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作 者:刘妍妍[1] 白云龙[1] 王涛[1] 杜娟[1] 张妍[1] 李宝馨[1] 吕延杰[1] 杨宝峰[1]
机构地区:[1]哈尔滨医科大学药理学教研室黑龙江省生物医药重点试验室,黑龙江哈尔滨150086
出 处:《中国药理学通报》2007年第2期181-184,共4页Chinese Pharmacological Bulletin
基 金:国家自然科学基金重点资助项目(No30430780);国家自然科学基金面上资助项目(No30371647)
摘 要:目的研究白藜芦醇(resveratrol,RES)对豚鼠心室肌细胞L型钙通道的影响。方法酶解法分离单个豚鼠心室肌细胞,采用全细胞膜片钳技术记录白藜芦醇对豚鼠单个心室细胞L型钙通道电流(ICa-L)的影响。结果不同浓度的RES明显抑制ICa-L,1、10、100μmol.L-1L的RES使其峰电流密度从(12.96±1.48)pA/pF减少到(11.36±1.59)、(9.96±1.51)和(7.77±0.68)pA/pF(n=6,P<0.01),冲洗后可恢复至(11.85±0.83)pA/pF。RES可使ICa-L的I-U关系曲线上移,其形状和峰值电压保持不变;RES还可使通道的激活曲线右移,但失活曲线和失活恢复时间无改变。结论白藜芦醇通过延长L型钙通道激活过程而明显抑制ICa-L,减少细胞外的钙离子内流,延长有效不应期,从而发挥抗心律失常作用。Aim To investigate effects of different concentrations of resveratrol (RES) on L-type calcium channels in guinea pig ventricular myocytes. Methods Enzyme digestion was used to isolate single ventricular myocyte and whole cell patch clamp technique was used to record L-type calcium current. Results RES inhibited ICa-L in a concentration- dependent manner . The application of 1,10,100 μmol · L^-1 RES reduced the density of peak ICa-L from ( - 12. 96 ± 1.48 ) pAL/ pFto ( - 11.36 ± 1.59)pA/pF (n= 6,P〈0.01), (-9.96±1.51) pA/pF (n= 6, P〈 0.01) and ( -7.77 ±0.68) pA/pF (n = 6,P〈0.01) pA/pF at 0 mV, respectively, ICa-L came back to ( - 11.85± 0. 83) pA/pF after washout. RES remarkably shifted activation curve to the right, and delayed the voltage- dependent steady-state activation of calcium current. The half activation potential ( V1/2 ) was ( - 32. 32801±0.366 ) mV in the control and( - 23. 36414 ± 0. 94711 ) mV in thc presence of RES 1 μmol· L^-1. The slope factor(k) was (8. 86352±0. 37865) in the control and ( 8. 7592 ± 0. 8847 ) in the presence of RES 1 μmol· L^-1 ( n = 6,P 〈 0. 05). Steady-state inactivation curve was not affected markedly, also V1/2 value and k value in the presence of RES 1 μmol·L^-1 were not markedly different from those of the control. The recovery time from inactivation was not changed significantly. Conclusion RES decreased the amplitude of L-type calcium current, which would be one of cardiac protection mechanisms of the drug. And slowing the activation procession of Ica would help to its cardiac protection.
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