甲状腺功能减退症对成年期SD大鼠肾脏超微结构的影响及L-T4替代治疗的效果

目的 观察甲状腺功能减退症(简称甲减)对成年期 SD大鼠肾脏超微结构的影响及左旋甲状腺素(L-T4)替代治疗的效果.方法 将30只健康3月龄雄性SD大鼠适应性喂养1周,随机均分为对照组、甲减组和L-T4治疗组.通过丙基硫氧嘧啶饮水法建立甲减模型,共6周.从第5周开始,L-T4治疗组大鼠给每日予L-T4腹腔注射(剂量按体质量6 μg/100 g计算);对照组及甲减组每日予同等剂量生理盐水腹腔注射.造模结束后对所有大鼠进行称重,之后使用放射免疫法检测三组大鼠甲状腺功能,同时使用透射电镜完成肾脏超微结构观察.结果 造模前,三组大鼠体质量水平比较差异无统计学意义;造模结束后,对照组、甲减组和L-T4治疗组三组大鼠体质量较造模前各增加了 48. 14％、 22. 18％ 、34. 90％.造模后三组间体质量比较显示:甲减组、 L-T4治疗组大鼠体质量显著低于对照组(P<0. 05);与对照组相比,甲减组大鼠血清甲状腺激素(T3、T4)水平明显降低,促甲状腺素水平显著升高(P<0.01) ,L-T4治疗组血清甲状腺激素及促甲状腺素水平与对照组相比差异无统计学意义;电镜下观察显示对照组大鼠肾小球足细胞结构完整,足突排列清晰,线粒体发达、内部嵴结构清晰;甲减组大鼠肾小球基底膜结构不规则,足细胞明显肿胀、融合,内部细胞器结构不清晰,线粒体明显空泡变性,内部嵴断裂消失,粗面内质网有脱颗粒现象,间质水肿;L-T4治疗组以上超微结构改变明显改善.结论 甲减可致成年期SD大鼠肾脏超微结构发生病理学损害,L-T4替代治疗有利于上述损伤的恢复.

The effects of levothyroxine treatment on ultrastructral changes in kidney of adult hypothyroid rats

Objective To observe the ultrastructural changes in kidney of adult hypothyroid rats and the effects of levothyroxine treatment. Methods 30 male SD rats were randomly divided into three groups: control, hypothyroid and hypothyroid treated with levothyroxine (6 μg/100 g body weight). Hypothyroidism was induced by adding 0. 05％ propylthiouracil to their drinking water for 6 weeks. From the 5th week, hypothyroid rats in the L-T4 therapy group received levothyroxine in saline solution by ip injection daily for 2 weeks (6 μg/100 g body weight). The control and hypothyroid groups were given the saline solution by ip injection daily for 2 weeks. After 6 weeks, the rats were killed for assaying body weight and the thyroid functions, and the ultrastructure of the kidney was observed by transmission electronmicroscope (TEM ). Results There were no significant differences in body weight of rats among the groups before experiment; after the experiment, the body weight in the control group, hypothyroid group and levothyroxine treatment group increased by 48. 14％, 22. 18％ and 34. 90％ respectively. The weights of SD rats in the other groups were significantly lower than that of the control group after experiment (P < 0. 05). The serum T3 and T4 levels were significantly lowerandthyroid stimulating hormone levels were higher (P <0. 01) in SD rats of hyporhyroid group than that in the control. Levothyroxine(L-T4) treatment restored T3, T4 andthyroid stimulating hormone levels, which were not significantly different from the control values. TEM revealed that the ultra-structures of the glomerular podocytes in the control group was complete, the mastectomy was clear, the mitochondria was well developed, and the structure of the internal ridge was clear. The ultrastructures of the hypothyroid rats revealed that the glomerular basement membrane was irregular, the podocytes were greatly swollen and fused, and the internal organelles were not clear, most mitochondria exhibited vacuolar degeneration, the internal ridge fractured, the rough endoplasmic reticulum showed degranulation, and interstitial edema; L-T4 treatment significantly improved the ultrastructural changes mentioned above. Conclusion Adult hypothyroidism can cause pathological alterations of renal ultrastructures in SD rats. Levothyroxine replacement therapy is beneficial to the recovery of the changes.