中国血液净化

中国血液净化 ›› 2012, Vol. 11 ›› Issue (05): 263-267.doi: 10.3969/j.issn.1671-4091.2012.05.00

• 基础研究 • 上一篇    下一篇

硫代硫酸钠对高磷诱导的残肾大鼠血管钙化早期干预作用的观察

余 毅 黄 恬   

  1. 福建医科大学福州总医院临床医学院(南京军区福州总医院)血液净化科
  • 收稿日期:2012-02-13 修回日期:1900-01-01 出版日期:2012-05-12 发布日期:2012-05-12
  • 通讯作者: 余毅 yuyicn@126.com
  • 基金资助:

    福建省科技计划重点项目(No.2009Y0040)

Early intervention on high phosphorous induced vascular calcification by sodium thiosulfate administration in rats with remnant kidney

YU Yi, HUANG Tian.   

  • Received:2012-02-13 Revised:1900-01-01 Online:2012-05-12 Published:2012-05-12

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摘要： 【摘要】目的 探讨硫代硫酸钠对高磷诱导的残肾大鼠血管钙化的早期干预作用。方法 5/6肾切除大鼠，术后给予高磷或正常磷饮食16周，以高磷饮食制作血管钙化模型。分为5组：假手术+正常磷组(SNP，n=7)，假手术+高磷组(SHP，n=7)，残肾+正常磷组(NNP，n=7)，残肾+高磷组(NHP，n=7)，残肾+高磷+硫代硫酸钠治疗组(THP，n=7），治疗组以硫代硫酸钠腹腔注射16周。收集尿量检测24h尿蛋白，取血检测血清钙、磷、肌酐、尿素氮。取胸主动脉，HE和von kossa染色检测血管钙化，免疫组化分析大鼠胸主动脉III型钠磷转运体亚型(Pit-1)、核心结合因子(Cbfα1)的表达。结果 各组大鼠尿蛋白、尿素氮、肌酐、尿酸和血磷浓度均有明显差别(F值分别为19.057、43,527、26.688、40.324和7.676,P值均＜0.01)，NHP组较其他各组明显增高(P＜0.05)。HE和von kossa染色显示，NHP组大鼠主动脉呈现明显钙化，SNP、SHP和NNP3组未见明显钙化。免疫组化显示，主动脉Pit-1和Cbfα1表达各组有明显差异（F值为8.259和5.91,P＜0.01)，其中NHP组表达明显增高(P＜ 0.01)，Pit-1和Cbfα1阳性面积比与血磷相关性分析显示分别为：r=0.344，P＜0.05和r=0.376，P＜0.05，Pit-1、Cbfα1表达与血磷呈正相关。THP组血清肌酐、尿素氮、尿酸、血磷和尿蛋白均较NHP组明显下降(P＜0.01或＜0.05)，其主动脉Pit-1和Cbfα1表达明显减少(P＜0.05)，主动脉钙化部分减轻。结论 高磷饮食喂食残肾大鼠，可成功制作血管钙化模型，硫代硫酸钠早期干预，可明显改善其肾功能，降低血磷，下调动脉Pit-1和Cbfα1表达，减轻血管钙化。

关键词: 血管钙化, 磷, 残肾大鼠, 硫代硫酸钠

Abstract: 【Abstract】 Objective To observe the early effect of sodium thiosulfate (STS) on the progression of high phosphorous induced vascular calcification in remnant kidney rats.  Methods  SD rats underwent 5/6 nephrectomy or sham operation. The rats were then fed with high phosphorous or normal diet for 16 weeks. They were divided into 5 groups: (1) rats with sham operation and receiving normal phosphorous diet (SNP, n=7), (2) rats with sham operation rats receiving high phosphorous diet (SHP, n=7), (3) remnant kidney rats receiving normal phosphorous diet (NNP, n=7), (4) remnant kidney rats receiving high phosphorous diet (NHP, n=7), and (5) remnant kidney rats receiving high phosphorous diet and STS (THP, n=7). STS was given intraperitoneally three times a week for 16 weeks. At the 16th week, serum creatinine, urea nitrogen, uric acid, calcium and phosphorus were measured, and thoracic aorta was removed. Vessels were examined for calcification by HE and von kossa staining, and for the expression of Pit-1 and Cbfα1 by immunohistochemistry.  Results  After 16 weeks, urine protein, and serum urea nitrogen, creatinine, uric acid and phosphorus levels were significantly different among the 5 groups (F=19.057, 43,527, 26.688,40.324 and7.676, respectively; P＜0.01). These parameters were higher in NHP group than in SNP, SHP and NNP groups (P＜0.05). HE and von kossa staining showed more evident vascular calcification in NHP group than in SNP, SHP and NNP groups. The expressions of Pit-1 and Cbfα1 were significantly different among the 5 groups (F=8.259 and 5.91, respectively; P＜0.01). Pit-1 and Cbfα1 expressions were significantly higher in NHP group than in SNP group (P＜0.01). The positive area ratios of Pit-1 and Cbfα1 were correlated with serum phosphorus level (r=0.344 and 0.376, respectively; P＜0.05). Serum creatinine, urea nitrogen, uric acid, phosphorus and urine protein levels were significantly lower in THP (STS treatment) group than in NHP group (P＜0.05). Also, the expressions of Pit-1 and Cbfα1 on aorta were significantly lower in SHP group than in NHP group (P＜0.01), while aorta calcification was alleviated partly in SHP group.  Conclusion  We successfully established a vascular calcification model in remnant kidney rats. STS treatment decreased serum phosphate, improved renal function, and delayed the progression of vascular calcification. Its effect is encouraging, but the underlying mechanisms require to be further studied.

Key words: Vascular calcification, Phosphorous, Remnant kidney rats, Sodium thiosulfate