因宁片对甲亢性肝损害大鼠肝脏的甲状腺激素受体和Ⅰ型脱碘酶基因表达的影响

目的研究因宁片对甲亢性肝损害大鼠的肝组织内甲状腺激素受体(TR)和Ⅰ型脱碘酶(DioⅠ)基因表达的影响。方法采用L-甲状腺激素钠(800 g kg-1 d-1)灌胃建立大鼠甲亢性肝损害模型。给予因宁片低(0.6 g.kg 1.d 1)、中(1.2g.kg 1.d 1)、高(2.4 g.kg 1.d 1)剂量、甲亢灵(1.2 g.kg 1.d 1),灌胃给药30 d后,处死大鼠。取部分肝脏通过实时荧光定量PCR方法检测肝组织中TR 1、TR 2、TR 1、DioⅠ基因的表达变化,酶联免疫吸附法(Elisa)法检测肝组织中DioⅠ含量,Chapra氏方法测定肝组织DioⅠ的活性。结果与空白对照组比较,模型组TR 1表达上调,TR 2表达下调,TR 1表达上调(P<0.01);因宁片能抑制TR 1和TR 1基因表达(P<0.05),对TR 2表达影响不明显(P>0.05)。模型组DioⅠ表达与空白对照组相比显著增强(P<0.01),含量增加(P<0.01)、活性升高(P<0.05);与模型组比较,因宁片能显著降低DioⅠ表达,并呈剂量依赖趋势(r=0.792,P<0.01),各剂量组均降低DioⅠ含量(P<0.05或P<0.01),因宁片中、高剂量能显著降低DioⅠ活性(P<0.05)。结论肝组织内TR和DioⅠ表达异常,可能参与甲亢性肝损害的发生。因宁片能调节甲亢性肝损害大鼠肝脏的TR和DioⅠ基因的异常表达、降低DioⅠ含量、抑制DioⅠ的活性,这可能是因宁片治疗甲亢性肝损害的分子作用机制之一。

Effect of Yinning Tablet on Gene Expressions of Thyroid Hormone Receptor and Type I Iodothyronine Deiodinase in Liver Tissues of Rat with Hyperthyroidism Liver Damage

OBJECTIVE To investigate the effect of Yinning tablet on gene expressions of thyroid hormone receptor （TR） and type I iodothyronine deiodinase （Dio I ） and activity of Dio I in liver tissues of rat with hyperthyroidism liver damage. METHODS Rats were perfused intragastrically with Levothyroxine sodium tablets（800 μg·kg-1·d-1） to establish the rat model of hyperthyroidism-induced liver injury. Rats were treated with Yinning tablets at 0.6, 1.2, 2.4 g·kg-1·d-1 and Jiakangling at 1.2 g·kg-1·d-1 for 30 days, respectively. After treatment, liver samples were immediately collected. The levels of gene expressions of TRα1, TRα2, TRD1 and Dio I in liver tissues were determined by real-time quantitative PCR, meanwhile, the Dio I level was detected with enzyme-linked immunosorbent assay, and the activity of Dio I was tested with Chopra＇s method. RESULTS Compared with control group, the mRNA expressions of TRα1 and TRβ1 were up-regulated and the expression of TRα2 was down-regulated（P〈0.01）, the content and activity of Dio I were increased（P〈0.01 or P〈0.05）. Yinning tablet inhibited the the expressions of TRα1 and TRα1 genes（P〈0.05）, but no statistical difference was noted on the expression of TRα2（P〉0.05）. Compared with the control group, the level of gene expression and activity of Dio I in model group was significantly increased（P〈0.01, P〈0.05）. Compared with the model group, Yinning tablet significantly inhibited mRNA expression of Dio ] in a dose-dependent（r=-0.792, P〈0.01） way. Yinning tablet in different dosage groups could decrease the level of Dio I （P〈0.05, P〈0.01）, Yinning tablet in medium and high groups could significantly reduce Dio I activity（P〈0.05）. CONCLUSION TR and Dio I expression in liver tissue might be involved in the occurrence of Hyperthyroidism liver damage. Yinning tablet may adjust the expressions of TR and Dio I genes and inhibit the content and activity of Dio I in liver tissues of rat with Hyperthyroidism liver damage, which may be one of the molecular action mechanisms through which Yinning tablet prevents Hyperthyroidism liver damage.