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子宫内膜异位症患者血清与腹腔液中CRP、IL—8、VEGF的表达及临床意义

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  [摘要] 目的 探讨子宫内膜异位症患者血清和腹腔液中C-反应蛋白(CRP)、白细胞介素-8(IL-8)、血管内皮生长因子(VEGF)的表达及其临床意义。 方法 收集2015年8月~2017年8月青海红十字医院收治的93例子宫内膜异位症患者(子宫内膜异位症组),根据美国生育协会评分标准(r-AFS)分期将其分为Ⅰ期(n = 19)、Ⅱ期(n = 25)、Ⅲ期(n = 28)、Ⅳ期(n = 21),并于同期随机选取60例子宫肌瘤患者(子宫肌瘤组)和60名健康体检者为对照(对照组)。采用酶联免疫吸附法检测各组血清和腹腔液中CRP、IL-8、VEGF水平。 结果 子宫内膜异位症组患者血清CRP、IL-8、VEGF水平均高于子宫肌瘤组、对照组(P < 0.05),子宫内膜异位症组患者腹腔液中CRP、IL-8、VEGF水平高于子宫肌瘤组(P < 0.05)。随着疾病分期的增加,子宫内膜异位症组患者血清、腹腔液中CRP、IL-8、VEGF水平呈逐渐增加趋势(P < 0.05)。经Pearson积矩相关分析,子宫内膜异位症组患者血清中CRP、IL-8、VEGF与r-AFS评分呈正相关(r = 0.639、0.712、0.655,P < 0.05),腹腔液CRP、IL-8、VEGF与r-AFS评分呈正相关(r = 0.682、0.764、0.670,P < 0.05)。CRP的ROC曲线下面积(AUC)为0.784,最佳截断值为12.23 mg/L,灵敏度、特异性分别为0.77、0.72,准确性为0.71;IL-8的AUC为0.884,最佳截断值为20.97 mg/L,灵敏度、特异性分别为0.82、0.76,准确性为0.78;VEGF的AUC为0.889,最佳截断值为175.34 pg/mL,灵敏度、特异性分别为0.82、0.78,准确性为0.80;CRP、IL-8、VEGF联合检测的AUC为0.931,灵敏度、特异性分别为0.92、0.85,准确性为0.89。 结论 子宫内膜异位症患者血清及腹腔液中CRP、IL-8、VEGF水平顯著升高,并且与病情进展呈正相关,早期联合检测有助于鉴别诊断子宫内膜异位症及评估病情严重程度。
  [关键词] 子宫内膜异位症;C-反应蛋白;白细胞介素-8;血管内皮生长因子
  [中图分类号] R711.71 [文献标识码] A [文章编号] 1673-7210(2019)04(c)-0089-05
  Expression of CRP, IL-8 and VEGF in serum and peritoneal fluid of patients with endometriosis and its significance
  WEI Shunying WANG Liehong QI Qingling WANG Qianyin WANG Yonghua JIA Jia
  Department of Gynaecology, Qinghai Red Cross Hospital, Qinghai Province, Xi′ning 810000, China
  [Abstract] Objective To explore the expression of C-reactive protein (CRP), interleukin-8 (IL-8) and vascular endothelial growth factor (VEGF) in serum and peritoneal fluid of patients with endometriosis and its clinical significance. Methods A total of 93 patients with endometriosis (endometriosis group) admitted to Qinghai Red Cross Hospital from August 2015 to August 2017 were divided into stage Ⅰ (n = 19), stage Ⅱ (n = 25), stage Ⅲ (n = 28) and stage Ⅳ (n = 21) according to the American Fertility Society (r-AFS). At the same time, 60 patients with uterine leiomyoma (uterine leiomyoma group) and 60 healthy volunteers as control group were randomly selected. The levels of CRP, IL-8 