螺内酯对高甲状腺素诱导的兔心房颤动和心房重构的影响

Effect of spironolactone on hyperthyroxine-induced atrial fibrillation and atrial remodeling in and rabbits

目的:探讨螺内酯对高甲状腺素诱导的兔心房颤动(AF)和心房重构的影响。方法:新西兰兔33只随机分为3组:正常对照组(C)、高甲状腺素组(H)和螺内酯组(S)。H和S组腹腔注射甲状腺素4周建立兔甲亢性AF模型,之后,S组给予螺内酯灌胃2周。给药结束后,通过心内电生理高频刺激诱发AF,计算AF诱发率,测量心房有效不应期(AERP)。荧光定量PCR测定L型钙通道亚基(Cav1.2)、钾通道相关亚基(Kv1.5、Kv4.3)和缝隙连接蛋白(Cx40、Cx43)的mRNA表达,Western blot和免疫组化测定上述指标的蛋白表达。结果:螺内酯降低AF诱发率。H组和S组的AERP无明显差异(P>0.05)。S组Cav1.2蛋白表达水平明显高于H组(P<0.05)。S组Kv1.5的mRNA和蛋白表达水平均明显低于H组(P<0.05),S组Kv4.3的蛋白表达水平显著低于H组(P<0.05)。S组Cx43的mRNA表达水平明显低于H组(P<0.01),S组Cx40的蛋白表达水平显著低于H组(P<0.05)。结论:螺内酯可降低高甲状腺素所致的AF诱发率,改善其引起的心房重构。

AIM： To detect the effect of spironolactone on hyperthyroxine-induced atrial remodeling. METHODS： New Zealand rabbits were divided into control group（ C）,hyperthyroxine group（ H） and spironolactone group（ S）. Thyroxin was given to the rabbits in group H and group S by intraperitoneal injection for 4 weeks,and then spironolactone was given in group S by gavage for 2 weeks. Atrial fibrillation（ AF） was induced by ＂ burst＂ stimulation after administration. The inducing rate of AF and atrial effective refractory period（ AERP） were tested by intra-cardiac electrophysiologic instrument. The expression of AF-related Ca2 ＋channel（ Cav1. 2）,K＋channels（ Kv1. 5 and Kv4. 3） and connexins（ Cx40 and Cx43） at mRNA and protein levels was detected by real-time PCR,immunohistochemistry and Western blot. RESULTS： Spironolactone reduced the inducing rate of AF. No significant difference of AERP between group H and group S was observed（P〈0. 05）. Compared with group H,the protein expression of Cav1. 2 was significant increased in group S（P〈0. 05）. The expression of Kv1. 5 at mRNA and protein levels in group S was significantly lower than that in group H（P〈0. 05）,while the protein expression of Kv4. 3 in group S was significantly decreased compared with group H（P〈0. 05）. The mRNA expression of Cx43 in group S was significantly decreased compared with group H（P〈0. 01）,whereas the protein expression of Cx40 in group H was significantly higher than that in group S（P〈0. 05）. CONCLUSION： Spironolactone attenuates the hyperthyroxine-induced atrial remodeling in rabbits,and reduces the susceptibility of the myocardium to AF.