目的 探讨microRNA-146(miR-146)及其靶基因白介素1受体相关激酶(IRAK1)和TNF-α受体相关因子6(TRAF6)在甲亢性心脏病中的调控作用。 方法 60只雄性C57BL/6J小鼠随机分为对照组(Control组,n=30)和甲亢性心脏病实验组(T4组,n=30)。T4组按1 μg/g腹腔注射甲状腺素稀释液,Control组腹腔注射生理盐水150 μL。7周后,麻醉做心电图;ELISA检测血清中TT3及TT4;HE和Masson染色观察心脏形态学改变;RT-qPCR检测miR-146表达;Western blot检测IRAK1及TRAF6表达。 结果 与Control组相比,T4组小鼠心率明显加快,心电图发现异常;血清TT3及TT4升高,P<0.001;心肌细胞结构紊乱,胶原纤维增多;miR-146a及miR-146b表达明显上调,P<0.001;IRAK1及TRAF6蛋白表达明显下调,P<0.001。 结论 miR-146可能通过IRAK1和TRAF6调控甲亢性心脏病。
Abstract
Objective To discuss the effect of miR-146 and its target genes IRAK1 and TRAF6 on regulating of hyperthyroid cardiopathy. Methods Male C57BL/6J mice (n=60) were randomly divided into a Control group (n=30) and a T4 group (n=30). Mice in the T4 group were intraperitoneally injected with T4 diluent (1 μg/g). Mice in the control group were intraperitoneally injected with normal saline (150 mL). After 7 weeks, electrocardiogram was made after anesthetization; ELISA was used to detect serum TT3 and TT4; HE and Masson stain was used to observe the heart morphological change. qPCR was used to detect the expression of miR-146. Western blot was used to detect the protein level of IRAK1 and TRAF6. Results Compared with the Control group, heart rate was significantly increased and electrocardiogram was abnormal in mice of the T4 group; Serum TT3 and TT4 were significantly increased (P<0.001). Cardiomyocytes was disordered in structure and more abundant in collagen fiber; miR-146a and miR-146b were significantly up-regulated, P<0.001; IRAK1 and TRAF6 were significantly down-regulated, P<0.001. Conclusion miR-146 may regulate hyperthyroid cardiopathy by IRAK1 and TRAF6.
关键词
甲亢性心脏病 /
miR-146 /
IRAK1 /
TRAF6
Key words
Hyperthyroid cardiopathy /
microRNA-146 /
IRAK1 /
TRAF6
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基金
国家自然科学基金资助项目(No.81660046);广西自然科学基金(No.2016GXNSFBA380001)