多囊卵巢综合征患者多普勒超声测量参数与性激素、炎性因子水平的相关性分析.pdf

CorrT临床研究。594BME&ClinMed,eptember2023,Vol.27,No.5生物医学工程与临床2 0 2 3年9 月第2 7 卷第5期网络出版时间：2 0 2 3-0 8-2 2 17：0 4：33D0I：10.13339/j.c n k i.s g l c.2 0 2 30 8 2 2.0 15网络出版地址：https:/ 0 例（病例组），年龄2 335岁，平均年龄30.6 9 岁。另取同期在医院体检健康女性10 0 例（对照组），年龄2235岁,平均年龄30.2 5岁。给予两组多普勒超声检查,测量两组子宫、卵巢血流参数 阻力指数(RI)、搏动指数(PI),并取肘静脉血检测其性激素 雌二醇(E2)、促卵泡激素(FSH)、促黄体生成素(LH)、睾酮(T)及炎性因子 肿瘤坏死因子(TNF)-、白细胞介素6(IL-6)、内皮抑素(ES)水平,分析PCOS 患者多普勒超声血流参数与其血清炎性因子、性激素水平的相关性。结果两组超声参数比较，病例组子宫RI、PI显著高于对照组（0.8 9 0.14us0.810.12、2.8 7 0.2 6 v s2.140.21。P 0.0 5)，卵巢RI、PI显著低于对照组(0.430.0 7 vs0.620.12、0.7 30.11v s 0.9 10.14。P 0.0 5）。病例组血清LH、T 水平显著高于对照组(9.331.6 4）U/Lvs（4.59 1.0 2）U/L、（1.140.13）n g/mLv s（0.6 10.0 8）n g/mL。P0.05,FSH水平显著低于对照组(6.311.0 2 U/Lus（8.9 6 1.2 8）U/L。P0.05)。病例组血清TNF-、IL-6、E S 均显著高于对照组 2 0.9 53.0 5）ng/mLvs（12.52 2.51）n g/mL、（12.541.57）n g/mLv s(6.331.05）p g/mL、2 34.2 516.33）g/Lvs（156.9 7 17.0 5）g/L。P 0.0 5。PC O S 患者子宫RI、PI与患者LH、T 水平正相关（r=0.531、0.433、0.37 1、0.40 7,均P0.05)，与FSH水平负相关（r=-0.963、-1.0 8 1,P 0.0 5)；卵巢RI、PI与患者血清LH、T 水平负相关（r=-2.082、-1.2 14、-1.530、-1.0 9 4,均P0.05），与FSH水平正相关（r=0.392、0.58 3,均P0.05);PCOS患者子宫RI、PI与血清TNF-、IL-6、E S 均为正相关（r=0.364、0.56 1、0.38 5、0.2 6 9、0.312、0.40 5，均P0.05），卵巢RI、PI与血清TNF-、IL-6、E S 均为负相关（r=-2.634、-3.39 7、-1.48 2、-0.39 8、-1.433、-2.317，均P0.05)。结论PCOS患者普遍存在子宫及卵巢血流动力学异常,并伴有炎性因子及部分性激素水平高表达,其子宫、卵巢多普勒超声参数与性激素、炎性因子水平具有相关性，关键词：多囊卵巢综合征；多普勒超声；性激素；炎性因子；相关性分析中图分类号:R711.75;R445.1文献标识码：A文章编号：10 0 9-7 0 9 0(2 0 2 3)0 5-0 59 4-0 5Correlation analysis of Doppler ultrasonography parameters with serum levels of sex hormones and inflammatorCorrelation analysis of Doppler ultrasonography parameters with serum levels of sex hormones and inflammatoryfactors inpatients with polycystic ovary syndromeZHAO Fang-yuan,ZOU Hong,SHI Si-maob,XU Fangb（afactors in patients with polycystic ovary syndromeZHAO Fang-yuan,ZOU Hong,SHI Si-maob,XU Fangh(a.DepartmentofIlltrondMedicine:b.DeparttofCTheFirstAffiliated Hospital of HeilonsIniversPOyCaiigyuanr11011811aoAo1agepartment of Ultrasound Medicine;b.Department of Gynecology,The First Affliated Hospital of Heilongjiang University ofraditional Chinese Medicine,Harbin150040,Heilongjiang,China)esponding author:XU Fang.E-mail:.Abstract:Objective To explore the correlation between Doppler ultrasound measurement parameters and serum levels of sexhormones and inflammatory factors in patients with polycystic ovary syndrome(PCOS).Methods A total of 120 patients withPCOS were enrlled as case