血清甲状腺激素浓度与肾病大鼠GHIGF轴紊乱及生长障碍的关系

目的 :探讨营养不良、肾病本身和糖皮质激素作为各自独立因素对大鼠血清甲状激素浓度的影响 ,阐明甲状腺激素浓度的改变与肾病 (ＮＳ)大鼠生长激素 胰岛素样生长因子 (ＧＨ ＩＧＦ)轴紊乱及生长障碍的关系。方法 :2 4只周龄相同体重相近的雄性ＳＤ大鼠被随机分成正常、食物对照、阿霉素 (5ｍｇ·ｋｇ- 1 )肾病 (肾病组 )和地塞米松 (1 8ｍｇ- 1 ·ｄ- 1 )治疗的阿霉素肾病 (治疗组 )四组。血清Ｔ3 /Ｔ4,ＧＨ ,ＩＧＦ Ｉ浓度采用放射免疫法检测 ,胰岛素样生长因子结合蛋白 (ＩＧＦＢＰｓ)浓度采用Ｗｅｓｔｅｒｎｌｉｇａｎｄｂｌｏｔ法检测 ,肝脏生长激素受体 (ＧＨＲ),ＩＧＦ Ｉ/ＩＧＦＢＰｓｍＲＮＡ表达分别采用放射受体分析和ＲＴ ＰＣＲ法检测。结果 :①除食物对照组大鼠血清Ｔ4呈增高趋势外 ,血清甲状腺激素 (Ｔ3 和Ｔ4)浓度按正常、食物对照、肾病和治疗组顺序逐一减低 ;②相关与分组分析均显示血清甲状腺激素浓度大鼠肝脏ＧＨＲ ,ＩＧＦ Ｉ/ＩＧＦ ＢＰ 3ｍＲＮＡ表达和血清ＴＧＦ Ｉ/ＩＧＦＢＰ 3浓度呈正相关 ,与血清ＩＧＦＢＰ 2浓度呈负相关 ;③血清甲状腺激素浓度与大鼠鼻 尾长度和体重均呈正相关 (均Ｐ <0 . 0 1 )。结论 :甲状腺激素减低可能是肾病综合征血清Ｉ

Relationship between serum thyroid hormone and GH IGF axis, growth failure in nephrotic rats

Objective To investigate the individual effects of malnutrition, nephrosis and glucocorticoid therapy on serum thyroid hormone, and explore the relationship between serum thyroid hormone and GH IGF axis, growth failure in nephrotic rats. Methods Twenty four male Sprague Dawley (SD) rats were randomly divided into control group, pair fed group, doxorubincin induced nephrotic group (nephrotic group) and dexamethasone treated nephrotic group (des treated group). Serum T 3/T 4, GH and IGF I were measured by RIA, serum IGFBPs were measured by Western ligand blot, liver GHR and IGF I/IGFBPs mRNA were analyzed by radioreceptor assay and RT PCR respectively. Results ①Serum thyroid hormone was low in pair fed group, lower in nephrotic group and lowest in des treated group except for high serum T 4 in pair fed group. ②Serum thyroid hormone was positively related with liver GHR, IGF I/IGFBP 3 mRNA and serum IGF I/IGFBP 3, and negatively related with serum IGFBP 2. ③Serum thyroid hormone was positively related with nose tail length and weight (both P<0.01). Conclusions The hypothyroidism is a possible mechanism of reducing serum IGF I levels and biologic action, and resulting in growth failure in nephrotic syndrome.