大鼠心房肌增龄性变化对心房颤动发生率及持续时间的影响

Aging-related changes in rats and their effect on the high incidence rate and duration of atrial fibrillation in aged rats

目的：研究大鼠心房肌缝隙连接蛋白Cx40增龄性改变及增龄导致心房颤动发生率增高及房颤持续时间延长的原因。方法：随机取9-12月龄（青年组）、16-19月龄（中年组）、24-26月龄（老年组）健康雄性SD大鼠,每组24只。每组随机取12只通过尾静脉注射乙酰胆碱Ach-氯化钙混合液0.1 m L/100 g诱发房颤,监测其肢体导联心电图,记录各组大鼠房颤发生率及房颤持续时间。每组余下的12只大鼠麻醉后取心房组织,各组心房肌组织分别用苏木素一伊红及马森染色观察心房肌细胞及基质的改变,运用免疫荧光染色结合激光扫描共聚焦成像技术及免疫印迹技术检测Cx40的分布及量的改变。结果：老年组12只大鼠房颤发生率（83.3%,10只）及房颤持续时间均高于其他两组（P〈0.05）,其心房肌细胞肥大,细胞排列稀疏,心肌纤维化明显。Cx40的表达量随增龄显著减少,老年组与青年组比较,差异有统计学意义（P〈0.05）,且缝隙连接蛋白的分布由端端排列为主渐趋杂乱。结论：老年组大鼠心房颤动诱发率较高及房颤持续时间长可能与心房组织形态结构增龄性重构、心房内缝隙连接蛋白Cx 40的数量减少及分布改变相关。

Objective： To investigate the aging-related changes in gap junction protein-connexin 40（ cx40） in rats and their effect on the high incidence rate and duration of atrial fibrillation in aged rats. Methods： The 72 healthy male Sprague-Dawley rats were randomly divided into 3age groups（ n = 24,each）,9- 12 months（ young-adult）,16- 19 months（ middle-adult） and 24- 26 months（ aged）. Atrial fibrillation was induced by injecting mixed Ach-Ca Cl2 solution into the caudal veins of SD rats which are selected randomly,12 rats in each group. The incidence rate and duration of atrial fibrillation was recorded by monitoring their limb-lead Electroa rdiogram（ ECG）. The remaining 12 rats in each group take the atrial tissue after anesthesia,morphological changes of atrial myocardium were observed under optical microscope in Hematoxylin（ HE） and Masson＇s stain. The Cx40 protein expression was assessed by Western-Blot and the distribution of Cx40 was observed by confocal immunofluorescence microscopy. Results： The incidence rate（ 83%,n =10） and duration of atrial fibrillation was much higher and longer in aged group than in other two groups（ all P〈0. 05）,and the aged group showed that atrial muscle cells were enlarged,the cells arranged sparse,and the myocardial fibrosis was obvious. The expression amount of Cx40 decreased as age increased compared with the young-adult,the difference was statistically significant（ P〈0. 05）,and the distribution of Cx40 changed from end-to-end to disordered arrangement. Conclusion： For aged rats,the high incidence rate and long duration of atrial fibrillation may be associated with atrial myocardium reconstruction,disarrangement of gap junction proteins and decreased expression amount of Cx40.