氢氧化镧通过阻断HIF-1α信号通路抑制慢性肾病所致的血管钙化  

Lanthanum hydroxide inhibits CKD-induced vascular calcification by blocking HIF-1αsignaling pathway

作　　者：崔雅婷 王琪雯 王胜男 李刚 CUI Ya-ting;WANG Qi-wen;WANG Sheng-nan;LI Gang(Dept of Pharmacy,the First Hospital of Hohhot,Inner Mongolia Medical University,Hohhot 010110,China;Dept of Pharmacology,School of Pharmacy,Inner Mongolia Medical University,Hohhot 010110,China)

机构地区：[1]内蒙古自治区呼和浩特市第一医院药剂科,内蒙古呼和浩特010110 [2]内蒙古医科大学药学院药理学教研室,内蒙古呼和浩特010110

出　　处：《中国药理学通报》2023年第12期2354-2360,共7页Chinese Pharmacological Bulletin

基　　金：内蒙古自治区科技重大专项资助项目(No zdzx201805);内蒙古自治区自然科学基金资助项目(No 2022JQ01)。

摘　　要：目的研究氢氧化镧对慢性肾病(chronic kidney disease,CKD)所致大鼠肾损伤及血管钙化的治疗作用及其机制。方法通过给予腺嘌呤构建CKD模型,造模后随机分为模型组、氢氧化镧低、中、高剂量组、碳酸镧组、碳酸钙组。8周后,检测血清磷(Pi)、钙(Ca)、血肌酐(serum creatinine,Scr)、血尿素氮(blood urea nitrogen,BUN)、甲状旁腺激素(parathyroid hormone,PTH)、成纤维细胞生长因子23(fibroblast growth factor 23,FGF23)、抗酒石酸酸性磷酸酶5b(tartrate-resistant acid phosphatase 5b,TRAP-5b)水平;组织病理学染色评估血管钙化程度;对血管中平滑肌蛋白22α(smooth muscle protein 22α,SM22α)、Runt相关转录因子2(Runt-related transcription factor 2,RUNX2)、低氧诱导因子1(hypoxia inducible factor 1,HIF-1)通路mRNA及其蛋白表达水平进行检测。结果氢氧化镧可明显降低CKD大鼠血清Pi、Scr、BUN、PTH、FGF23及TRAP-5b水平,明显减少CKD大鼠胸主动脉的钙沉积、胞质中BMP-2、VEGF及胞核内RUNX2、HIF-1α的表达,增加SM22αmRNA及蛋白的表达。结论氢氧化镧可明显改善CKD大鼠高磷血症,其可能通过阻断HIF-1α信号通路发挥改善CKD大鼠血管钙化的作用。Aim To investigate the therapeutic effect of lanthanum hydroxide on renal injury and vascular calcification in rats caused by chronic kidney disease(CKD)and the underlying mechanism.Methods A CKD model was constructed by adenine,and the rats were randomly divided into model group,lanthanum hydroxide low,medium and high dose groups,lanthanum carbonate group and calcium carbonate group.After eight weeks,serum phosphorus(Pi),calcium(Ca),serum creatinine(Scr),blood urea nitrogen(BUN),parathyroid hormone(PTH),fibroblast growth factor 23(FGF23)and tartrate-resistant acid phosphatase 5b(TARP-5b)levels were measured.Histopathological staining was used to assess the degree of calcification of blood vessels,and the expressions of smooth muscle protein 22α(SM22α),Runt-related transcription factor 2(RUNX2),hypoxia inducible factor 1(HIF-1)pathway mRNA and protein expression in blood vessels were detected.Results Lanthanum hydroxide can significantly reduce the levels of Pi,Scr,BUN,PTH,FGF23 and TARP-5b in the serum of CKD rats,significantly reduce the calcium deposition of the thoracic aorta of CKD rats,the expression of BMP-2,VEGF in the cytoplasm,the expression of RUNX2,HIF-1αin the nucleus,and increase the mRNA and protein expression of SM22.Conclusion Lanthanum hydroxide can markedly improve hyperphosphatemia in CKD rats,and can improve vascular calcification in CKD rats by blocking HIF-1αsignaling pathway.

关 键 词：氢氧化镧 慢性肾病 腺嘌呤 高磷血症 血管钙化 低氧诱导因子1Α 

分 类 号：R-332[医药卫生] R589.5R692.5R845.22R916.3