罗格列酮对四氧嘧啶介导的糖尿病家兔心室肌细胞L型钙通道电流的影响

Influence of rosiglitazone on L-type calcium ionic current of ventricular myocytes in healthy and diabetic rabbits

目的探讨罗格列酮对家兔心室肌细胞L型钙通道电流(I_(CaL))的影响。方法四氧嘧啶建立糖尿病家兔模型后,利用酶解法急性分离心室肌细胞,用全细胞膜片钳技术观测糖尿病和罗格列酮对心肌细胞I_(CaL)的影响,并与正常家兔进行比较。结果 (1)正常组家兔心室肌细胞I_(CaL)电流密度[(-8.83±2.31)pA/pF]大于糖尿病组[(-8.84±1.98)pA/pF],但差异不具有统计学意义。(2)给予罗格列酮后正常和糖尿病家兔组心室肌细胞I_(CaL)[正常组:基线电流密度(-8.83±2.31 pA/pF)大于5 min电流密度(-4.17±1.89 pA/pF)和10 min电流密度(-5.54±1.63)pA/pF,糖尿病组:基线电流密度(-8.84±1.98)pA/pF大于5 ml‘n电流密度(-4.97±1.15)pA/pF和10 min电流密度(-3.89±1.06)pA/pF],各时段差异均有统计学意义(各组P<0.05)。(3)空腹血糖[(7.65±1.60)mmol/L]小于建模48 h[(17.72±9.15)mmol/L]及1周后空腹血糖[(20.84±9.48)mmol/L]。各时段胰岛素水平[空腹(23.45±9.22)mmol/L,48 h后(22.69±8.94)mmol/L,1周后(21.65±11.91)mmol/L]差异均无统计学意义(各组P>0.05)。结论正常家兔组I_(CaL)电流密度与糖尿病家兔组相似,提示糖尿病对心肌细胞I_(CaL)无明显影响;罗格列酮对心脏的作用不依赖于高血糖存在与否,提示罗格列酮可能通过某些与胰岛素水平有关的特定机制作用于心肌细胞;四氧嘧啶所致糖尿病模型是一种不完全等同于1型及2型糖尿病的独特模型,但去除了胰岛素抵抗的影响。该模型可以用来作为高血糖对心肌细胞离子通道影响的研究载体。

Objective To study the effects of rosiglitazone on L-type calcium ionic current （ICaL ） of ventricular myocytes in healthy and diabetic rabbits. Methods Adult rabbits were randomly divided into normal control group and mesoxalylurea induced diabetes group. Single cardiac myocytes were isolated from ventricles of the rabbits in both groups. Whole cell voltage patch clamp protocol was used to record calcium ionic current. Results There was no significant difference of lcaL at baseline between control group and diabetes group （ -8. 83 ±2. 31 pA/pF vs -8. 84 ＋ 1.98 pA/pF, P 〉 0. 05）. ICaL in control group and diabetes group at 5 min and 10 rain after administration of rosiglitazone were -4. 17 ± 1.89 pA/pF vs - 4.97 ± 1.15 pA/pF, and - 5.54 ± 1.63 pA/pF vs - 3.89 ± 1.06 pA/pF, respectively （ all P 〈 0. 05 ）. Conclusions Diabetes has no significant effect on ICaL of ventricular myocyte in rabbit. Rosiglitazone can decrease ICaL of ventricular myocyte in rabbit, with diabetes or without.