多囊卵巢综合征痰湿证患者血清miRNA-93的表达及意义
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摘要
目的:分析多囊卵巢综合征痰湿证患者生殖内分泌、糖脂代谢特征及血清中miRNA-93的表达差异,探讨多囊卵巢综合征痰湿证形成机理。方法:选取行体外受精-胚胎移植的不孕患者共44例,其中多囊卵巢综合征痰湿证患者15例(痰湿组)、多囊卵巢综合征非痰湿证患者14例(非痰湿组)、男方因素不孕症患者15例(对照组)。采用实时荧光定量PCR检测患者血清中miRNA-93的表达差异,分析比较3组患者临床资料、实验室指标和血清miRNA-93表达水平的差异。结果:①痰湿组BMI、WHR水平高于非痰湿组患者(P<0.05)。②痰湿组LH、T、HOMA-IR、HDL-C水平较对照组具有显著性差异(P<0.05);非痰湿组LH水平较对照组显著升高(P<0.05);与非痰湿组比较,痰湿组HOMA-IR、TC、TG、HDL-C、LDL-C水平具有显著性差异(P<0.05)。③3组间血清miRNA-93表达水平具有显著性差异(P<0.05),PCOS患者较对照组表达水平显著升高(P<0.05),PCOS痰湿组较非痰湿组miRNA-93表达亦具有显著性差异(P<0.05)。结论:miRNA-93在多囊卵巢综合征患者,尤其是痰湿证患者血清中特异性高表达,可能参与了多囊卵巢综合征痰湿证的发病过程。
Objective: To research the difference of serum miRNA-93 expression in polycystic ovary syndrome(PCOS) patients with phlegm dampness syndromeand study the pathogenesis of phlegm dampness syndrome in polycystic ovary syndrome(PCOS). Methods: Forty-four patients underwent in vitro fertilization and embryo transfer were enrolled to this study, including 15 polycystic ovary syndrome patients with phlegm dampness syndrom(phlegm dampness group),14 polycystic ovary syndrome patients with non-phlegm dampness syndrome(non-phlegm dampness group) and 15 patients with male factor infertility(control group). Real-time fluorescence quantitative PCR was used to detect the miRNA-93 expression in serum, and the differences of clinical and laboratory data in three groups were also analyzed. Results:①BMI and WHR in phlegm dampness group were higher than those in the non-phlegm dampness group(P<0.05). ②There was significant difference in LH, T, HOMA-IR and HDL-C levels between the phlegm dampness group and the control group(P<0.05). Compared to the control group, LH level in non-phlegm dampness group was increased(P<0.05). The levels of HOMA-IR,TC,TG and LDL-C were significant higher in the phlegm dampness group than that in the non-phlegm dampness group(P<0.05). ③There was significant difference in the level of serum miRNA-93 among three groups. Compared to the control group and the non-phlegm dampness group, the level of serum miRNA-93 was increased in the phlegm dampness group(P<0.05). Conclusion:The miRNA-93 was higher expressed in the serum of PCOS patients, especially in patients with phlegm dampness syndrome and it may be involved in the pathogenesis of phlegm dampness syndrome in polycystic ovary syndrome.
Objective: To research the difference of serum miRNA-93 expression in polycystic ovary syndrome(PCOS) patients with phlegm dampness syndromeand study the pathogenesis of phlegm dampness syndrome in polycystic ovary syndrome(PCOS). Methods: Forty-four patients underwent in vitro fertilization and embryo transfer were enrolled to this study, including 15 polycystic ovary syndrome patients with phlegm dampness syndrom(phlegm dampness group),14 polycystic ovary syndrome patients with non-phlegm dampness syndrome(non-phlegm dampness group) and 15 patients with male factor infertility(control group). Real-time fluorescence quantitative PCR was used to detect the miRNA-93 expression in serum, and the differences of clinical and laboratory data in three groups were also analyzed. Results:①BMI and WHR in phlegm dampness group were higher than those in the non-phlegm dampness group(P<0.05). ②There was significant difference in LH, T, HOMA-IR and HDL-C levels between the phlegm dampness group and the control group(P<0.05). Compared to the control group, LH level in non-phlegm dampness group was increased(P<0.05). The levels of HOMA-IR,TC,TG and LDL-C were significant higher in the phlegm dampness group than that in the non-phlegm dampness group(P<0.05). ③There was significant difference in the level of serum miRNA-93 among three groups. Compared to the control group and the non-phlegm dampness group, the level of serum miRNA-93 was increased in the phlegm dampness group(P<0.05). Conclusion:The miRNA-93 was higher expressed in the serum of PCOS patients, especially in patients with phlegm dampness syndrome and it may be involved in the pathogenesis of phlegm dampness syndrome in polycystic ovary syndrome.