and VEGF in serum and peritoneal fluid was detected by enzyme-linked immunosorbent assay. Results The levels of serum CRP, IL-8 and VEGF in endometriosis group were higher than those in uterine leiomyoma group and control group (P < 0.05). The levels of CRP, IL-8 and VEGF in peritoneal fluid were higher than those in patients with uterine leiomyoma group (P < 0.05). With the increase of disease stages, the levels of CRP, IL-8 and VEGF in serum and peritoneal fluid in patients with endometriosis increased gradually (P < 0.05). Pearson moment correlation analysis showed that serum CRP, IL-8, VEGF was positively associated with r-AFS score (r = 0.639, 0.712, 0.655; P < 0.05), and which in peritoneal fluid was positively associated with r-AFS score (r = 0.682, 0.764, 0.670; P < 0.05). The area under ROC curve (AUC) of CRP was 0.784, the best cut-off value was 12.23 mg/L, the sensitivity and specificity was 0.77 and 0.72, respectively, and the accuracy was 0.71. The AUC of IL-8 was 0.884, the best cut-off value was 20.97 mg/L, the sensitivity and specificity was 0.82 and 0.76, respectively, and the accuracy was 0.78. The AUC of VEGF was 0.889, the best cut-off value was 175.34 pg/mL, the sensitivity and specificity were 0.82 and 0.78, respectively, and the accuracy was 0.80. The AUC of CRP, IL-8 and VEGF was 0.931, the sensitivity and specificity was 0.92 and 0.85, respectively, and the accuracy was 0.89. Conclusion The levels of CRP, IL-8 and VEGF in serum and peritoneal fluid of patients with endometriosis are significantly elevated and positively associated with the progression of the disease. Early detection of CRP, IL-8 and VEGF is helpful to differential diagnosis of endometriosis and to evaluate the severity of the disease.   [Key words] Endometriosis; C-reactive protein; Interleukin-8; Vascular endothelial growth factor
  子宫内膜异位症是指正常子宫内膜组织在子宫腔以外的卵巢、盆腔腹膜、子宫直肠陷凹等部位异常生长及浸润所致的病理改变,在育龄妇女中发病率为10%~15%[1-2]。报道显示[3],近25%的子宫内膜异位症患者早期无典型临床表现,患者需通过开腹或者腹腔镜方能确诊,漏诊率较高。早期诊断子宫内膜异位症并评估病情进展,对制订针对性治疗方案以改善预后具有重要意义。现有研究表明[4-5],子宫内膜细胞逆流并种植于腹腔间质,并诱发炎性反应及促进新生血管生成是子宫内膜异位症发病主要机制之一。C-反应蛋白(C reactive protein,CRP)、白细胞介素-8(interleukin-8,IL-8)是常见的炎症细胞因子,有研究表明[6-7],CRP和IL-8在子宫内膜异位症发病过程中发挥重要作用。血管内皮生长因子(vascular endothelial growth factor,VEGF)是促血管生成因子,通过特异性结合血管内皮生长因子可溶性受体-1(soluble vascular endothelial growth factor receptor-1,sVEGFR-1)而刺激血管内皮细胞,最终促进新生血管形成[8]。本研究通过检测血清及腹腔液中CRP、IL-8、VEGF水平,旨在探讨联合检测对子宫内膜异位症鉴别诊断中的价值及在病情进展过程中的作用。现报道结果如下:
  1 资料与方法
  1.1 一般资料
  收集2015年8月~2017年8月青海红十字医院妇科门诊收治的93例行腹腔镜手术的子宫内膜异位症患者为子宫内膜异位症组。纳入标准:①腹腔镜术后病理组织切片经2名病理医师确诊为子宫内膜异位症;②术前未接受过任何放化疗治疗。排除标准:①妊娠期及哺乳期的女性;②心功能不全者;③肝、肾功能障碍者;④平素经期不规律患者;⑤内分泌以及代谢性疾病等可能影响本研究结果的疾病患者;⑥急、慢性炎性反应性疾病患者;⑦自身免疫性疾病患者;⑧合并子宫肌瘤、子宫腺肌病、乳腺增生性疾病的患者;⑨纳入研究前3个月内服用过激素类药物治疗者;⑩恶性肿瘤患者。93例患者年龄25~46岁,平均(36.24±4.50)岁;体重指数(BMI)21~28 kg/m2,平均(24.51±2.23)kg/m2;孕次1~5次,平均(2.21±0.56)次;产次1~4次,平均(1.83±0.47)次。并于同期随机选取60例子宫肌瘤患者为子宫肌瘤组,60名健康体检者为对照组。其中子宫肌瘤组年龄22~38岁,平均(34.09±5.21)岁;BMI 20~27 kg/m2,平均(22.95±2.86)kg/m2;孕次0~5次,平均(2.01±0.49)次;产次0~4次,平均(1.59±0.50)次。对照组年龄21~42岁,平均(35.18±5.56)岁;BMI 21~28 kg/m2,平均(23.52±3.03)kg/m2;孕次1~4次,平均(2.16±0.50)次;产次0~5次,平均(1.68±0.46)次。各组年龄、BMI、孕次、产次等基线资料比较,差异无统计学意义(P > 0.05),具有可比性。采用美国生育协会(AFS)制定的评分标准[9]从病变累及部位、大小、侧别、粘连程度等进行评分,并根据积分将患者分为四期:Ⅰ期(1~5分)19例,Ⅱ期(6~15分)25例,Ⅲ期(16~40分)28例,Ⅳ期(>40分)21例。本研究所有研究對象及家属均签署知情同意书,且该研究获得医院医学伦理委员会的批准。
  1.2 方法
  抽取患者入院次日清晨5 mL空腹肘静脉血,健康体检者于体检当日抽取5 mL空腹肘静脉血,将血液标本在半径为30 cm的离心机中3000 r/min离心5 min,将血清标本置于-80℃环境下保存,留待检测。同时子宫内膜异位症和子宫肌瘤患者手术过程中均在腹腔镜辅助下以穿刺针抽取5 mL位于子宫膀胱陷凹与子宫直肠陷凹处的腹腔液,在室温环境下放置1 h,然后以3000 r/min的转速离心5 min,留取上清液,置于-80℃环境下保存,留待检测。采用酶联免疫吸附法测定腹腔液和血清标本中CRP、IL-8、VEGF水平,深圳晶美生物技术有限公司提供相应的试剂盒(生产批号:120215),检测过程中相关操作严格按照试剂盒上说明进行。
  1.3 统计学方法
  采用SPSS 21.0统计学软件进行数据分析,计量资料用均数±标准差(x±s)表示,多组独立样本的比较采用方差分析,两两比较采用LSD-t检验,两组独立样本的比较采用成组t检验;计数资料用率表示,组间比较采用χ2检验;采用Pearson积矩相关分析各指标间的相关性;绘制受试者工作特征曲线(ROC)评估血清CRP、IL-8、VEGF对子宫内膜异位症的诊断价值。以P < 0.05为差异有统计学意义。
  2 结果
  2.1 各组血清及腹腔液中CRP、IL-8、VEGF水平比较
  三组血清、腹腔液CRP、IL-8、VEGF水平经方差分析,差异有统计学意义(P < 0.05),其中子宫内膜异位症组患者血清CRP、IL-8、VEGF水平均高于子宫肌瘤组、对照组(P < 0.05),子宫内膜异位症组患者腹腔液CRP、IL-8、VEGF水平高于子宫肌瘤组(P < 0.05);子宫肌瘤组与对照组血清CRP、IL-8、VEGF水平比较,差异无统计学意义(P > 0.05)。见表1。
  2.2 子宫内膜异位症不同疾病分期患者血清及腹腔液中CRP、IL-8、VEGF水平比较
  子宫内膜异位症组不同疾病分期患者血清、腹腔液CRP、IL-8、VEGF水平经方差分析,差异有统计学意义(P < 0.05),随着疾病分期的增加,血清、腹腔液CRP、IL-8、VEGF水平呈逐渐增加趋势(P < 0.05)。见表2。
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