硫代硫酸钠减轻高磷诱导5／6肾切除大鼠的血管钙化  

Sodium thiosulfate attenuates high phosphorous induced vascular calcification in rats with 5/6 nephrectomy

作　　者：余毅[1] 黄恬[1] 霍苗苗[1] 王琰[1] 

机构地区：[1]南京军区福州总医院血液净化科福建医科大学福州总医院临床医学院,福州350025

出　　处：《中华肾脏病杂志》2016年第3期212-218,共7页Chinese Journal of Nephrology

基　　金：福建省科技计划重点项目（2013Y0069）

摘　　要：目的观察Klotho基因和钠磷共转运体在5／6肾切除（残肾）加高磷诱导的慢性肾衰竭大鼠模型血管和肾脏中的表达及其与血管钙化的关系；探讨硫代硫酸钠（STS）早期干预减轻血管钙化的机制。方法35只SD雄性大鼠动物被分为5组：（I）假手术＋正常磷饮食（SNP）组；（2）假手术＋高磷饮食（SHP）组；（3）残肾＋正常磷饮食（NNP）组；（4）残肾＋高磷饮食（NHP）组；（5）残肾＋高磷饮食＋STS治疗（THP）组。各组大鼠分别接受5／6肾切除（n=21）或假手术（n=14），术后分别给予高磷或正常磷饮食16周；STS治疗组给予STS腹腔注射，每周3次。16周后，测量各组大鼠尾动脉血压，检测血肌酐、血钙、血磷、成纤维细胞生长因子23（FGF23）、全段甲状旁腺素（iPTH）和24h尿蛋白量。Vonkossa染色法检测胸主动脉钙化程度；免疫组织化学法检测血管Klotho和钠磷共转运体Pit-1表达；PASM．Masson染色观察肾组织病理改变；实时定量PCR法检测肾组织Klotho和NaPi-2amRNA表达。结果与SNP大鼠相比，NHP组大鼠动脉血压、血肌酐、血磷、FGF23、iPTH水平和24h尿蛋白量明显升高（均P〈0．05）。与NHP组相比，THP组大鼠血压、Scr、血磷、FGF23、iPTH水平和24h尿蛋白量明显下降（均P〈0．05）。16周后NHP组肾组织呈现慢性肾衰竭病理改变。SNP和SHP组大鼠主动脉未见明显钙化；NHP组大鼠主动脉呈现严重钙化；与THP组相比，NHP组大鼠血管钙化明显减轻（P〈0．05）。与SNP组相比，NHP组大鼠主动脉和肾脏Klotho表达明显减少，Pit-1和NaPi．2a表达明显增多（均P〈0．05）；与NHP组相比，THP组大鼠主动脉和肾组织的Klotho表达明显增加（均P〈0．05），Pit-1和NaPi-2a表达明显减少（均P〈0．05）。结论STS早期干预可调节5／6肾切除加高磷诱导的慢性肾衰竭大鼠血管和肾脏Klotho与钠磷共转运体的表达。STS有纠�Objective To observe the expression of Klotho and Na＊/Pi cotransporter in high phosphorous-induced rats with 5/6 nephrectomy and its relationship with vascular calcification, as well as to investigate the effect of early intervention by sodium thiosulfate （STS） on the progression of vascular calcification. Methods Either 5/6 nephreetomy （n=21） or sham operation （n=14） was conducted on 35 Sprague Dawley rats, who were then fed with high phosphorus （HP） diet or normal phosphorus （NP） diet for 16 weeks respectively. The rats were divided into 5 groups as follows： （1）remnant kidney rats receiving HP diet （NHP, n=7）, （2） remnant kidney rats receiving NP diet （NNP, n= 7）, （3） sham operation rats receiving NP diet （SNP, n=7）, （4） sham operation rats receiving HP diet （SHP, n=7）, （5） remnant kidney rats receiving HP diet with STS （THP, n=7）. The treatment group was given STS intraperitoneally three times a week for 16 weeks. At the end of the 16th week, rats tail artery blood pressures were tested, serum creatinine （Scr）, calcium （Ca2＋）, phosphorus （p3＋）, FGF23, iPTH and urine protein were examined. Throacie aorta and kidney were then removed. Vascular calcification was confirmed by Von kossa staining. Klotho and Pit- 1 expression in aortas were determined by immunohistochemistry. Renal lesion was determined by PASM- Masson staining. Renal Klotho and NaPi-2a mRNA were determined by real time RT-PCR. Results After 16 weeks, Scr, p3＋, FGF23, iPTH, uric protein and blood pressure were significantly higher in NHP than those in SNP rats （all P 〈 0.05）. PASM - Masson staining revealed typical renal pathology of chronic renal failure in NHP group. With the treatment of STS, THP rats showed significant decrease in Scr, p3＋, FGF23, iPTH, uric protein and blood pressure by comparison with NHP group （all P 〈 0.05）. Significant vascular calcification was found in NHP group while NNP and SHP group occasionally had vascular calcification; T

关 键 词：钙化 血管 肾功能衰竭 慢性 硫代硫酸盐类 KLOTHO 钠磷共转运体 

分 类 号：R692.5[医药卫生—泌尿科学]