocytes. There was no significant difference in OD values of MTT products at all time points after application of CV1 1 974 (P> 0.05) 5). Conclusions The results suggest that ANGⅡ has the effect of increasing cardiomyocyte activity in the early stage. CV1 1 974 can significantly antagonize the effect of ANG Ⅱ on cardiomyocyte viability. This finding is of great value to understand the role of angiotensin Ⅱ in the occurrence of heart failure and heart failure, and how to use angiotensin receptor antagonist