多氯联苯(PCBs)影响多个器官,某些作用是通过干扰调节哺乳动物生理过程的甲状腺激素(TH)信号来介导的。目前尚不清楚多氯联苯如何影响骨骼肌(SM)。在我们的研究中,wistar大鼠注射2,3\',4,4\',5-五氯联苯(PCB118)以0、10、100和1000μg/kg/天腹膜内注射13周,和C2C12成肌细胞处理PCB118(0,0.25,25和50nM)24小时或48小时。我们发现,肌细胞横截面积(MCSA)减少,MyHCIIa和MyHCIIbmRNA水平显著下降,PCB118暴露大鼠的肌肉力量减弱。在体内和体外暴露于PCB118后,TH受体α(TRα)和2型碘甲状腺原氨酸脱碘酶(DIO2)均上调。透射电镜显示在PCB118处理的大鼠中显著的线粒体异常,PCB118暴露后,PTEN诱导的激酶1(PINK1)和GTP酶动力蛋白相关蛋白1(DRP1)等线粒体调节因子的表达发生了改变。这些结果表明,PCB118可以削弱大鼠的肌肉力量,减弱快速抽搐纤维和SM的纤维大小。TH信令,线粒体动力学和线粒体自噬也受到PCB118的干扰,这可能有助于SM结构和功能的改变。
Polychlorinated biphenyls (PCBs) affect multiple organs, and some of the effects are mediated by interfering with thyroid hormone (TH) signaling that regulates physiological processes in mammals. It remains unclear how PCBs affect skeletal muscle (SM). In our study, wistar rats were injected 2,3\',4,4\',5-pentachlorobiphenyl (PCB118) intraperitoneally at 0, 10, 100, and 1000 μg/kg/day for 13 weeks, and C2C12 myoblasts were treated PCB118 (0, 0.25, 25, and 50 nM) for 24 h or 48 h. We found that myocyte cross-sectional area (MCSA) was reduced, MyHC IIa and MyHC IIb mRNA levels significantly decreased, and muscle strength was weakened in PCB118-exposed rats. TH receptor α (TRα) and iodothyronine deiodinase type 2 (DIO2) were upregulated after PCB118 exposure both in vivo and in vitro. Transmission electron microscopy showed significant mitochondrial abnormalities in PCB118-treated rats, and the expression of mitochondrial regulators such as PTEN-induced kinase 1 (PINK1) and GTPase dynamin-related protein 1 (DRP1) were altered after PCB118 exposure. These results suggest that PCB118 could weaken muscle strength and attenuate fast-twitch fibers and fiber size of SM in rats. TH signaling, mitochondrial dynamics and mitophagy were also disturbed by PCB118, which may contribute to the alternations of SM structure and function.