摘要
目的 观察不同年龄段家兔心房组织细胞缝隙连接蛋白表达的增龄性变化及ACEI类药物卡托普利对其干预作用.方法健康家兔按月龄分为青年组(4~6月)、老年组(30~34月)、老龄+卡托普利干预组,每组8只.药物干预8周后,测量各组家兔体表心电图P波时限、P波离散度等电生理指标;采用血管紧张素Ⅱ(Ang-Ⅱ)ELISA检测试剂盒测定心房组织AngⅡ的含量;用实时定量逆转录聚合酶链反应(RT-PCR)法测定家兔左心耳Cx40、Cx43的mRNA表达,用Western blot检测其蛋白表达.结果 ①与青年组相比,体表心电图测定结果显示老年组家兔心率明显下降(P〈0.01),P波的Pmax、Pmin、Pd和Pa均显著延长(P均〈0.01).②与青年组相比,老年组心房组织AngⅡ浓度升高;Cx40、Cx43 mRNA及蛋白的表达均下降(P〈0.01).③与老年组相比,卡托普利干预组,心率增快,反应P波的各指标均有明显的恢复(P均〈0.05);Cx40、Cx43 mRNA及蛋白的表达均有所回升(〈0.05).结论 增龄导致Pd及Pa增加有利于房颤的发生;增龄造成Cx40、Cx43表达下降可能是增龄性房颤发生的分子机制;而卡托普利对其的逆转作用可能是其预防房颤发生的潜在机制之一.
Objective To observe the expression of connexins of atrial myocardium that increases with age and investigate the therapeutic effects of captopril on age-related changes. Methods Healthy rabbits were divided into three groups with 8 in each group: adult (4--6 months), old (30--34 months) and old+captopril. After 8 weeks of intervention, eletrophysiological markers P wave average duration (Pa) and P wave dispersion (Pd) were recorded in each group. Cardiac angiotensin (Ang) ]/ levels were assessed by a commercial ELISA kit. The expressions of Cx43 and Cx40, the two atrial connexins, were analyzed at the mRNA and protein levels by real-time PCR and Western blot in the left atrial appendages from rabbits of both groups. Results (D The ECG result of the old rabbits manifested longer Pa and Pd than those of the adult ones (both P〈0.01). (~) Ang ]] accumulation was higher in the old group than in the young group (P〈0.01). The gene and protein levels of Cx40 and Cx43 expressions decreased in the atrium of old rabbits compared with the adults (P〈0.01). (3) Compared with those in the old group, the Pd and Pa in the captopril group were all significantly shorter (P〈0.05). Captopril increased the mRNA and protein expressions of Cx40 and Cx43 in the old rabbits (〈 0.05). Conclusion Aging markedly prolongates Pa and Pd of atria, which predicts the development of AF. The age-related decrease of gene and protein expressions of Cx40 and Cx43 may be the molecular mechanism of AF due to aging. CaptopriI's reversing the age- associated changes may contribute to preventing AF.
出处
《西安交通大学学报(医学版)》
CAS
CSCD
北大核心
2014年第2期231-234,共4页
Journal of Xi’an Jiaotong University(Medical Sciences)
基金
国家自然科学基金资助项目(No.39870333)~~