阿托伐他汀对大鼠模拟缺血左室心肌细胞瞬时外向钾电流的作用

Effects of atorvastatin on transient outward potassium of the simulated ischemia myocytes in rat left ventricle

目的观察在单细胞水平,阿托伐他汀对大鼠模拟缺血左室心肌细胞瞬时外向钾电流(Ito)的作用。方法 Wistar大鼠32只,酶解获取左室心肌细胞,随机分4组:对照组(正常Ito外液)、他汀组(正常Ito外液+5μmol/L阿托伐他汀)、缺血组(缺血Ito外液)和缺血加他汀组(缺血Ito外液+5μmol/L阿托伐他汀)。采用全细胞膜片钳记录各组正常外液中的基础Ito,灌流不同电极外液,记录灌流后5～20 min的Ito。结果①标准化Ito峰值(测试电位+50 mV):对照组灌流前后无变化;与基础水平比,灌流5 min时,他汀组、缺血组和缺血加他汀组分别减小13.60%±5.74%、17.94%±3.18%和21.87%±4.36%(均P<0.01),三组间两两比较互无差异;灌流5 min后,他汀组和缺血组继续减小;②门控参数:与基础水平比,灌流5 min时,他汀组半激活电压(V1/2,a)增加5.70%±2.43%(P=0.001),半失活电压(V1/2,i)增加16.32%±13.41%(P=0.034);缺血组和缺血加他汀组V1/2,a分别减小6.95%±3.13%和12.56%±5.75%(均P<0.01),V1/2,i分别减小31.80%±14.06%和36.66%±15.52%(均P<0.01),缺血组和缺血加他汀组之间V1/2,a和V1/2,i均无差异,而分别与他汀组比较时,V1/2,a和V1/2,i均存在差异。结论①阿托伐他汀可能有一定的Ito阻滞样作用,并呈时间依赖性减轻;②模拟缺血20 min内Ito持续减小;③5μmol/L阿托伐他汀不影响模拟缺血20 min内的Ito;④阿托伐他汀和模拟缺血对Ito的V1/2,a和V1/2,i作用方向相反。

Objective To observe the effects of atorvastatin on transient outward potassium （ Ito ） of the normal and simulated ischemia myocytes in rat left ventricle. Methods Thirty-two Wistar rats were used for isolating left ventricular myocytes, which were randomly divided into four groups： control group （normal solution）, atorvastatin group （normal with 5 μmol/L atorvastatin）, ischemia group （simulated ischemia solution） and ischemia-atorvastatin group （simulated ischemia with 5 μmol/L atorvastatin）. Ito was recorded in normal condition （basic state） by whole-cell patchelamp, and was recorded at 5,10,15 and 20 rain after perfusion. Results a. Normalized currents （at 50 mV ）, compared with basic state, there were no significant differences in control group after perfusion, while in atorvastatin group, ischemia group and ischemia-atorvastatin group, when perfused 5 rain, the currents were decreased by 13.60% ± 5.74%, 17.94% ± 3.18% and 21.87% ±4.36% （ all P 〈0.01 ）, and there were no differences among the three groups, and Ito was continuously decreased in atorvastatin group and ischemia group, b. Gate parameters, compared with basic state, when perfused 5 min, in atorvastatin group, the membrane potential at 50% maximal activation （V1/2,a ） increased by 5.70% ± 2.43% （P = 0. 001 ） , and the membrane potential at 50% maximal inactivation （ V1/2,i ） increased by 16.32% ± 13.41% （ P = 0.001 ） ,while in ischemia group and ischemia-atorvastatin group, V1/2,a decreased by 6.95% ± 3.13% and 12.56% ± 5. 75% （ all P 〈0.01 ） , and V1/2,idecreased by 31.80% ±14.06% and 36.66% ±15.52% （ all P〈0.01）; for V1/2,a and Vl/2,i, there were no differences between ischemia group and ischemia-atorvastatin group, but both were significant differences when compared with atorvastatin group respectively. Conclusions a. Atorvastatin plays a time dependent role like potassium channel block in rat left ventricular myocytes, b. During twenty minutes of simulated ischemia, Ito is continuously decreased, c. There is no effects of 5 μmol/L atorvastatin on Ito in the state of simulated ischemia within twenty minutes, d. The effects of atorvastatin and simulated ischemia on V1/2,a and V1/2,i of Ito are conversed.