引文
[1] 徐琬梨.多囊卵巢综合征中医证素分布及组合规律的文献研究[J]. 中华中医药杂志, 2013, 28(9):2720-2722.
[2] Anja Elaine S?rensen, Marie Louise Wissing, Sofia Sal?, et al. MicroRNAs Related to Polycystic Ovary Syndrome (PCOS) [J]. Genes (Basel), 2014, 5(3): 684-708.
[3] Jiang L,Huang J,Li L,et al.MicroRNA-93 promotes ovarian granulosa cells proliferation through targeting CDKN1A in polycystic ovarian syndrome[J].J Clin Endocrinol Metab, 2015, 100(5): E729-E738.
[4] Roth LW, McCallie B, Alvero R, et al. Altered microRNA and gene expression in the follicular fluid of women with polycystic ovary syndrome[J]. J Assist Reprod Genet, 2014, 31(3): 355-362.
[5] Sang Q, Yao Z, Wang H, et al. Identification of microRNAs in human follicular fluid: characterization of microRNAs that govern steroidogenesis in vitro and are associated with polycystic ovary syndrome in vivo[J]. J Clin Endocrinol Metab, 2013, 98(7): 3068-3079.
[6] Xu B, Zhang YW, Tong XH, et al. Characterization of microRNA profile in human cumulus granulosa cells: Identification of microRNAs that regulate Notch signaling and are associated with PCOS[J]. Mol Cell Endocrinol, 2015, 404C:26-36.
[7] Lin L, Du T, Huang J, et al. Identification of Differentially Expressed MicroRNAs in the Ovary of Polycystic Ovary Syndrome with Hyperandrogenism and Insulin Resistance[J]. Chin Med J (Engl), 2015, 128(2): 169-174.
[8] Fernandez-Valverde SL, Taft RJ, Mattick JS. MicroRNAs in β-cell biology,insulin resistance, diabetes and its complications[J]. Diabetes, 2011, 60(7):1825-1831.
[9] Chen YH,Heneidi S,Lee JM,et al. miRNA-93 Inhibits GLUT4 and Is Overexpressed in Adipose Tissue of Polycystic Ovary Syndrome Patients and Women With Insulin Resistance[J]. Diabetes, 2013, 62(7): 2278-2286.
[10] Murri M, Insenser M, Fernández-Durán E, et al. Effects of polycystic ovary syndrome (PCOS), sex hormones, and obesity on circulating miRNA-21, miRNA-27b, miRNA-103, and miRNA-155 expression[J]. J Clin Endocrinol Metab, 2013, 98(11): 1835-1844.
[11] Sathyapalan T, David R, Gooderham NJ, et al. Increased expression of circulating miRNA-93 in women with polycystic ovary syndrome may represent a novel, non-invasive biomarker fordiagnosis[J].Sci Rep, 2015,19(5):16890.
[12] 刘燕,李博.多囊卵巢综合征外周血miRNA-93的表达及作用意义[J].中国优生与遗传杂志, 2017, 25(9): 57-59.
[13] 张副兴, 管斯琪, 丁彩飞. 痰湿型多囊卵巢综合征进展[J].黑龙江中医药, 2015,44(1):80-82.
[14] Rotterdam ESHRE/ASRM-Sponsored PCOS consensus workshop group. Revised 2003 consensus on diagnostic criteria and long term health risks related to polycystic ovary syndrome (PCOS[J]. Hum Reprod,2004,19(1): 41-47.
[15] 张玉珍. 中医妇科学[M]. 北京:中国中医药出版社,2007:121-130.
[16] 郑筱萸. 中药新药临床研究指导原则[S]. 北京:中国医药科技出版社,2002:385-389.
