【原】CCBPC2025熱點討論-iPTH與血管鈣化的關聯(lián)

2025年7月2日-7月5日，中華醫(yī)學會腎臟病分會重癥與血液凈化分會年會于天津召開，大會圍繞急慢性重癥腎臟病，以及血液透析、腹膜透析與連續(xù)性腎臟替代治療等新技術和新理論、并發(fā)癥防治以及臨床實踐中的常見問題，以大會報告、專題講座等形式展開深入的學術交流。其中，iPTH與血管鈣化的關聯(lián)成為大會的熱點話題，為此，協(xié)和麒麟醫(yī)學整理相關內容進行分享。

慢性腎臟病(Chronic kidney disease, CKD)患者由于長期的血鈣磷代謝失調，血管壁易出現(xiàn)礦物質沉積，即血管鈣化(Vascular calcification)。在 CKD 患者中，可以觀察到不同于普通基礎疾病的一些鈣化危險因素，隨著血管鈣化風險增加，心血管事件發(fā)生的概率也在上升，從而導致慢性腎臟病患者預后不佳。一系列證據(jù)表明，完整的甲狀旁腺激素（iPTH）水平與血管鈣化（VC）之間存在密切關聯(lián)。以下從多個角度分析iPTH在血管鈣化中的作用及其機制。

1. iPTH與血管鈣化的直接關系

研究表明，iPTH水平的升高與血管鈣化的進展顯著相關。在CKD患者中，iPTH水平過高會直接促進血管平滑肌細胞（VSMCs）向成骨樣細胞轉化，從而導致血管鈣化^3,6。此外，iPTH通過激活甲狀旁腺激素1受體（PTH1R）和蛋白激酶A（PKA）信號通路，增加鈣沉積，進一步加劇血管鈣化^6,18（圖1）。

圖1 動物試驗發(fā)現(xiàn)iPTH通過激活PTH1R、PKA等通路導致血管鈣化加重

2. iPTH與骨-血管軸的相互作用

iPTH在骨-血管軸中扮演重要角色。它通過調節(jié)RANK/RANKL/骨保護素（OPG）系統(tǒng)，不僅影響骨代謝，還促進血管鈣化^6,11（圖2）。在CKD患者中，iPTH水平升高會導致骨吸收增加和骨密度降低，同時加速血管鈣化的進程^3,14。

圖2: 骨代謝主要通路（RANK-RANKL-OPG-LGR4系統(tǒng)與Wnt/β-連環(huán)蛋白通路）及其在血管鈣化中的作用，以及甲狀旁腺激素（PTH）和磷（P）對這兩條通路的主要調控效應

3. iPTH與礦物質代謝紊亂

iPTH水平的升高通常伴隨高磷血癥和低鈣血癥，這些礦物質代謝紊亂進一步加劇血管鈣化^3,16。高磷環(huán)境會促進VSMCs的鈣化，而iPTH通過增強磷的吸收和減少鈣的排泄，進一步加速這一過程^3,9。

4. iPTH與炎癥和氧化應激

iPTH還與炎癥和氧化應激相關，這些因素在血管鈣化中起重要作用。研究表明，iPTH水平升高會誘導內質網(wǎng)應激，導致VSMCs凋亡和鈣化¹⁸。此外，iPTH通過激活炎癥通路，如BMP-2/Runx2信號通路，進一步促進血管鈣化¹⁹（圖3）。

圖3: 實時熒光定量PCR檢測顯示，慢性血液透析組PTHrP、Cbfa1及BMP-2的mRNA表達水平（D）較對照組明顯升高。*與對照組相比P < 0.05。放大倍數(shù)：×40。

5. 臨床意義與治療策略

在CKD患者中，控制iPTH水平是預防和治療血管鈣化的重要策略。研究表明，通過使用鈣敏感受體激動劑（如依伏卡塞、西那卡塞）或調整飲食中的鎂攝入量，可以有效降低iPTH水平，從而減緩血管鈣化的進展^1,2。其中新型口服擬鈣劑依伏卡塞已證實在中國人群中具有更好的降低iPTH的療效，并且降低了胃腸道的不良反應²⁰。此外，早期干預和長期隨訪對于改善患者預后至關重要^5,15，對CKD 3-5期患者定期監(jiān)測iPTH、鈣磷水平及血管鈣化標志物（如BMP-2、Runx2），以便及時調整治療方案，同時根據(jù)患者iPTH水平、鈣磷代謝狀態(tài)及并發(fā)癥風險，制定個性化用藥方案，避免過度抑制PTH導致低轉運骨病。

結論

iPTH與血管鈣化之間存在復雜的相互作用，涉及礦物質代謝紊亂、骨-血管軸失調、炎癥和氧化應激等多種機制。在CKD患者中，控制iPTH水平是預防和治療血管鈣化的關鍵。未來的研究應進一步探索iPTH在血管鈣化中的具體分子機制，以開發(fā)更有效的治療策略。

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