group,which aged 23-35 years old with mean age of 30.69 years old.At the same period,100healthy examined females were set as control group,aged 22-35 years old with mean age of 30.25 years old.All of them per-formed Doppler ultrasonography to measure uterine and ovarian blood flow parametersresistance index(RI),pulsatility index(PI),and underwent elbow venous blood examination to detect serum levels of sex hormoneestradiol(E2),follicle stimulatinghormone(FSH),luteinizing hormone(LH),testosterone(T)and inflammatory factorstumor necrosis factor(TNF)-,interleukin-6(IL-6),endostatin(ES)levels.The correlation between Doppler ultrasound blood flow parameters and serum inflammatory factorsas well as sex hormone levels in PCOS patients was analyzed.Results The uterine RI and PI in case group were significantlyhigher than those in control group(0.89 0.14 us 0.81 0.12,2.87 0.26 vs 2.14 0.21.P 0.05),while ovarian RI and PI incase group were significantly lower than in control group(0.43 0.07 vs 0.62 0.12,0.73 0.11 vs 0.91 0.14.P0.05).Thelevels of serum LH and T in case group were significantly higher than those in control group(9.33 1.64)U/L us(4.59 1.02)U/L,作者单位：黑龙江中医药大学附属第一医院a.超声医学科；b.妇科，黑龙江哈尔滨150 0 40作者简介：赵芳园(19 8 2）,女，黑龙江省人，硕士，主治医师，主要从事妇科超声诊断与治疗工作。电话：158 46 6 2 0 0 7 7。E-mail;。基金项目：黑龙江省中医药科研项目(2 0 18-0 6 4)；国家自然科学基金资助项目(8 2 0 0 440 1)通信作者：徐芳（19 8 1），女，黑龙江尚志市人，博士，副主任医师，主要从事妇科疾病治疗工作。电话：150 8 46 6 2 7 18。E-mail：x u 150 8 46 6 2 7 18 16 o版权保护，不得翻录。595-生物医学工程与临床2 0 2 3年9 月第2 7 卷第5期BME&ClinMed,September2023,Vol.27,No.5(1.14 0.13)ng/mL vs(0.61 0.08)ng/mL.P 0.05,while FSH level of in case group was significantly lower than that ofcontrol group(6.31 1.02)U/L vs(8.96 1.28)U/L.P 0.05).The serumlevels of TNF-,IL-6 and ES in case group were significantly higher than those in control group(20.95 3.05)ng/mL vs(12.52 2.51)ng/mL,(12.54 1.57)pg/mL vs(6.33 1.05)pg/mL,(234.25 16.33)g/L vs(156.97 17.05)g/L.P 0.05).The uter-ine RI and PI of PCOS patients were positively significantly correlated with LH and T levels(r=0.531,0.433,0.371,0.407,P0.05),and were negatively significantly correlated with FSH level(r=-0.963,-1.081.P 0.05).In PCOS patients,the ovarianRI and PI were negatively correlated with serum LH and T levels(r=-2.082,-1.214,-1.530,-1.094.P 0.05),and was posi-tively correlated with serum FSH level(r=0.392,0.583.P 0.05).The uterine RI and PI were positively correlated with serumTNF-,IL-6 and ES in PCOS patients(r=0.364,0.561,0.385,0.269,0.312,0.405.P 0.05),ovarian RI and PI were negativelycorrelated with serum TNF-,IL-6 and ES(r=-2.634,-3.397,-1.482,-0.398,-1.433,-2.317.P0.05)。