Szabo A, Merke J, Hügel U, Mall G, Stoeppler M, Ritz E
Department of Internal Medicine, Ruperto Carola University, Heidelberg, Germany.
Eur J Clin Invest. 1991 Oct;21(5):512-20. doi: 10.1111/j.1365-2362.1991.tb01403.x.
Clinical evidence points to disturbed calcium metabolism in lead (Pb) intoxication. To further clarify the mechanisms involved, serum levels of 1,25(OH)2D3, receptors for 1,25(OH)2D3 as well as size and ultrastructure of parathyroid glands were examined in Wistar Kyoto rats exposed to 1% lead (Pb) acetate in drinking water for 10 weeks (short-term study) or 0.001-1% Pb acetate for 24 weeks (long-term study). After administration of Pb for 10 weeks, bone Pb was significantly increased (641 +/- 66.9 (SD) vs. 0.648 +/- 0.39 mg kg-1 ash in controls). Total serum calcium and ionized Ca2+ (1.15 +/- 0.031 vs. 1.25 +/- 0.03 mmol l-1) were significantly decreased. Renal function (Ccr) was unchanged, but urinary cAMP excretion and circulating 1,25(OH)2D3 (177 +/- 10.9 vs. 232 +/- 18.9 pmol l-1) were diminished. Specific binding of 1,25(OH)2D3 was increased in parathyroids (Bmax 128 +/- 4.7 vs. 108 +/- 0.6 fmol mg-1 protein) and intestinal muscosa; Bmax failed to adequately rise in response to pretreatment with 1,25(OH)2D3 (2 x 10 ng day-1 for 4 d) in Pb-exposed animals. Receptor characteristics (sedimentation constant, KD, DNA affinity) were unchanged. Parathyroid weight was significantly increased (178 +/- 25 vs. 96 +/- 34 micrograms) with no change of estimated nuclear volume, cell volume or cell ultrastructure. After 24 weeks of Pb exposure, a dose-dependent but non-linear increase of parathyroid weight was noted between 0.001% and 1% Pb in drinking fluid. The present study documents secondary hyperparathyroidism associated with, and presumably caused by, hypocalcaemia and low 1,25(OH)2D3 levels, in experimental Pb intoxication.
临床证据表明铅（Pb）中毒时钙代谢紊乱。为进一步阐明其中的机制，对饮用含1%醋酸铅的水10周（短期研究）或饮用含0.001 - 1%醋酸铅的水24周（长期研究）的Wistar Kyoto大鼠，检测了血清1,25(OH)₂D₃水平、1,25(OH)₂D₃受体以及甲状旁腺的大小和超微结构。给予铅10周后，骨铅显著增加（641±66.9（标准差），而对照组为0.648±0.39 mg/kg灰分）。总血清钙和离子化Ca²⁺（1.15±0.031对1.25±0.03 mmol/L）显著降低。肾功能（肌酐清除率）未改变，但尿cAMP排泄和循环1,25(OH)₂D₃（177±10.9对232±18.9 pmol/L）减少。甲状旁腺和肠黏膜中1,25(OH)₂D₃的特异性结合增加（最大结合容量Bmax为128±4.7对108±0.6 fmol/mg蛋白）；在铅暴露动物中，经1,25(OH)₂D₃（2×10 ng/天，共4天）预处理后，Bmax未能充分升高。受体特性（沉降常数、解离常数KD、DNA亲和力）未改变。甲状旁腺重量显著增加（178±25对96±34微克），估计的核体积、细胞体积或细胞超微结构无变化。铅暴露24周后，在饮水中铅含量为0.001%至1%之间，甲状旁腺重量呈剂量依赖性但非线性增加。本研究证明在实验性铅中毒中，继发性甲状旁腺功能亢进与低钙血症和低1,25(OH)₂D₃水平相关，且可能由其引起。
