CD248蛋白在肺动脉高压中的表达及其临床意义

Expression of CD248 in pulmonary arterial hypertension and its clinical significance

目的 研究肺动脉高压(pulmonary arterial hypertension, PAH)患者的血浆CD248水平及其临床意义。方法 共纳入本科于2016年3月至2019年6月经右心导管检查明确诊断的PAH患者30例和健康对照者12例,其中PAH患者包括14例特发性肺动脉高压(idiopathic pulmonary arterial hypertension, IPAH)患者和16例慢性肺栓塞型肺动脉高压(chronic thromboembolic pulmonary hypertension, CTEPH)患者。使用ELISA检测健康对照者和PAH患者血浆中CD248蛋白水平。使用野百合碱(monocrotaline, MCT)诱导Sprague Dawley大鼠PAH,通过ELISA检测大鼠血浆中CD248蛋白表达。进一步通过体外实验予以肿瘤坏死因子α(tumor necrosis factor-α, TNF-α)或血小板源生长因子BB(platelet-derived growth factor-BB, PDGF-BB)干预大鼠肺动脉平滑肌细胞(pulmonary artery smooth muscle cells, PASMCs),检测CD248 mRNA的表达。结果 PAH患者血浆中的CD248水平明显低于健康对照者(P<0.01)。受试者工作特征曲线(receiver operating characteristic curve, ROC)下面积(area under the curve, AUC)为0.79(95%CI:0.64~0.94,P<0.01)。同样地,野百合碱处理组大鼠血浆中CD248蛋白水平均较对照组降低。血小板源生长因子BB干预后,PASMCs中CD248 mRNA的表达先上调后下调。结论 CD248在PAH患者血浆中表达降低,其具有作为生物标记物用于辅助诊断PAH的潜力。

Objective Too investigate the plasma level of CD248 in patients with pulmonary arterial hypertension(PAH) and its clinical significance. Methods A total of 30 PAH patients, including 14 with idiopathic pulmonary arterial hypertension(IPAH) and 16 with chronic thromboembolic pulmonary hypertension(CTEPH) who were diagnosed by right heart catheterization in the our department from March 2016 to June 2019 were recruited, and 12 healthy individuals who taking physical examination during same period served as control group in this study. Plasma levels of CD248 protein in healthy controls and PAH patients were detected using ELISA. After monocrotaline(MCT) was used to induce PAH in SD rats, and the level of CD248 in rat plasma was also detected by ELISA. Then in vitro, after rat pulmonary artery smooth muscle cells(PASMCs) were isolated and identified and then cultured to passages 5~7, they were treated with TNF-α or platelet-derived growth factor-BB(PDGF-BB), and the mRNA expression of CD248 in the cells was measured with qPCR. Results The plasma level of CD248 was significantly lower in the PAH patients than the healthy controls(P<0.01). Its area under the curve(AUC) of the receiver operating characteristic(ROC) curve for PAH was 0.79(95%CI: 0.64~0.94, P<0.01). Similarly, the level of CD248 in the plasma of rats was lower in the MCT treatment group than the control group. After the intervention of PDGF-BB, the mRNA level of CD248 in PASMCs was first up-regulated and then down-regulated. Conclusion CD248 is lowly expressed in the plasma of PAH patients, and it has the potential to be used as a biomarker to assist in the diagnosis of PAH.