医院伦理委员会已批准此次研究（批号：201904-09)。1.2方法1.2.1多普勒超声检查应用美国GE公司生产的Voluson-E10彩色多普勒超声系统进行超声诊断，探头频率设置为7.5MHz。研究对象取仰卧位接受检查，经阴道探查，探头缓慢推人阴道，对其卵巢间质中及子宫峡部两侧最强血流信号进行检测。计算子宫、卵巢动脉阻力指数(resis-tance index,RI)及搏动指数(pulsatility index,PI)。1.2.2性激素及炎性因子水平检测于清晨空腹状态采集肘静脉血4mL。离心分离血清（转速30 0 0 r/min，时间15min），利用酶联免疫吸附分析(enzyme-linked immunosorbent assay,ELISA)法测量炎性因子 TNF-、IL-6、E S)及性激素 雌二醇(estradiol,E2)、促卵泡激素(follicle stimulating hor-mone,FSH)、促黄体生成素(luteining hormone,LH)、睾酮(testosterone,T)水平。相关试剂盒均购自中国武汉菲恩生物科技有限公司，检测步骤严格按照试剂盒上操作说明进行。596-BME&ClinMed,September 2023,Vol.27,No.5生物医学工程与临床2 0 2 3年9 月第2 7 卷第5期1.2.3观察指标比较两组子宫及卵巢RI、PI 及血清炎性因子(TNF-、IL-6、E S)、性激素(LH、F S H、T、E 2)水平,并对各多普勒超声血流参数与血清炎性因子、性激素的相关性进行分析。1.3统计学方法使用SPSS24.0软件分析数据。血流参数、炎性因子及性激素水平等计量资料符合正态分布，以均数标准差表示，组间比较行独立样本t检验。血流参数与血清炎性因子、性激素水平相关性分析采用Pear-son 相关性分析。P0.05为差异有统计学意义,P0.01为差异有显著统计学意义。2结果2.1两组超声血流参数对比病例组子宫RI、PI显著高于对照组，卵巢 RI、PI显著低于对照组,差异有显著统计学意义(P0.01)。见表1。表1病例组与对照组子宫及卵巢RI、PI比较Tab.1Comparison of RI and PI of uterus and ovary between case group and control group子宫卵巢项目例数RIPIRIPI对照组1000.81 0.122.14 0.210.62 0.120.91 0.14病例组1200.89 0.142.87 0.260.43 0.070.73 0.11t一4.50023.03713.97310.447P0.0000.0000.0000.000一2.2两组血清炎性因子水平比较病例组血清TNF-、IL-6、E S 均显著高于对照组(20.95 3.05)ng/mL vs(12.52 2.51)ng/mL(12.54 1.57)pg/mL vs(6.33 1.05)pg/mL、(2 34.2 5 16.33)g/L vs(156.97 17.05)g/L。t =2 2.0 9 7、33.755、44.0 16 1,差异有统计学意义（P0.05）2.3两组性激素水平对比病例组 LH、T 水平均显著高于对照组,FSH水平显著低于对照组,差异有显著统计学意义(P0.05)。见表2。表2 病例组与对照组LH、F S H、E 2、T 水平比较Tab.2Comparison of LH,FSH,E2,T levels between case group and control group项目例数E2/pg/mLLH/U/LT/ng/mLFSH/U/L对照组10047.96 5.334.59 1.020.61 0.088.96 1.28病例组12048.58 5.419.33 1.641.14 0.136.31 1.02t0.85225.13035.53817.316一P0.3950.0000.0000.0002.4PCOS患者血流参数与血清炎性因子、性激素水平相关性分析经Pearson相关性分析提示,PCOS患者子宫RI、PI与血清TNF-、E S、IL-6 均为正相关(r=0.364、0.38 5、0.312、0.56 1、0.2 6 9、0.40 5,均P0.05）,卵巢RI、PI与血清TNF-、E S、IL-6 均为负相关(r=-2.634、-1.48 2、-1.433、-3.39 7、-0.39 8、-2.317,均P0.05)。PC O S 患者子宫RIPI与LH、T 水平正相关(r=0.531、0.4330.37 1、0.407,均P0.05),与FSH水平负相关(r=-0.963、-1.081,均P0.05）,卵巢RI、PI与LH、T 水平负相关(r=-2.082、-1.2 14、-1.530、-1.0 9 4,均P0.05),与FSH水平正相关(r=0.392、0.58 3,均P0.05)。见表3。