慢阻肺并发肺动脉高压患者血清CRP、IL-6和TLR4的差异表达及相关性分析
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摘要
目的探究血清C反应蛋白(C-reaction protein, CRP)、白介素-6 (interleukin-6, IL-6)和Toll样受体4 (toll-like receptors 4, TLR4)对慢性阻塞性肺疾病(chronic obstructive pulmonary disease, COPD)合并肺动脉高压(pulmonary hypertension,PAH)的早期诊断与发病风险预测的价值。方法收取我院2016年1月至2016年12月期间收治的COPD患者共70例,依据患者是否合并PAH分为两组:COPD合并PAH组40例;单纯COPD组30例。采用免疫比浊法(PETIA)测定CRP,采用酶联免疫吸附法(ELISA)测定IL-6和TLR4。结果 COPD合并PAH患者血清CRP、IL-6和TLR4水平均显著高于单纯COPD(P <0. 05)。依据血清CRP、IL-6和TLR4水平中位数对COPD合并PAH患者进行分组,高水平与低水平CRP、IL-6和TLR4组患者在不同年龄、性别和FEV1/FVC的差异均无统计学意义(P>0.05),而高水平CRP、IL-6和TLR4组的COPD急性加重(AECOPD)发生率及AECOPD平均发生次数均增高,且差异具有统计学意义(P<0.05)。血清CRP、IL-6和TLR4区分COPD合并PAH与单纯COPD的曲线下面积(AUC)分别为:0.767(95%CI:0·692～0. 881,P<0. 001)、0. 841 (95%CI:0.803～0. 920,P <0.001)和0.902(95%CI:0.836～0.974,P <0. 001);灵敏度及特异性分别为:77.1%/78.4%、76.6%/92.9%和93.2%/64.7%。联合三个指标时区分COPD合并PAH与单纯COPD的AUC为0.973 (95%CI:0. 936～0. 998,P <0. 001),"并联"时,约登指数最大时的灵敏度和特异性分别为97. 7%和60.1%,对应CRP、IL-6和TLR4的临界值分别为42.3 mg/L、71.8 pg/mL和26.6 mIU/mL;在"串联"时,约登指数最大时的灵敏度为73.6%,特异性为98.3%,对应的CRP、IL-6和TLR4临界值分别为41.8 mg/L、71.2 pg/mL和25. 7 mIU/mL。结论血清CRP、IL-6和TLR4对COPD并发PAH具有早期诊断价值。
Objective To explore the clinical values of serum C-reaction protein(CRP),interleukin-6(IL-6)and toll-like receptors 4(TLR4)in the early diagnosis and risk prediction of patients with chronic obstructive pulmonary disease(COPD) complicated with pulmonary hypertension(PAH). Methods A total of 70 patients with COPD admitted to our hospital from January,2016 to December,2016 were included for the study. These patients were divided into two groups according to whether the patients combined with PAH or not, which providing 40 patients in the COPD combined with PAH group and 30 patients in the simple COPD group.CRP was determined by immunoturbidimetric assay(PETIA) and IL-6 and TLR4 were measured by enzymelinked immunosorbent assay(ELIS A). Results The levels of serum CRP,IL-6 and TLR4 in patients with COPD combined with PAH were significantly higher than those in the simple COPD group(P <0. 05).According to the median levels of serum CRP,IL-6 and TLR4,COPD patients with PAH were grouped. There were no significant differences in age,sex and FEV1/FVC between high-level and low-level CRP,IL-6 and TLR4 groups(P >0.05). However,the incidence of acute exacerbation of COPD(AECOPD)and the average number of AECOPD in high-level CRP,IL-6 and TLR4 groups were increased, and the difference was statistically significant( P < 0. 05). The under the curve area( AUC) of serum CRP, IL-6 and TLR4 in differentiating COPD with PAH and simple COPD were 0. 767(95% CI: 0.692-0. 881,P< 0.001),0. 841(95% CI:0.803-0. 920,P<0.001)and 0.902(95% CI: 0. 836-0. 974,P <0. 001), the sensitivity and specificity were 77.1%/78.4%,76.6%/92.9% and 93. 2%/64.7%, respectively. When combined with the three indicators, the AUC in differentiating COPD combined with PAH and simple COPD was 0. 973(95%CI:0. 936-0. 998, P < 0. 001). When in parallel model, the sensitivity and specificity were 97.7% and60.1%, the corresponding CRP, IL-6 and TLR4 were judged under 42.3 mg/L, 71.8 pg/mL and26.6 mIU/mL,respectively. When in series model,the sensitivity was 73.6% and the specificity was 98. 3%,and the corresponding CRP,IL-6 and TLR4 were 41.8 mg/L,71.2 pg/mL and 25.7 mIU/mL,respectively.Conclusion Serum CRP,IL-6 and TLR4 have early diagnostic value for COPD complicated with PAH.
