Rubinger D, Krause Y, Krause I, Popovtzer M M
Nephrology and Hypertension Services, Hadassah University Hospital, Jerusalem, Israel.
Proc Soc Exp Biol Med. 1990 Oct;195(1):13-7. doi: 10.3181/00379727-195-43103.
Previous studies from our laboratory have shown that 24,25(OH)2D3 attenuates the calcemic effect of 1,25(OH)2D3 in rats with reduced renal mass. This study was undertaken to clarify the role of parathyroid hormone in this response. Adult rats (n = 27) with reduced renal mass after parathyroidectomy with an initial plasma calcium of 3.7 +/- 0.1 mEq/liter were divided into four groups: (i) control rats and rats treated with (ii) 24,25(OH)2D3, (iii) 1,25(OH)2D3, and (iv) both 1,25 and 24,25(OH)2D3. After 4 days significant hypercalcemia was seen in PTX animals receiving 1,25(OH)2D3 alone or in combination with 24,25(OH)2D3. Plasma calcium in the combined therapy rats (7.42 +/- 0.22 mEq/liter) was significantly higher than in those treated with 1,25(OH)2D3 alone (6.68 +/- 0.22 mEq/liter, P less than 0.05). After 8 days, plasma calcium was higher in the rats treated with 1,25(OH)2D3 but was of same magnitude in those treated with 1,25(OH)2D3 alone or in combination with 24,25(OH)2D3. In contrast, in a subset of rats (n = 35) with reduced renal mass but intact parathyroid glands similarly treated with the vitamin D metabolites, a blunted calcemic response was seen after the combination of 1,25(OH)2D3 with 25,25(OH)2D3 administration alone. These results show that in rats with reduced renal mass, 24,25(OH)2D3 attenuates the calcemic effect of 1,25(OH)2D3 only in the presence of intact parathyroid glands. The different calcemic responses to 1,25 or combined 1,25 and 24,25(OH)2D3 in intact or parathyroidectomized rats with chronic renal insufficiency may result from different interaction between the vitamin D metabolites and the parathyroid hormone, presumably at the level of bone.
我们实验室之前的研究表明，24,25(OH)₂D₃可减弱肾质量降低的大鼠体内1,25(OH)₂D₃的血钙升高作用。本研究旨在阐明甲状旁腺激素在这一反应中的作用。将成年大鼠（n = 27）在甲状旁腺切除术后肾质量降低，初始血浆钙为3.7±0.1 mEq/升，分为四组：(i) 对照大鼠以及接受(ii) 24,25(OH)₂D₃、(iii) 1,25(OH)₂D₃和(iv) 1,25(OH)₂D₃与24,25(OH)₂D₃联合治疗的大鼠。4天后，单独接受1,25(OH)₂D₃或与24,25(OH)₂D₃联合治疗的甲状旁腺切除动物出现明显的高钙血症。联合治疗组大鼠的血浆钙（7.42±0.22 mEq/升）显著高于单独接受1,25(OH)₂D₃治疗的大鼠（6.68±0.22 mEq/升，P＜0.05）。8天后，接受1,25(OH)₂D₃治疗的大鼠血浆钙更高，但单独接受1,25(OH)₂D₃或与24,25(OH)₂D₃联合治疗大鼠的血浆钙水平相当。相比之下，在另一组肾质量降低但甲状旁腺完整的大鼠（n = 35）中，同样用维生素D代谢物进行治疗，单独给予1,25(OH)₂D₃与24,25(OH)₂D₃联合用药后血钙反应减弱。这些结果表明，在肾质量降低的大鼠中，24,25(OH)₂D₃仅在甲状旁腺完整的情况下减弱1,25(OH)₂D₃的血钙升高作用。在慢性肾功能不全的完整或甲状旁腺切除大鼠中，对1,25(OH)₂D₃或1,25(OH)₂D₃与24,25(OH)₂D₃联合用药的不同血钙反应，可能源于维生素D代谢物与甲状旁腺激素之间不同的相互作用，推测是在骨骼水平上。
