Mizobuchi M, Finch J L, Martin D R, Slatopolsky E
Renal Division, Washington University School of Medicine, St Louis, Missouri 63110, USA.
Kidney Int. 2007 Sep;72(6):709-15. doi: 10.1038/sj.ki.5002406. Epub 2007 Jun 27.
Vascular calcification is associated with cardiovascular disease, the most common cause of death in chronic kidney disease (CKD). Patients with CKD are treated with vitamin D receptor activators (VDRAs); therefore, we determined if this treatment affects vascular calcification. Uremic rats were given vehicle, calcitriol, paricalcitol, or doxercalciferol three times a week for 1 month. Calcitriol significantly increased the serum calcium-phosphate product and aortic calcium content. Paricalcitol had no effect but the same dose of doxercalciferol significantly increased the calcium-phosphate product and the aortic calcium content, the latter being confirmed by von Kossa staining. To see if the increased aortic calcium was due to an increased serum calcium-phosphate product or to a differential effect of the two VDRAs, we lowered the dose of doxercalciferol and increased the dose of paricalcitol. A lower doxercalciferol did not increase the calcium-phosphate product but increased the aortic calcium content. A higher dose of paricalcitol still had no effect. Doxercalciferol treatment increased the mRNA and protein expression of the bone-related markers Runx2 and osteocalcin in the aorta, whereas paricalcitol did not. Hence, different VDRAs have different effects on vascular calcification in uremic rats. The effects are independent of the serum calcium-phosphate product suggesting independent mechanisms.
血管钙化与心血管疾病相关，而心血管疾病是慢性肾脏病（CKD）最常见的死亡原因。CKD患者接受维生素D受体激活剂（VDRAs）治疗；因此，我们确定这种治疗是否会影响血管钙化。给尿毒症大鼠每周三次给予赋形剂、骨化三醇、帕立骨化醇或度骨化醇，持续1个月。骨化三醇显著增加血清钙磷乘积和主动脉钙含量。帕立骨化醇没有效果，但相同剂量的度骨化醇显著增加钙磷乘积和主动脉钙含量，后者经冯·科萨染色证实。为了观察主动脉钙增加是由于血清钙磷乘积增加还是由于两种VDRAs的不同作用，我们降低了度骨化醇的剂量并增加了帕立骨化醇的剂量。较低剂量的度骨化醇没有增加钙磷乘积，但增加了主动脉钙含量。较高剂量的帕立骨化醇仍然没有效果。度骨化醇治疗增加了主动脉中骨相关标志物Runx2和骨钙素的mRNA和蛋白质表达，而帕立骨化醇则没有。因此，不同的VDRAs对尿毒症大鼠的血管钙化有不同的影响。这些影响独立于血清钙磷乘积，提示存在独立的机制。