[17] 徐莉, 谢波, 徐丹, 等. 多囊卵巢综合征中医证型分布规律及糖代谢特点研究[J]. 实用中医药杂志, 2011,27(6):374-375.
[18] 张洪芳, 龚瑾. 中医药治疗痰湿型多囊卵巢综合征体会[J].河南中医, 2014, 34(6): 1150-1151.
[19] 洪雅冰. 小议痰湿型多囊卵巢综合征的治疗[J]. 天津中医药大学学报, 2013, 32(3): 181-182.
[20] 苏庆民.肥胖人的体质研究[J].中医杂志,1992(1):33-49.
[21] 高金金, 侯丽辉. 李妍多囊卵巢综合征痰湿证患者糖代谢的临床研究[J]. 中华中医药学刊, 2017,35(3): 615-617.
[22] 鲁雅娟,张秀,王佩娟,等.痰湿与多囊卵巢综合征关系的理论探讨[J].浙江中医药大学学报,2016,40(9):657-665.
[23] 刘东平, 徐海燕. 多囊卵巢综合征证治特色[J]. 河北中医,2011, 33(4):539-541.
[24] 李晓倩, 沈山梅, 顾勇清, 等. 多囊卵巢综合征痰湿证患者内分泌特征研究[J]. 中华中医药学刊, 2015, 33(7):1733-1735.
[25] Hwang HW, Mendell JT. MicroRNAs in cell proliferation, cell death, and tumorigenesis[J]. Br J Cancer, 2006, 94(6): 776-780.
[26] Long W, Zhao C, Ji C, et al. Characterization of serum microRNAs profile of PCOS and identification of novel non-invasive biomarkers[J]. Cell Physiol Biochem, 2014, 33(5): 1304-1315.
[27] Ding CF, Chen WQ, Zhu YT, et al. Circulating microRNAs in patients with polycystic ovary syndrome[J]. Hum Fertil (Camb),2014, 30:1-8.
[28] 杨阳, 张运津, 谢安,等.糖尿病肾病患者血清mi RNA-93的表达变化及意义[J].实验与检验医学,2012, 30(3):222-224.
[29] Larance M,Ramm G,James DE. The GLUT4 code [J]. Mol Endocrinol,2008,22(2):226-233.
[30] Chen X. The influence of androgens on the development of insulin resistance in polycystic ovary syndrome and its molecular mechanisms[D]. Shanghai:Fudan University, 2006.
[31] Wang W, Hao GM, Li XD, et al. The effects of insulin and testosterone on the expression of GLUT4 in Ishikawa cell[J]. J Reprod Med,2008,17(3):196-201.
[32] 邢莹莹,李青春,韩艳艳,等. 循环miRNA-93在DHEA 多囊卵巢综合征大鼠模型中的表达及其意义[J]. 现代妇产科进展, 2017, 26(12):911-916.
[2] Anja Elaine S?rensen, Marie Louise Wissing, Sofia Sal?, et al. MicroRNAs Related to Polycystic Ovary Syndrome (PCOS) [J]. Genes (Basel), 2014, 5(3): 684-708.
[3] Jiang L,Huang J,Li L,et al.MicroRNA-93 promotes ovarian granulosa cells proliferation through targeting CDKN1A in polycystic ovarian syndrome[J].J Clin Endocrinol Metab, 2015, 100(5): E729-E738.
[4] Roth LW, McCallie B, Alvero R, et al. Altered microRNA and gene expression in the follicular fluid of women with polycystic ovary syndrome[J]. J Assist Reprod Genet, 2014, 31(3): 355-362.
[5] Sang Q, Yao Z, Wang H, et al. Identification of microRNAs in human follicular fluid: characterization of microRNAs that govern steroidogenesis in vitro and are associated with polycystic ovary syndrome in vivo[J]. J Clin Endocrinol Metab, 2013, 98(7): 3068-3079.
[6] Xu B, Zhang YW, Tong XH, et al. Characterization of microRNA profile in human cumulus granulosa cells: Identification of microRNAs that regulate Notch signaling and are associated with PCOS[J]. Mol Cell Endocrinol, 2015, 404C:26-36.
[7] Lin L, Du T, Huang J, et al. Identification of Differentially Expressed MicroRNAs in the Ovary of Polycystic Ovary Syndrome with Hyperandrogenism and Insulin Resistance[J]. