甲状腺激素减少对大鼠肾脏解耦联蛋白-2表达的影响

Study on the expression of uncoupling protein 2 in the kidney of the rats with hypothyroidism

目的 观察甲状腺激素减少时肾脏线粒体解耦联蛋白-2（UCP2）表达的改变,探讨甲状腺激素减少时肾脏损伤的发生机制. 方法 按随机数字表法将Wistar大鼠分为对照组和甲状腺激素减少组（甲减组）,每组10只.采用低碘饮食复制甲状腺功能减退大鼠模型,对照组摄碘量10.00 μg/d,甲减组1.24 μg/d,两组均适应喂养1周,条件饲养3个月后取血测定甲状腺功能指标,取肾脏组织,用免疫组化法及逆转录-聚合酶链反应（RT-PCR）测定UCP2的蛋白及mRNA表达. 结果 与对照组比较,甲减组促甲状腺激素（TSH,mU/L）明显上升（4.88±1.37比1.65±0.33,P〈0.05）,三碘甲状腺原氨酸总量（TT3）、甲状腺素总量（TT4）、游离三碘甲状腺原氨酸（FT3）、游离甲状腺素（FT4）均明显下降[TT3（nmol/L）：0.54±0.07比0.98±0.17;TT4（nmol/L）：7.82±2.18比48.78±3.65;FT3（pmol/L）：2.28±0.22比2.99±0.10;FT4（pmol/L）：11.38±1.74比29.27±0.95,均P〈0.01].免疫组化显示,甲减组UCP2蛋白在肾小球和肾小管中的表达均低于对照组（肾小球：0.17±0.02比0.24±0.04,肾小管：0.19±0.02比0.25±0.02,均P〈0.01）.RT-PCR显示,甲减组UCP2 mRNA表达明显低于对照组（0.70±0.19比1.30±0.09,P〈0.01）. 结论 甲状腺激素减少时肾脏中UCP2表达下调,提示可能会有损伤肾脏,其机制与肾脏线粒体UCP2表达下调有关.

：Objective To observe the change in the expression of uncoupling protein 2（UCP2） in kidney mitochondria in rats with hypothyroidism,and study the mechanism of renal injury due to hypothyroidism. Methods The Wistar rats were randomly divided into control group（n=10） and hypothyroidism group（n=10）.The hypothyroidism rat model was reproduced by low-iodine diet.The intake of iodine in control group and hypothyroidism group were 10.00 μg/d and 1.24 μg/d,respectively.The rats were raised under these conditions respectively for 3 months after they adapted to the feeding for 1 week.Then the thyroid function parameters were measured in blood,and the expressions of UCP2 protein and mRNA in renal tissue were measured by immunohistochemistry and reverse transcription-polymerase chain reaction（RT-PCR） methods. Results The thyrotropic-stimulating hormone（TSH,mU/L） in hypothyroidism group was significantly higher than that in control group（4.88±1.37 vs.1.65±0.33,P〈0.05）.The levels of total triiodothyronine（TT3）,total thyroxine（TT4）,free triiodothyronine（FT3） and free thyroxine（FT4） in serum in hypothyroidism group were significantly lower than those in control group[TT3（nmol/L）：0.54±0.07 vs.0.98±0.17,TT4（nmol/L）：7.82±2.18 vs.48.78±3.65,FT3（pmol/L）：2.28±0.22 vs.2.99±0.10,FT4（pmol/L）：11.38±1.74 vs.29.27±0.95,all P〈0.01].The immunoh-istochemistry study revealed that the UCP2 protein expression in both renal glomeruli and tubule tissues in the hypothyroidism group was significantly lower than that of control group（renal glomeruli：0.17±0.02 vs.0.24±0.04,renal tubule：0.19±0.02 vs.0.25±0.02,both P〈0.01）.The RT-PCR showed that the UCP2 mRNA expression in the hypothyroidism group was significantly lower than that of control group（0.70±0.19 vs.1.30±0.09,P〈0.01）. Conclusion Hypothyroidism may produce damage to kidney,which is related to the down-regulation of UCP2 expression in the mitochondria of renal cells.