表3PCOS患者子宫及卵巢RI、PI与其血清炎性因子、性激素水平相关性分析Tab.3Correlation analysis of uterine and ovarian RI and PI with serum inflammatory factors and sex hormone levels in PCOS patientsTNF-ESIL-6LHTFSH多普勒超声PPTPPPP子宫RI0.3640.0140.3850.0160.3120.0190.531 0.0010.3710.016-0.9630.014子宫PI0.5610.0030.269 0.0250.4050.0050.433 0.0710.4070.009-1.0810.009卵巢RI-2.6340.001-1.4820.0051.4330.002-2.0820.031-1.5300.0090.3920.021卵巢PI-3.3970.011-0.3980.013-2.3170.017-1.2140.029-1.0940.0140.5830.001597生物医学工程与临床2 0 2 3年9 月第2 7 卷第5期BME&Clin Med,September 2023,Vol.27,No.53讨论PCOS具体病因未明，目前已知其与遗传、内分泌紊乱等具有密切关联，是导致女性不孕的重要原因之一。鉴于该病发生后对女性生殖能力的影响,及早诊断并治疗是改善患者病情、提高其生存质量的关键。既往关于PCOS患者性激素水平的研究发现,此类患者普遍存在LH、T 水平过高,FSH水平过低现象,并指出利用此类血清学指标也可对PCOS患者进行辅助诊断及病情严重程度评估门。关于PCOS对性激素影响的作用机制,有学者认为可能与该病引起的代谢异常易导致卵泡微环境异常有关,微环境改变影响卵母细胞发育,诱使LH及T分泌增加,FSH分泌减少,进而抑制卵泡正常发育 8 。超声检查是目前PCOS诊断中最常用的影像学检查技术，其具有无创、便捷、可重复性高等优点，可直观了解患者卵巢、子宫形态及血流变化。但是常规下腹部超声检查易受患者肠气、腹部脂肪影响，出现漏诊、误诊情况，遂此次以经阴道超声进行检查，以提高检查质量。在笔者研究两组受试对象子宫及卵巢血流动力学分析中，病例组子宫RI、PI均显著高于对照组，卵巢RI、PI均显著低于对照组(P0.05),说明PCOS患者较健康女性其子宫及卵巢血流动力学改变明显，该利用多普勒超声检查可对此类患者进行有效诊断。笔者认为PCOS患者的激素水平异常可抑制卵泡发育,并增加小卵泡数量,诱使子宫RI、PI 增加,卵巢RI、PI 降低9。在性激素与多普勒超声血流参数的相关性分析中PCOS患者的子宫、卵巢RI及PI与其T、LH、F S H 均有相关性(P0.05),此观察结果也证实了上述观点。PCOS的发生、发展过程中,除患者伴有性激素水平异常外，多种炎性因子表达水平上调明显 10 。TNF-是生物活性广泛的促炎因子，其不仅可促使卵泡膜-间质细胞调亡，也可影响卵巢产生雄激素，诱使高雄性激素血症发生 1,12 ;IL-6作为IL成员之一，其表达水平与机体胰岛素抵抗具有相关性，可与TNF-共同作用,加重PCOS患者病情发展 3;ES为血管内皮细胞增殖的强力抑制因子,ES高表达可抑制PCOS患者体内血管内皮生长因子刺激血管新生，改变卵巢微环境,进一步加重患者病情 14,15。此次观察中病例组上述3项炎性因子水平显著高于对照组(P0.05)，也证实了TNF-、IL-6、E S 参与了PCOS的发生、发展。后续相关性分析中提示PCOS患者子宫及卵巢RI、PI 与其血清TNF-及、IL-6、E S 水平具有相关性(P0.05)。笔者认为 PCOS 患者子宫 RI、PI升高,卵巢 RI、PI降低提示其子宫、卵巢微环境改变，子宫 RI、PI 越高及卵巢 RI、PI 越低表明患者局部炎症越严重,因而通过多普勒超声检测患者子宫、卵巢血流动力学情况也有利此类患者病情严重的程度评估 16。但是，此次研究纳入样本量不大，且未考察此类患者其他超声测量参数与正常女性的差异，需在后续研究完善。综上所述,PCOS子宫、卵巢血流动力学与正常女性有显著差异，且其子宫、卵巢血流动力学异常与性激素、炎性因子表达水平异常具有相关性，多普勒超声检查可用于此类患者的诊断及病情评估。参考文献：【1 袁怡清,王丹瑾.多囊卵巢综合征的研究进展 1.贵州医药,2 0 2 0,44(7):10 41-10 43.YUAN Yi-qing,WANG Dan-jin.Research progress of poly-cystic ovary syndromeJ.Guizhou Medical Journal,2020,44(7):1041-1043.【2 梅忆媛，谢青贞.多囊卵巢综合征合并代谢紊乱的炎症机制 .中国计划生育和妇产科,2 0 2 1,13(4)：2 0-2 3.MEI Yi-yuan,XIE Qing-zhen.Inflammatory mechanism ofpolycystic ovary syndrome complicated with metabolic disor-dersJ.Chinese Journal of Family Planning and Gynecotokol-0gy,2021,13(4):20-23.3 Zhou Y,Lv L,Liu Q,et al.Total flavonoids extracted fromNervilia Fordi function in polycystic ovary syndrome throughIL-6 mediated JAK2/STAT3 signaling pathwayJ.Biosci Rep,2018,39(1):BSR20181380-BSR20181380.4 J Wang J,Wu X.Effects of mitochondrial dysfunction on energymetabolism switch by HIF-1 signaling in granulosa cells ofpolycystic ovary syndromeJJ.Endokrynola 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