高血磷对慢性肾衰竭大鼠血管钙化的影响

目的 研究高血磷对慢性肾衰竭大鼠血管钙化的影响。 方法 44只Wistar雄性大鼠分别行5/6肾切除（n=24，模型组）或假手术（n=20，对照组），39只大鼠术后4周开始给予高磷或低磷饮食10周。动物分4组：模型组+高磷饮食(CHP)，模型组+低磷饮食(CLP)，对照组+高磷饮食(NHP)，对照组+低磷饮食(NLP)。高磷饮食配方：磷（P）1.2%, 钙（Ca）1.6%，维生素D 1 IU/kg；低磷饮食配方：P 0.2%, Ca 0.5%，维生素D 1 IU/kg。特定饮食开始（基线）和结束时称体质量；检测Scr、血P、血Ca、1,25(OH)2D3、全段甲状旁腺激素（iPTH）。特定饮食结束时处死大鼠，取胸主动脉组织，采用Von Kossa染色和钙含量测定判断血管钙化程度，同时检测核心结合因子α1（Cbfα-1）mRNA的表达。 结果 术后第4周特定饮食开始时，模型组大鼠Scr水平显著高于对照组大鼠 （94.4±17.6）比（36.4±0.6）μmol/L，P < 0.05]，余各项指标组间差异无统计学意义。特定饮食10周时，4组间体质量差异无统计学意义；各组各时间点血Ca水平差异均无统计学意义；血1,25(OH)2D3水平除了在NLP组显著增高外，余3组间差异均无统计学意义；CHP组血P和iPTH水平显著增高，出现严重血管钙化、程度3～4级；胸主动脉钙含量明显增高，同时Cbfa-1 mRNA表达显著上调。血P水平对胸主动脉钙含量的影响比iPTH水平更强（β ＝ 0.832>0.267）。血P水平与胸主动脉钙含量、Cbfα-1 mRNA表达量呈直线正相关（r = 0.672～0.73，P < 0.05）。 结论 高血磷是导致慢性肾衰竭大鼠血管钙化的重要因素。 Cbfα-1的表达上调可能是其导致血管钙化的机制之一。

Influence of hyperphosphatemia on vascular calcification in chronic renal failure rat

Objective To study the influence of hyperphosphatemia on vascular calcification in chronic renal failure(CRF) rats. Methods Male Wistar rats (n=44) underwent 5/6 nephrectomy (n=24, model rats) or sham operation(n=20, control rats). From the 4th week after 5/6 nephrectomy, thirty nine rats were fed with high phosphorous (HP) diet diet formular: phosphate (P) 1.2%, calcium (Ca) 1.6% and Vitamin D 1 IU/kg] or low phosphorous (LP) diet (diet formular: P 0.2%, Ca 0.5% and Vitamin D 1 IU/kg) for 10 weeks respectively. They were divided into four groups as follows: (1) CRF rats receiving HP diet (CHP group), (2) CRF rats receiving LP diet (CLP group), (3) control rats receiving HP (NHP group), (4) control rats receiving LP (NLP group). At the 4th week (baseline) and 14th week (end point), serum creatimine (Scr), serum Ca, serum P, serum 1,25(OH)2D3, intact parathyroid hormone (iPTH) and body weight were examined. At the 14th week, thoracic aorta was removed. Calcification were confirmed in the upper and lower part of aorta by Von Kossa staining and measurerment of calcium content. The middle part was frozen for measurement of core binding factor α-1 (Cbfα-1) mRNA by real-time PCR. Results At the 4th week (baseline), there were no significant differences of serum Ca, 1,25(OH)2D3, serum P,iPTH and body weight among 4 groups. Scr level in CRF rats was significantly higher than that in control rats (P<0.05). At the 14th week , there were no significant differences of Ca and body weight among 4 groups. 1,25（OH)2D3 level was slightly increased in CLP group compared to baseline(P=0.048), whereas no significant difference was found among other 3 groups. At the 14th week, Scr level in CRF rats was significantly higher than that in control rats (P<0.05). Serum P and iPTH levels increased significantly in CHP group compared with baseline (P<0.05).Vascular calcification was found in CHP group. with significant increase in calcium content of the aorta and Cbfα-1 expression as compared to any other groups（P<0.05）. There was a stronger relationship between serum P and calcium content than iPTH and calcium content (Beta:0.832>0.267). Serum P level had a linear positive correlation with calcium content and quantity of Cbfα-1 mRNA（r=0.672~0.73，P<0.05）. Conclusion Hyperphosphatemia is an important factor to influence vascular calcification in chronic renal failure rats, possibly through up-regulation of Cbfα-1.