HIF-1α和HIF-PHI在慢性肾脏病血管钙化中的研究进展  

Progress of HIF-1αand HIF-PHI in vascular calcification of chronic kidney disease

作　　者：王澳 李相友 熊瑛[1] 唐春莲 谢亚平 WANG Ao;LI Xiangyou;XIONG Ying;TANG Chunlian;XIE Yaping(Department of Nephrology,Wuchang Hospital Affiliated to Wuhan University of Science and Technology,Wuhan 430063,China;School of Medicine,Wuhan University of Science and Technology,Wuhan 430065,China;Department of Pathology,Wuchang Hospital Affiliated toWuhan University of Science and Technology,Wuhan 430063,China)

机构地区：[1]武汉科技大学附属武昌医院肾病内科,武汉430063 [2]武汉科技大学医学部医学院,武汉430065 [3]武汉科技大学附属医院武昌医院病理科,武汉430063

出　　处：《广西医科大学学报》2024年第8期1200-1205,共6页Journal of Guangxi Medical University

基　　金：国家自然科学基金资助项目(No.82070810);湖北省重点实验室联合基金资助项目(No.JF2023-G14)。

摘　　要：慢性肾脏病已成为全球公共卫生的重大挑战,心血管疾病是其首要致死原因。血管钙化表现为钙和磷酸盐矿物质在动脉壁的病理性沉积,可导致血管硬化、管腔狭窄,不仅影响肾脏的血流供应,还增加心血管疾病的风险。在慢性肾脏病的病理环境下,肾脏持续处于低氧状态,低氧诱导因子-1α(HIF-1α)作为关键的转录因子,对细胞适应低氧环境至关重要。HIF-1α通过促进血管平滑肌细胞成骨样分化等多条途径,影响慢性肾脏病血管钙化的进展。低氧诱导因子脯氨酸羟化酶抑制剂(HIFPHI)是肾性贫血的新型口服治疗药物,可以通过激活人体对缺氧的自然生理反应,抑制HIF的降解以促进红细胞生成,增加内源性促红细胞生成素的产生。HIF-PHI有促进血管钙化的可能,其促钙化作用与HIF-1α的稳定性密切相关。因此,充分了解HIF-PHI在血管钙化中潜在的危害性并加以重视意义重大。Chronic kidney disease has become a major global public health challenge,and cardiovascular dis-ease is the leading cause of death.Vascular calcification is characterized by pathological deposition of calcium and phosphate minerals in the arterial wall,which can lead to vascular sclerosis and lumen narrowing.This not only affects the blood supply to the kidneys,but also increases the risk of cardiovascular disease.In the pathologi-cal setting of chronic kidney disease,the kidneys are in a constant state of hypoxia.Hypoxia inducible factors 1 alpha(HIF-1α),as a key transcription factor,is essential for cellular adaptation to the hypoxic environment.HIF-1αaffects the progression of vascular calcification in chronic kidney disease through multiple pathways,notably by encouraging osteoblast-like differentiation in vascular smooth muscle cells.Hypoxia-inducible factor-prolyl hydroxylase inhibitor(HIF-PHI)is a novel oral treatment for renal anemia that can inhibit the degradation of HIF to promote erythropoiesis and increase endogenous erythropoietin production by activating the body’s natural physiological response to hypoxia.Studies have shown that HIF-PHI has the potential to promote vascular calcifi-cation,and its pro-calcification effects are closely related to the stability of HIF-1α.Therefore,it is important to fully understand the potential harmful effects of HIF-PHI in vascular calcification and pay attention to it.

关 键 词：慢性肾脏病 血管钙化 低氧诱导因子-1Α 低氧诱导因子脯氨酸羟化酶抑制剂 

分 类 号：R692.5[医药卫生—泌尿科学] R543.1[医药卫生—外科学]