碘缺乏致甲状腺功能减退症大鼠肾脏损害的病理特点分析  

Pathological characteristics of renal damage in rats with hypothyroidism caused by iodine deficiency

作　　者：张靖[1] 高天舒[2] 范秋灵[3] 

机构地区：[1]中国医科大学附属第一医院内分泌科,沈阳110001 [2]中国医科大学附属第一医院肾内科,沈阳110001 [3]辽宁中医药大学附属医院内分泌科,沈阳110001

出　　处：《中华内分泌代谢杂志》2012年第11期922-926,共5页Chinese Journal of Endocrinology and Metabolism

基　　金：教育部博士点基金（20092133110004）,辽宁省教育厅（2009A492）,辽宁省教育厅优秀人才计划（LR201026）

摘　　要：目的观察大鼠甲状腺功能减退时肾脏病理形态及血管内皮生长因子（VEGF）的改变。方法将大鼠随机（随机数字表法）分为正常组及实验组，实验组随机分为模型组、左旋甲状腺素（L—T4）组，实验组建立碘缺乏甲减肾损害大鼠模型，21d成模时及用药56d后测定甲状腺功能（TT3、TT4及TSH）、血肌酐、血尿素氮（BUN）水平；光镜观察肾脏形态，免疫组化检测VEGF表达水平。结果（1）用药56d后与正常对照组相比L．Td组及模型组BUN均增高[（5．55±0．50，5．80±0．66对5．00±0．24）mmol／L，P〈0．05]，血肌酐也均增高[（26．83±0．75，27．0±3．41对22．5±2．07）μmol／L，P〈0．05]，L—T。组略低于模型组，但无统计学意义。（2）PAS染色比较：21d成模时，模型组肾小球部分区域系膜细胞增生，系膜区扩大，系膜基质增多。用药56d后模型组整个肾小球轻至中度系膜增生，增生的系膜细胞连成片，毛细血管开放数量减少，可见明显扩张的毛细血管。L-T4组系膜增生较模型组明显减轻，毛细血管开放数量增多，仍可见毛细血管扩张。（3）肾脏VEGF蛋白表达：21d成模时模型组VEGF积分光密度（IODA）明显高于正常组（44．64±14．99对29．05±9．14，P〈0．01）。用药56d时与正常组比各组IODA均无明显差异，L-T4组略高于模型组，但无统计学意义。结论碘缺乏致甲减肾损害病理改变特点为系膜增生．肾毛细血管床减少和毛细血管扩张。VEGF在甲减肾损害的不同病程中表达不同，早期升高，后期下降。L-T4治疗未能逆转甲减肾损害大鼠的肾功能异常。Objective To study the renal pathology and expression of vascular endothelial growth factor （VEGF） in rats with hypothyroidism caused by iodine deficiency. Methods The rats were randomly grouped into test group and normal group, and the test group was further randomly divided into model group and L-T4 group. Observation were made when the hypothyroid model was formed after maneuvering for 21 days and the medication had been taken for 56 days. The observed data included the morphogy of the kidney, serum TT3, TT4 , TSH, blood urea nitrogen （BUN） , serum creatinine （SCr） , and VEGF expression. Results （ 1 ） After medication for 56 days, compared to normal group, BUN and SCr levels in L-T4and model groups showed apparently increasing [ BUN（5.55 ±.50, 5.80 ±.66 vs 5.00±0.24 ） mmol/L, P〈0. 05 ; SCr（ 26.83 ±0.75,27.0 ±3.41 vs 22.5 ±2.07 ） p, moL/L, P〈0.05 ], and L-T4 group showed slightly lowered BUN and SCr levels compared with model group （ P〉0.05 ）. （2） By 21 days, in the model group there was moderate mesangial hyperplasia involving focal glomeruli. By 56th day of medication, entire glomeruli showed moderate mesangial hyperplasia with lessened number of dilated capillaries in the model group. However, in the L-T4 treated group, mesangial hyperplasia was much less and capillaries though dilated appeared wholesome, as compared with the model group. （ 3 ） By 21 th day, the IODA value of VEGF in the model group was higher than that in the normal control（44.64 ± 14.99 vs 29.05± 9.14, P〈0. 01 ）. After medication for 56 days, there was no significant difference in the IODA value of three groups. Conclusions The characteristics of renal pathology in rats with hypothyroidism caused by iodine deficiency consist of mesangial hyperplasia and loss of glomerular capillaries. The expression of VEGF is raised early in the course of renal damage, but lowered thereafter. L-T4 can not reverse the sustained kidney damage and impaired renal function.

关 键 词：甲状腺功能减退症 肾脏损害 血管内皮生长因子 

分 类 号：R581.2[医药卫生—内分泌]