氢氧化镧抑制慢性肾衰高磷血症所致血管钙化的作用机制

THE MECHANISM OF LANTHANUM HYDROXIDE IN INHIBITING VASCULAR CALCIFICATION CAUSED BY CHRONIC RENAL FAILURE AND HYPERPHOSPHATEMIA

目的:研究氢氧化镧对慢性肾衰竭血管钙化的药理学作用,探究NF-κB通路对慢性肾衰血管钙化的影响。方法:使用腺嘌呤建立Wistar大鼠慢性肾衰模型,造模成功后,将模型鼠随机分为氢氧化镧低、中、高剂量组(LH 0.1,0.2,0.4 g/kg)、碳酸镧组(LC 0.3 g/kg)、碳酸钙组(CC 0.42 g/kg)和Model组,另选15只Wistar大鼠作为Control组。给药8周后进行血清中的磷,钙,肌酐,尿素氮,甲状旁腺素(PTH)和成纤维细胞生长因子23(FGF23)的检测,胸主动脉的Von-kossa、EVG染色进行组织病理学观察,qRT-PCR和Western Blot检测SM22α、Runx2以及NF-κB通路TRAF6和NF-κB的基因及蛋白的表达情况。结果:(1)氢氧化镧可显著降低CKD大鼠血清磷、肌酐、尿素氮、PTH、FGF23血清水平。(2)氢氧化镧各剂量组均可减少胸主动脉钙化沉积,改善弹性纤维的断裂。(3)氢氧化镧可剂量依赖性升高SM22α的蛋白表达,降低Runx2、TRAF6和细胞核内NF-κB的蛋白表达。结论:(1)氢氧化镧可通过调节钙磷代谢,抑制血管钙化的发生及发展。(2)氢氧化镧抑制血管钙化的作用机制可能是通过抑制NF-κB通路的激活实现的。

Objective:To study the pharmacological effects of lanthanum hydroxide on vascular calcification in chronic renal failure,and to explore the effect of NF-κB pathway on vascular calcification in chronic renal failure.Methods:The Wistar rat chronic renal failure model was established using adenine.After the model was successful,the model rats were divided into lanthanum hydroxide low,medium,and high dose groups(LH 0.1,0.2,0.4 g/kg),and lanthanum carbonate group(LC 0.3 g/kg),calcium carbonate group(CC 0.42 g/kg)and Model group,15 Wistar rats were selected as the Control group.After 8 weeks of administration,the serum levels of phosphorus,calcium,creatinine,urea nitrogen,parathyroid hormone(PTH)and fibroblast growth factor 23(FGF23)were detected,and the thoracic aorta was stained with Von-kossa and EVG.Pathological observation,qRT-PCR and Western Blot to detect SM22α,Runx2,and NF-κB pathway TRAF6 and NF-κB gene and protein expression.Results:(1)Lanthanum hydroxide can significantly reduce the serum levels of phosphorus,creatinine,urea nitrogen,PTH,and FGF23 in CKD rats.(2)Each dose group of lanthanum hydroxide can reduce thoracic aortic calcification and improve the breakage of elastic fibers.(3)Lanthanum hydroxide can increase the protein expression of SM22αin a dose-dependent manner,and decrease the protein expression of Runx2,TRAF6 and NF-κB in the nucleus.Conclusion:(1)Lanthanum hydroxide can inhibit the occurrence and development of vascular calcification by regulating calcium and phosphorus metabolism.(2)The mechanism of lanthanum hydroxide inhibiting vascular calcification may be achieved by inhibiting the activation of the NF-κB pathway.