甲状腺素对大鼠心肌T型钙通道蛋白和mRNA的影响

目的:观察甲状腺素对大鼠心肌T型钙通道Cav3.1、Cav3.2和Cav3.3表达的影响,探讨T型钙通道表达变化与甲亢性心脏病引起的心律失常之间的关系。方法:选取健康SD大鼠20只,随机分为正常对照组和甲亢性心脏病组(n=10),腹腔注射L-甲状腺素(0.5 mg/kg)连续35 d建立大鼠甲亢性心脏病模型。检测各组大鼠血清T3和T4的含量,测定各组大鼠心脏指数和心肌细胞横径,并行心电图检查;免疫组化和Western blot检测各组大鼠心肌T型钙通道蛋白的表达;RT-PCR检测心肌T型钙通道mRNA的表达。结果:造模35 d后与正常对照组比较,甲亢性心脏病组大鼠血清T3和T4含量明显升高,心脏指数和心肌细胞横径明显增加(P0.05),并发生心律失常;免疫组化、Western blot和RT-PCR结果显示,甲亢性心脏病组大鼠心肌Cav3.1表达较正常对照组明显增加(P0.05),Cav3.2表达明显减少(P0.01),Cav3.3的表达无变化。结论:甲状腺素可促进心肌Cav3.1mRNA和蛋白的表达,抑制Cav3.2 mRNA和蛋白的表达,而对Cav3.3的表达则没有影响。Cav3.1和Cav3.2的表达变化可能与甲亢性心脏病心律失常的发生有关。

Effects of thyroid hormone on myocardial T-type calcium channels at mRNA and protein levels in rats

AIM: To observe the effect of thyroxine on the expression of T-type calcium channels Cav3.1, Cav3.2 and Cav3.3 in rat myocardium, and to explore the possible biological mechanism between the changes of the expression of T-type calcium channels and the arrhythmia in hyperthyroid heart disease. METHODS: Healthy SD rats (n=20) were randomly divided into normal control group (n=10) and hyperthyroid heart disease group (n=10). The animal model was established by intraperitoneal injection of levothyroxine for 35 d. The contents of T3 and T4 in serum, the heart-to-body weight ratio, the diameter of cardiac myocytes and electrocardiograph were measured to evaluate hyperthyroid heart disease. Moreover, the mRNA and protein expression levels of T-type calcium channels in the myocardium were measured by RT-PCR, immunohistochemistry and Western blot. RESULTS: After intraperitoneal injection of levothyroxine for 35 d, compared with the normal control group, the serum contents of T3 and T4, the heart-to-body weight ratio and the diameter of cardiac myocytes were significantly increased in hyperthyroid heart disease group (P<0.05), and arrhythmia occurred in hyperthyroid heart disease group. By immunohistochemistry and Western blot, the protein expression of Cav3.1 increased significantly (P<0.05), while the protein expression of Cav3.2 decreased significantly (P<0.01). However, no change of the Cav3.3 protein was observed. The results of RT-PCR were the same as immunohistochemistry and Western blot. CONCLUSION: Thyroxine promotes the expression of Cav3.1 in the myocardium but inhibits the expression of Cav3.2 at mRNA and protein levels, which might be involved in arrhythmia in hyperthyroid heart disease.