【摘要】 目的研究甲状腺素对犬心房电生理特征和连接蛋白connexin43表达及分布的影响,探讨甲状腺功能亢进性心脏病(甲亢性心脏病)发生房颤的机制。方法健康成年杂种犬16只,随机分为对照组(n=6)和实验组(n=10)。给实验组犬腹腔注射左旋甲状腺素(L-thy)80μg/(kg.d),持续8个月,以建立犬甲亢动物模型,分别于0、2、4、6和8个月测定心房有效不应期(AERP),Western blot检测心房连接蛋白connexin43表达,激光共聚焦显微镜观察connex-in43表达及分布的改变。结果和对照组相比,L-thy组犬第4、6、8个月AERP明显缩短(P<0.05),左、右心房con-nexin43表达显著下降(P<0.01),两组左心房connexin43表达量的差值显著高于两组右心房connexin43表达量的差值(P<0.05),左、右心房分布于细胞两端的connexin43显著减少(P<0.01)。结论甲状腺激素导致的心房电重构和连接蛋白的重构是甲状腺激素所致心房重构过程的一部分,参与促成了甲亢性心脏病房颤的发生、发展及维持。更多还原

【Abstract】 Objective To determine potential alterations in electrophysiological proterties of atrial tissue and the expression distribution of connexin43 in dog with hyperthyroidism induced by Levothyroxine(L-thy).MethodsSixteen mongrel canines weighing 12～17 kg were randomized into control group(n=6) and L-thy group(n=10).L-thy(80 μg/kg) was administered daily by intraperitoneal injection for 8 months to all dogs in the L-thy group.Every 2 months atrial effective refractory period(AERP) was measured in both groups.Atrial tissues were collected at the 8th month.The expression of connexin43 in atria was measured with western blot analysis.Connexin43 in atria was identified with tissue localization by immunofluorescence and laser scanning confocal microscope.ResultsCompared with the control group,AERP of the L-thy group in the 4th,6th and 8th month was significantly shorter(P<0.05).Levothyroxine significantly reduced the expression of connexin43 in left and right atrial(P<0.01),and the heterogeneous connexin43 down-regulation between left and right atria in the L-thy group was significant(P<0.05).Cx43 located at the intercalated disc of atrial myocardium in the L-thy group was significantly reduced(P<0.01).ConclusionThyroid hormone leads to atrial electrical remodeling and gap junction remodeling,involving heterogeneous reduction in connexin43 expression and disturbance in the distribution of con-nexin43.These changes are components of a variety of remodeling processes necessary,although not causative,for atrial fibrillation(AF) to become sustained.更多还原