Objective To explore the clinical values of serum C-reaction protein(CRP),interleukin-6(IL-6)and toll-like receptors 4(TLR4)in the early diagnosis and risk prediction of patients with chronic obstructive pulmonary disease(COPD) complicated with pulmonary hypertension(PAH). Methods A total of 70 patients with COPD admitted to our hospital from January,2016 to December,2016 were included for the study. These patients were divided into two groups according to whether the patients combined with PAH or not, which providing 40 patients in the COPD combined with PAH group and 30 patients in the simple COPD group.CRP was determined by immunoturbidimetric assay(PETIA) and IL-6 and TLR4 were measured by enzymelinked immunosorbent assay(ELIS A). Results The levels of serum CRP,IL-6 and TLR4 in patients with COPD combined with PAH were significantly higher than those in the simple COPD group(P <0. 05).According to the median levels of serum CRP,IL-6 and TLR4,COPD patients with PAH were grouped. There were no significant differences in age,sex and FEV1/FVC between high-level and low-level CRP,IL-6 and TLR4 groups(P >0.05). However,the incidence of acute exacerbation of COPD(AECOPD)and the average number of AECOPD in high-level CRP,IL-6 and TLR4 groups were increased, and the difference was statistically significant( P < 0. 05). The under the curve area( AUC) of serum CRP, IL-6 and TLR4 in differentiating COPD with PAH and simple COPD were 0. 767(95% CI: 0.692-0. 881,P< 0.001),0. 841(95% CI:0.803-0. 920,P<0.001)and 0.902(95% CI: 0. 836-0. 974,P <0. 001), the sensitivity and specificity were 77.1%/78.4%,76.6%/92.9% and 93. 2%/64.7%, respectively. When combined with the three indicators, the AUC in differentiating COPD combined with PAH and simple COPD was 0. 973(95%CI:0. 936-0. 998, P < 0. 001). When in parallel model, the sensitivity and specificity were 97.7% and60.1%, the corresponding CRP, IL-6 and TLR4 were judged under 42.3 mg/L, 71.8 pg/mL and26.6 mIU/mL,respectively. When in series model,the sensitivity was 73.6% and the specificity was 98. 3%,and the corresponding CRP,IL-6 and TLR4 were 41.8 mg/L,71.2 pg/mL and 25.7 mIU/mL,respectively.Conclusion Serum CRP,IL-6 and TLR4 have early diagnostic value for COPD complicated with PAH.
引文
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[9] ARIAN A,MORTAZAVI MOGHADAM S G,KAZEMI T,et al. Trial of Atorvastatin on Serum Interleukin-6,Total Antioxidant Capacity,C-Reactive Protein, and Alpha-1 Antitrypsin in Patients with Chronic Obstructive Pulmonary Disease[J]. J Res Pharm Pract,2018,7(3):141-146.
[10]林丽艳,张慧云,何韶衡.IL-6及其受体与炎症性疾病关系的新进展[J].中国热带医学,2008,8(4):680-682.
[11] CAO C,YIN C,CHAI Y,et al. Ulinastatin mediates suppression of regulatory T cells through TLR4/NF-κB signaling pathway in murine sepsis[J]. Int Immunopharmacol,2018,64:411-423.
[12] TIAN Y, LI Z, SHEN B, et al. Protective effects of morin on lipopolysaccharide/d-galactosamine-induced acute liver injury by inhibiting TLR4/NF-κB and activating Nrf2/HO-1 signaling pathways[J]. Int Immunopharmacol,2017,45:148-155.
[2] VONK NOORDEGRAAF A, GROENEVELDT J A, BOGAARD H J. Pulmonary hypertension[J]. Eur Respir Rev,2016,25(139):4-11.
[3] DING G Z,LI W S. The expressions and significance of APN,D-D,IL-17 and hs-CRP in patients with acute exacerbation of chronic obstructive pulmonary disease[J].Eur Rev Med Pharmacol Sci,2018,22(19):6463-6468.
[4]郑静,张红芹,徐璐,等.乌司他丁辅助全身麻醉对合并慢性阻塞性肺疾病患者血清TNF-α、IL-6、IL-8水平的影响[J].川北医学院学报,2017,32(1):13-15.
[5] TRIPATHI P M,KANT S, YADAV R S, et al. Expression of toll-like receptor 2 and 4 in peripheral blood neutrophil cells from patients with chronic obstructive pulmonary disease[J]. Oman Med J,2017,32(6):477-485.
[6]慢性阻塞性肺疾病诊治指南(2013年修订版)[J].中国医学前沿杂志(电子版),2014,6(2):67-80.
[7] GORDEUK V R, CASTRO 0 L, MACHADO R F. Pathophysiology and treatment of pulmonary hypertension in sickle cell disease[J].Blood,2016,127(7):820-828.
[8]丁国良,钱萍艳,保瑀,等.小剂量对比剂快速扫描在肺动脉血管造影中的应用价值[J].江苏大学学报(医学版),2016,26(6):537-539.
[9] ARIAN A,MORTAZAVI MOGHADAM S G,KAZEMI T,et al. Trial of Atorvastatin on Serum Interleukin-6,Total Antioxidant Capacity,C-Reactive Protein, and Alpha-1 Antitrypsin in Patients with Chronic Obstructive Pulmonary Disease[J]. J Res Pharm Pract,2018,7(3):141-146.
[10]林丽艳,张慧云,何韶衡.IL-6及其受体与炎症性疾病关系的新进展[J].中国热带医学,2008,8(4):680-682.
[11] CAO C,YIN C,CHAI Y,et al. Ulinastatin mediates suppression of regulatory T cells through TLR4/NF-κB signaling pathway in murine sepsis[J]. Int Immunopharmacol,2018,64:411-423.
[12] TIAN Y, LI Z, SHEN B, et al. Protective effects of morin on lipopolysaccharide/d-galactosamine-induced acute liver injury by inhibiting TLR4/NF-κB and activating Nrf2/HO-1 signaling pathways[J]. Int Immunopharmacol,2017,45:148-155.