细胞核因子κB配体活化因子在肺高压中的作用

Role of RANKL in pulmonary hypertension

目的 :评估细胞核因子κB配体活化因子(receptor activator of nuclear facto-κB ligand,RANKL)在肺高压(pulmonary hypertension,PH)中的表达水平及其作用。方法:本研究涉及临床和动物实验两部分。临床实验以48例PH患者和50例无肺高压(non-PH)对照者作为研究对象,采用酶联免疫吸附试验检测其血清RANKL水平,并用超声心动图评估其心功能。对于PH组中8例接受靶向治疗的患者,观察2年随访期内其RANKL的变化。动物实验采用低氧(10%O2)诱导的PH小鼠模型,检测其右心室收缩压、右心室肥大情况,以评估其疾病严重程度,并用反转录聚合酶链反应(reverse transcription-polymerase chain reaction,RT-PCR)等方法检测小鼠血清、肺组织中RANKL水平。结果:临床研究结果示,PH患者的血清RANKL水平显著高于对照者[(4.00±0.30)pmol/L比(2.23±0.14)pmol/L],且RANKL水平与其疾病严重程度呈正相关;PH患者治疗后测得的血清RANKL水平较治疗前降低。动物实验中,低氧诱导的PH模型小鼠的血清、肺组织及肺动脉中的RANKL水平均显著高于对照组小鼠。结论:RANKL在PH中升高,不仅可作为提示PH诊断的指标,且在随访及疗效评估中也有着重要意义。

Objective： To investigate the expression and role of receptor activator of nuclear factor KB ligand（RAN- KL） in pulmonary hypertension （PH）. Methods： In clinical studies, serum RANKL （sRANKL） levels in 48 PH patients and 50 controls were assayed by ELISA. Echocardiography was performed to assess their heart function. In laboratory studies, chronic hypoxia （10% 02） induced mouse PH model were established in WT mice and RT-PCR was used to de- tect expression of RANKL both in serum and lung tissue. Results： sRANKL concentration was elevated in PH patients when compared with controls, and sRANKL level was positively correlated with the severity of PH disease represented by 6-rain walking distance （6MWD） and WHO classification, sRANKL level decreased in patients who responded to targeted treatment. In hypoxia-induced PH mouse model, expression of RANKL was increased both in serum and lung tissue. Conclusions： sRANKL could be an indicator not only for the occurrence of PH, but also for the follow-up and therapy evaluation in PH patients. It is expected to be a new biomarker for PH.