核因子-κB受体的配体在动脉钙化中的作用及其意义  

The role and its significance of the receptor activator of nuclear factor-κB ligand in arterial calcification

作　　者：聂斌[1] 管思明[2] 张韶英[1] 周韶琼 方欣 

机构地区：[1]华中科技大学同济医学院附属武汉市中心医院老年病科,430014 [2]华中科技大学同济医学院附属武汉协和医院老年病科,430012

出　　处：《中华老年医学杂志》2018年第2期206-210,共5页Chinese Journal of Geriatrics

基　　金：武汉市卫生计生委科研基金资助（WX15C42）

摘　　要：目的探讨核因子（NF-κB）受体的配体（RANKL）很可能具有促破骨样细胞分化的功能，却在很多研究中显示出促钙化作用的原因。方法在破骨样细胞前体的培养液中加入RANKL，用光镜观察和抗酒石酸染色（TRAP染色）检测其是否能促进破骨样细胞的分化；在体内和体外两方面，用同样方法观察在钙化过程中破骨样细胞的表达情况，同时用实时定量PCR（RT—PCR）法检测此过程中伴随的RANKL及其拮抗物骨保护素（OPG）的表达情况。结果单独培养时RANKL对破骨样细胞分化确实有明显的促进作用，然而无论在体内或体外，正常组和钙化早期组中都没有破骨样细胞的表达，此时检测的RANKL／OPG的比值均很低。只有在钙化晚期组中发现有少量的破骨样细胞表达，此时RANKL／0PG的比值较早期明显升高，动物模型中钙化组早晚期RANKL/OPG比值分别为0．36±0．08（F=363，1．68±0．08（F=36），对照组早晚期RANKL／OPG比值均为0（均P〈0．05）；细胞模型中钙化组早晚期RANKL／0PG比值分别为0．42±0．09（F=16），1．50±0．10（F=16），对照组中早晚期RANKL／OPG比值均为0（均P％0．05）。结论钙化过程的大部分阶段，动脉中RANKL／OPG的比值较低，致使RANKL促破骨样细胞分化的功能完全被OPG所抑制，很可能就是造成RANKL具有促破骨样细胞分化的功能却不能表现出抑钙化作用的主要原因。Objective To investigate the mechanism that receptor activator of NF-κB ligand （RANKL） promotes arterial calcification. Methods Firstly, RANKL was added into the culture media, in which the monocyte precursor cells alone were cultured. Morphological observation and tartrate resistant acid phosphatase（TRAP）stain were used to assess whether RANKL could induce the monocyte precursor cells to differentiate into osteoclast-like cells. During arterial calcification, both in vivo and in vitro expressions of RANKL and osteoprotegerin （OPG, as RANKL inhibitor）were measured via real-time PCR. The extent of osteoclast-like cell differentiation was also assessed. Results It was found that RANKL could induce osteoclast-like cell differentiation. There were no both in vivo and in vitro expressions of osteoclast-like cells in the early stage of calcification. At that time, the ratio of RANKL to OPG was very low. In the late stage of calcification, a small amount of osteoclast like cell expression coincided with a relatively high ratio of RANKL to OPG. According to the results, the ratio of RANKL to OPG was very low during most of the arterial calcification period. This made it possible for OPG to completely inhibit RANKL-induced osteoclast-like cell differentiation. The ratio of RANKL to OPG was（0.36± 0.08） （F= 36） and（1.68±0.08） （F=36） respectively in the early and late subgroup of calcification group in the animal model, but was zero in the control group（ both P〈0.05 ）. The ratio of RANKL to OPG was（0.42 ± 0.09 ） （F= 16 ） and（ 1.50 ± 0. 10）（F=16）respectively in the early and late subgroup of calcification group in the cell model, but was zero in the control group（both P〈0.05）. Conclusions Our result likely explains why RANKL has the ability to induce osteoclast-like cell differentiation,but acts as a promoter of calcification.

关 键 词：NF-ΚB 破骨细胞 动脉钙化 

分 类 号：R543.5[医药卫生—心血管疾病]