目的探讨咪达普利对舒张性心力衰竭(DHF)大鼠心房肌细胞L型钙通道电流(Ica-L)和Ica-L相关基因Cavl.2蛋白表达的影响。方法30只雄性SD大鼠随机分为对照组、DHF组、低、中、高剂量组,每组6只。后4组采用腹主动脉缩窄建立DHF模型,对照组和DHF组予等量生理盐水,低、中、高剂量组依次给予咪达普利1.5、3和6mg/(kg·d)干预。各组干预4周后,采用心脏超声检测心功能,急性酶解法获得单个大鼠心房肌细胞和标准全细胞膜片钳技术记录通道电流,凝胶电泳法记录心房肌细胞Ica-L相关基因Cavl.2的蛋白表达。结果与对照组比较,DHF组大鼠心房肌细胞Ica-L电流密度峰值和Cavl.2蛋白表达明显减少;与DHF组比较,低、中、高剂量组大鼠心房肌细胞Ica-L峰值电流密度和Cavl.2蛋白表达明显增加,该作用随着咪达普利剂量增加而增加。结论咪达普利明显抑制DHF大鼠心房肌Ica-L下调,此作用与增加心房肌Cavl.2蛋白表达水平有关。
Objective To study the effect of imidapril on L-type calcium current(Ica_L) and expres- sion of Cavl. 2 protein in atrial myocytes of rats with diastolic heart failure(DHF). Methods Thirty male SD rats were randomly divided into control group, DHF group, low imidapril dose group,middle imidapril dose group and high imidapril dose group(6 in each group). A DHF model was established by abdominal aortic coarctation. The rats in low, middle and high imidapril dose groups were treated with imidapril at the doses of 1.5,3 and 6 mg/(kg · d). Their cardiac func- tion was assessed by echocardiography,single atrial myoeytes were isolated by enzymatic dissocia- tion and Ica-L was measured using the whole cell patch clamp technique, expression of Cavl. 2 in atrial myocytes was detected by Western blot. Results The peak density of atrial Ica-L was signifi- cantly lower in DHF group than in control group, which increased in DHF group with the increas- ing dose of imidapril. The expression level of Cavl. 2 protein in atrial myocytes was significantly lower in DHF group than in control group, which increased in DHF group with the increasing dose of imidapril. Conclusion Imidapril can significantly inhibit the peak density of atrial Ica-L in DHF rats by increasing the Cavl. 2 protein expression level in atrial myocytes.