多囊卵巢综合征中 SFRP5 减少与代谢性炎症过度相关，二甲双胍可使其逆转：提示其在代谢失调中的作用。
Decreased SFRP5 correlated with excessive metabolic inflammation in polycystic ovary syndrome could be reversed by metformin: implication of its role in dysregulated metabolism.
机构信息
NHC Key Laboratory of Birth Defects and Reproductive Health, Chongqing Population and Family Planning Science and Technology Research Institute, Chongqing, People's Republic of China.
Reproductive Medicine Center, Department of Obstetrics and Gynecology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, People's Republic of China.
出版信息
J Ovarian Res. 2021 Jul 20;14(1):97. doi: 10.1186/s13048-021-00847-4.
BACKGROUND
Polycystic Ovary Syndrome (PCOS) is a complex endocrine disorder of heterogeneous nature. Secreted frizzled-related protein (SFRP) 5 is an anti-inflammatory adipokine implicated in metabolic homeostasis. We aimed to confirm the correlation between SFRP5, metabolic inflammation and PCOS, investigate the predictive value of SFRP5 for PCOS and the involvement of SFRP5 in metformin treated PCOS.
METHODS
This retrospective case-control study included 140 PCOS and 33 control women. Sixty seven PCOS women were included for detecting serum SFRP5 level and its correlation with metabolic inflammation. Predictive value of SFRP5 for PCOS was evaluated by logistic regression and receiver operating characteristic (ROC) analyses. Seventy three PCOS women complicated with impaired glucose tolerance (IGT)/insulin resistance (IR) were included for investigating the effects of metformin (37 with metformin vs. 36 without metformin) on SFRP5, pro-inflammatory cytokines, ovulation and pregnancy rate.
RESULTS
Plasma SFRP5 levels were decreased in PCOS (odds ratio: 0.78, 95% confidence interval (CI):0.703-0.866, P < 0.001) independent of obesity. SFRP5 was negatively associated with IL-6, TNFα, FAI and HOMA-IR. The cut-off point of SFRP5 < 46.13 ng/ml was optimal to identify PCOS with a higher specificity of 96.87% and a relatively lower sensitivity compared to AMH. SFRP5 increased specificity of AMH for predicting PCOS, especially which with relatively decreased AMH (< 4.7 ng/ml). Metformin promoted SFRP5 and decreased leptin, IL-6 and TNFα secretion in PCOS women with metabolic abnormality in a time dependent manner and with improved ovulation rate and pregnancy rate.
CONCLUSION
Decreased SFRP5 was associated with metabolic inflammation in PCOS and has a potential role for the supplement of AMH in predicting PCOS. The reverse of serum SFRP5 by metformin indicated that SFRP5 participated in the improvment of follicular development by metformin. Further prospective investigations are needed to confirm these preliminary data.
背景
多囊卵巢综合征（PCOS）是一种具有异质性的复杂内分泌疾病。卷曲相关蛋白 5（SFRP5）是一种具有抗炎作用的脂肪因子，与代谢稳态有关。我们旨在证实 SFRP5 与 PCOS 之间的相关性，研究 SFRP5 对 PCOS 的预测价值，以及 SFRP5 在二甲双胍治疗 PCOS 中的作用。
方法
本回顾性病例对照研究纳入了 140 例 PCOS 患者和 33 名对照女性。67 例 PCOS 患者用于检测血清 SFRP5 水平及其与代谢性炎症的相关性。通过逻辑回归和受试者工作特征（ROC）分析评估 SFRP5 对 PCOS 的预测价值。73 例 PCOS 患者合并糖耐量受损（IGT）/胰岛素抵抗（IR），其中 37 例接受二甲双胍治疗（37 例），36 例未接受二甲双胍治疗（36 例），用于研究二甲双胍对 SFRP5、促炎细胞因子、排卵率和妊娠率的影响。
结果
PCOS 患者血浆 SFRP5 水平降低（比值比：0.78，95%置信区间（CI）：0.703-0.866，P<0.001），与肥胖无关。SFRP5 与 IL-6、TNFα、FAI 和 HOMA-IR 呈负相关。SFRP5<46.13ng/ml 为最佳截断值，可特异性 96.87%、敏感性相对较低地识别 PCOS，优于 AMH。SFRP5 提高了 AMH 预测 PCOS 的特异性，特别是对于相对降低的 AMH（<4.7ng/ml）。二甲双胍可促进 PCOS 患者代谢异常时 SFRP5 的分泌，并呈时间依赖性降低瘦素、IL-6 和 TNFα 的分泌，从而提高排卵率和妊娠率。
结论
SFRP5 在 PCOS 中与代谢性炎症有关，可能对 AMH 预测 PCOS 具有补充作用。二甲双胍逆转血清 SFRP5 表明 SFRP5 参与了二甲双胍改善卵泡发育的过程。需要进一步的前瞻性研究来证实这些初步数据。
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