硫代硫酸钠早期干预对高磷诱导的残肾大鼠血管钙化的影响  

Early intervention of sodium thiosulfate attenuates high phosphorous induced vascular calcification in rats with remnant kidney

作　　者：余毅[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,福建福州350025

出　　处：《中华高血压杂志》2016年第4期348-353,共6页Chinese Journal of Hypertension

基　　金：福建省科技计划重点项目(2013Y0069)

摘　　要：目的探讨硫代硫酸钠(STS)早期干预对高磷诱导的残肾大鼠血管钙化的影响。方法 SD雄性大鼠35只随机分为5组:假手术+正常磷喂食(SNP组);假手术+高磷喂食(SHP组);残肾+正常磷喂食(NNP组);残肾+高磷喂食(NHP组);残肾+高磷喂食+STS治疗组(THP组),每组7只。分别行5/6肾切除或假手术,术后开始给予高磷或正常磷喂食16周(THP组给予STS 0.4g/kg腹腔注射)。16周后,大鼠处死前测量尾动脉血压,检测24h尿蛋白、血肌酐、钙、磷和全段甲状旁腺激素(iPTH)。取胸主动脉,采用Von Kossa和茜素红染色检测血管钙化,逆转录聚合酶链反应检测血管E11 mRNA表达,免疫组织化学和Western blot检测E11蛋白表达。结果与SNP组大鼠比较,NHP组大鼠血压[收缩压(156.6±10.2)比(105.4±3.4),舒张压(102.4±6.3)比(72.8±1.8)mm Hg]、血肌酐[(144.8±18.7)比(39.2±5.9)μmol/L]、磷[(2.63±0.22)比(1.92±0.10)mmol/L]、iPTH[(374.2±23.6)比(97.0±9.0)ng/L]和尿蛋白[(172.8±38.2)比(56.8±15.6)mg/24h]明显升高(均P<0.05);与NHP组比较,THP组血压[收缩压(129.1±11.5)比(156.6±10.2),舒张压(91.0±6.4)比(102.4±6.3)mm Hg]、血肌酐[(96.5±16.3)比(144.8±18.7)μmol/L]、磷[(2.30±0.27)比(2.63±0.22)mmol/L]、iPTH[(260.6±46.0)比(374.2±23.6)ng/L]和尿蛋白[(92.5±36.6)比(172.8±38.2)mg/24h]下降(均P<0.05)。NNP组主动脉仅散在点状钙盐沉积,而NHP组主动脉出现明显的线状钙盐沉积;STS治疗后血管钙盐沉积减少。与SNP组相比,NHP组血管E11mRNA和蛋白表达明显增加(均P<0.05);STS治疗后血管E11mRNA和蛋白表达较NHP组明显减少(均P<0.05)。结论 STS早期干预可下调E11的表达,减轻高磷诱导的残肾大鼠的血管钙化。Objective To observe the effects of early intervention by sodium thiosulfate（STS）on high phosphorus induced vascular calcification in rats with remnant kidney. Methods A total of 35 male Sprague Dawley rats were randomly divided into 5groups as follows：sham operation rats receiving normal phosphorus diet（SNP group,n=7）,sham operation rats receiving high phosphorus diet（SHP group,n=7）,remnant kidney rats receiving normal phosphorus diet（NNP group,n=7）,remnant kidney rats receiving high phosphorus diet（NHP group,n=7）,remnant kidney rats receiving high phosphorus diet and treatment with STS（THP group,n=7）. After the operation of 5/6nephrectomy or sham operation,they were fed with normal or high phosphorus diet for 16weeks（THP group was treated with 0.4g/kg STS,intraperitoneal injection）. After 16 weeks,The blood pressure of caudal artery was measured,24-hour urine protein,the levels of serum creatinine,calcium,phosphorus and intact parathyroid hormone（iPTH）were detected. Both Von Kossa staining and Alizarin red staining were used to detect vascular calcification in thoracic aorta. The protein expression of E11 in the aorta was detected by immunohistochemical methods and Western blot,and mRNA expression of E11 was detected by reverse transcription-polymerase chain reaction. Results The blood pressure [systolic blood pressure（156.6±10.2）vs（105.4±3.4）,diastolic blood pressure（102.4±6.3）vs（72.8±1.8）mm Hg],serum creatinine[（144.8±18.7）vs（39.2±5.9）μmol/L],phosphorus[（2.63±0.22）vs（1.92±0.10）mmol/L],iPTH [（374.2±23.6）vs（97.0±9.0）ng/L]and uric protein[（172.8±38.2）vs（56.8±15.6）mg/24h]in the NHP group were significantly higher than those in the SNP group（all P0.05）. After the treatment with STS,the blood pressure [systolic blood pressure（129.1±11.5）vs（156.6±10.2）,diastolic blood pressure（91.0±6.4）vs（102.4±6.3）mm Hg],serum creatinine[（96.5±16.3）vs（144.8±18.7）μmol/L],phosphorus [（2.30±0.27）vs（2

关 键 词：血管钙化 E11 残肾大鼠 硫代硫酸钠 

分 类 号：R692.5[医药卫生—泌尿科学]