Zhao Lulu, Wang Shengnan, Liu Hong, Du Xiaoli, Bu Ren, Li Bing, Han Ruilan, Gao Jie, Liu Yang, Hao Jian, Zhao Jianrong, Meng Yan, Li Gang
Department of Pharmacology, College of Pharmacy, Inner Mongolia Medical University, Jinshan Development, Hohhot, China.
Department of Nephrology, The Affiliated Hospital of Inner Mongolia Medical University, Hohhot, China.
Front Cell Dev Biol. 2021 Apr 13;9:639127. doi: 10.3389/fcell.2021.639127. eCollection 2021.
The present work aimed to explore the efficacy of lanthanum hydroxide in managing the vascular calcification induced by hyperphosphate in chronic renal failure (CRF) as well as the underlying mechanism.
Rats were randomly allocated to five groups: normal diet control, CKD hyperphosphatemia model, CKD model treated with lanthanum hydroxide, CKD model receiving lanthanum carbonate treatment, together with CKD model receiving calcium carbonate treatment. The serum biochemical and kidney histopathological parameters were analyzed. The aortic vessels were subjected to Von Kossa staining, CT scan and proteomic analysis. , the calcium content and ALP activity were measured, and RT-PCR (SM22α, Runx2, BMP-2, and TRAF6) and Western blot (SM22α, Runx2, BMP-2, TRAF6, and NF-κB) were performed.
In the lanthanum hydroxide group, serum biochemical and kidney histopathological parameters were significantly improved compared with the model group, indicating the efficacy of lanthanum hydroxide in postponing CRF progression and in protecting renal function. In addition, applying lanthanum hydroxide postponed hyperphosphatemia-mediated vascular calcification in CKD. Furthermore, lanthanum hydroxide was found to mitigate vascular calcification via the NF-κB signal transduction pathway. For the cultured VSMCs, lanthanum chloride (LaCl) alleviated phosphate-mediated calcification and suppressed the activation of NF-κB as well as osteo-/chondrogenic signal transduction. Lanthanum hydroxide evidently downregulated NF-κB, BMP-2, Runx2, and TRAF6 expression.
Lanthanum hydroxide protects against renal failure and reduces the phosphorus level in serum to postpone vascular calcification progression.
本研究旨在探讨氢氧化镧对慢性肾衰竭（CRF）高磷血症诱导的血管钙化的治疗效果及其潜在机制。
将大鼠随机分为五组：正常饮食对照组、CKD高磷血症模型组、氢氧化镧治疗的CKD模型组、碳酸镧治疗的CKD模型组以及碳酸钙治疗的CKD模型组。分析血清生化和肾脏组织病理学参数。对主动脉血管进行冯科萨染色、CT扫描和蛋白质组学分析。测量钙含量和碱性磷酸酶（ALP）活性，并进行逆转录聚合酶链反应（RT-PCR，检测SM22α、Runx2、骨形态发生蛋白-2（BMP-2）和肿瘤坏死因子受体相关因子6（TRAF6））及蛋白质免疫印迹法（Western blot，检测SM22α、Runx2、BMP-2、TRAF6和核因子κB（NF-κB））。
与模型组相比，氢氧化镧组的血清生化和肾脏组织病理学参数显著改善，表明氢氧化镧在延缓CRF进展和保护肾功能方面具有疗效。此外，应用氢氧化镧可延缓CKD中高磷血症介导的血管钙化。此外，发现氢氧化镧可通过NF-κB信号转导通路减轻血管钙化。对于培养的血管平滑肌细胞（VSMCs），氯化镧（LaCl）可减轻磷酸盐介导的钙化，并抑制NF-κB的激活以及骨/软骨生成信号转导。氢氧化镧明显下调NF-κB、BMP-2、Runx2和TRAF6的表达。
氢氧化镧可预防肾衰竭并降低血清磷水平，从而延缓血管钙化进展。
