兔心房组织L型钙通道表达的增龄性变化及卡托普利的干预作用

Effects of captopril on aging-related changes of L-type Ca^(2+) channel in rabbit atria

目的动态观察家兔心房组织L型钙通道表达的增龄性改变以及血管紧张素转换酶抑制剂卡托普利的干预作用。方法健康家兔按月龄分为成年、老年和老年+卡托普利干预组。药物干预8周后,体表心电图测量P波平均时限和P波离散度;ELISA检测试剂盒测定心房组织血管紧张素Ⅱ(AngⅡ)的含量;real-time PCR技术测定兔左心耳L型电压依赖型钙通道α1C亚单位的mRNA表达;Western blot检测L型钙通道α1C亚单位蛋白表达。结果与成年组相比,老年组的P波平均时限延长,P波离散度增大(P<0.01);心房组织AngⅡ的含量增加(P<0.01);L型钙通道α1C亚单位基因表达明显下调(P<0.01)。与老年组相比,卡托普利干预组P波平均时限以及P波离散度均缩短,心房组织AngⅡ的含量减少(P<0.05);卡托普利干预组L型钙通道α1C亚单位的mRNA及蛋白含量较老年组均上调(P<0.05)。结论心房肌细胞L型钙通道α1C亚单位基因和蛋白表达的增龄改变可能是老年易发房颤的分子机制之一;而卡托普利对这种增龄性改变的逆转作用可能是其防治房颤的潜在机制。

Objective To investigate the aging-related changes of L-type calcium channel（LCC） expression in rabbit atria and to explore the intervention effects of angiotensin-converting enzyme（ACE） inhibitor captopril. Methods Rabbits were divided into three groups ： old group, adult group and old ＋ captopril group （ oral administration of captopril）. After intervention for eight weeks, P wave average duration （PAD） and P wave dispersion （PWD） were measured on 12-lead surface electrocardiography （ EGG）, Ang II level was evaluated by the rabbit Ang 11 ELISA kit, and the mRNA and protein expression of LCC α1 C subunits in the left atria was measured by real-time PCR and Western blot respectively. Results Compared with adult group,PAD,PWD and Ang II level were increased in old group （ P 〈 0.01 ）. RT-PCR and Western blot results showed old rabbits exhibited less LCC α1C subunits expression than the adult ones （P 〈 0.01 ）. Compared with old group, PAD ,PWD and Ang II level decreased in captopril group（P 〈 0.05 ）, but the protein and mRNA expression levels of LCC al C subunits increased （ P 〈 0.05 ）. Conclusion The aging - related changes of mRNA and protein expression of LCC α1 C subunits in rabbit atrial cardiomyocytes may be one of mechanisms of the susceptibility to AF with aging. However, the reverse effect of captopril on the aging - related changes may be the underlying mechanism in the prevention and treatment of AF.