慢性肾脏病血管钙化大鼠模型血清中HIF⁃1α、β⁃catenin的表达及意义

Significance of detection of serum HIF-1αandβ-catenin in rat model of vascular calcification in chronic kidney disease

目的:建立慢性肾脏病(chronic kidney disease,CKD)血管钙化大鼠模型,探讨血清低氧诱导因子-1α(HIF-1α)、β-连环蛋白(β-catenin)水平与血管钙化的相关性。方法:将30只雄性SD大鼠随机分为正常对照组(CON组,10只)和CKD血管钙化组(CKD组,20只),血管钙化组大鼠给予腺嘌呤灌胃及高磷饲料喂养。第6周末收集两组大鼠血、尿液分别检测肾功、钙、磷及24 h尿蛋白定量等;留取肾组织行HE染色;大鼠主动脉行Von Kossa染色及钙含量测定;ELISA法检测血清中HIF-1α、β-catenin水平。结果:与CON组相比,CKD组大鼠24 h尿蛋白定量、血BUN、Scr、P、Ca×P、主动脉钙含量、血清HIF-1α、β-catenin水平均明显增加,血钙降低(P均<0.05);CKD组大鼠见肾小球萎缩、肾小管扩张及肾间质纤维化;主动脉可见明显的钙化结节,Von Kossa染色可见较多黑色物质沉积;血清HIF-1α、β-catenin水平与血P、Ca×P与大鼠主动脉钙含量呈正相关(P均<0.05)。结论:CKD血管钙化时血清HIF-1α、β-catenin水平明显增高,且与主动脉钙化程度明显相关。

Objective:To investigate the association between serum HIF-1α,β-catenin levels and the vascular calcification in the rat model of chronic kidney disease(CKD)vascular calcification.Methods:A total of 30 SD male rats were randomly divid-ed into the normal control group(CON group,n=10)and the CKD vascular calcification group(CKD group,n=20).Rats in the calcification group were fed with adenine combined with high phosphorus diet.At the end of the 6th week,the blood and urine of the two groups were collected to detect renal function,calcium,phosphorus and 24 h urinary protein.The renal tissue was stained with H&E,the aorta of rats was stained with Von Kossa and calcium content was determined,and the levels of HIF-1αandβ-catenin in serum were detected by ELISA method.Results:Compared with the CON group,24 h urinary protein,blood BUN,Scr,P,Ca×P,aortic calcium content,serum HIF-1αandβ-catenin levels were significantly increased and serum calcium decreased in the CKD group(P<0.05).Glomerular atrophy,renal tubule dilatation and interstitial fibrosis were seen in the CKD group,and Von Kossa staining of calcified nodules in aorta showed more black substance deposition.The levels of serum HIF-1α,β-catenin and serum P,Ca×P were positively correlated with the content of calcium in rat aorta.Conclusion:The levels of serum HIF-1αandβ-catenin are significantly increased in patients with vascular calcification in CKD,and they are significantly related to the degree of aortic calcification.