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[摘要]
目的 研究薯蓣皂苷含药血清对正常大鼠心室肌细胞钠离子通道电流(INa)的影响,探讨其保护心肌细胞及抗心律失常的离子机制。方法 大鼠ig给予300 mg/kg薯蓣皂苷,2次/d,连续4 d,末次给药后1 h从腹主动脉取血,离心分离得含药血清;采用酶解法分离大鼠单个心室肌细胞,以全细胞膜片钳技术记录薯蓣皂苷含药血清低、中、高剂量(1、10、100 μL)分别对大鼠正常心室肌细胞INa的影响。结果 薯蓣皂苷含药血清1、10、100 μL均使I-V曲线下移,内向电流增加;1 μL薯蓣皂苷含药血清使INa峰值增大,而10、100 μL的薯蓣皂苷含药血清使INa峰值由(-52.10±3.80)pA/pF变为(-76.44±4.09)pA/pF和(-81.96±4.70)pA/pF(P<0.01),呈剂量依赖性。1、10、100 μL薯蓣皂苷含药血清剂量依赖性加速钠离子通道激活过程,半数稳态激活电压分别由(-57.69±1.86)mV变为(-59.71±2.57)、(-66.56±1.32)(P<0.01)、(-68.52±3.91)mV(P<0.01),但对失活过程无明显影响。1、10、100 μL薯蓣皂苷含药血清剂量依赖性加速钠离子通道的复活过程,拟合复活曲线τ值由(150.73±21.49)ms分别变为(143.19±13.88)、(84.83±18.03)(P<0.01)、(80.63±13.89)ms(P<0.01)。结论 薯蓣皂苷含药血清通过加快激活过程及复活过程促进钠离子的内流。
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[Abstract]
Objective To investigate the effects of serum containing dioscin on sodium current (INa) and reveal the mechanisms of cardioprotection and antiarrhymias. Methods Serum was obtained from the aortaventralis from Wistar rats after ig administration 4 d of dioscin 300 mg/kg, twice daily for 4 d. Single ventricular myocytes were isolated from adult rat hearts by enzymatic dissociation and the effects of dioscin on INa were observed by whole-cell patch clamp. Results Serum containing dioscin shifted downward the I-V curve with increased peak current density. With the effects of 1, 10, and 100 μL serum containing dioscin, the peak current density was dose-dependently changed from (-52.10 ± 3.80) pA/pF to (-76.44 ± 4.09) pA/pF and (-81.96 ± 4.70) pA/pF, respectively (P < 0.01 vs control); Dioscin facilitated the activation process with the inactivation process unchanged. The half activation potential was changed from (-57.69 ± 1.86) mV to (-59.71 ± 2.57) mV, ( -66.56 ± 1.32) mV (P < 0.01 vs control), and (-68.52 ± 3.91) mV (P < 0.01 vs control), respectively; The recovery process of sodium channel was accelerated by 1, 10, and 100 μL serum containing dioscin with the recovery constant τ changed from (150.73 ± 21.49) ms to (143.19 ± 13.88) ms, (84.83 ± 18.03) ms (P < 0.01 vs control), and (80.63 ± 13.89) ms (P < 0.01 vs control). Conclusion Serum containing dioscin could increase the sodium current by facilitating the activation process and accelerating the recovery process of sodium channel.
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[基金项目]
天津医科大学科学基金资助项目(2011ky35);黑龙江省自然科学基金资助项目(D2007-104)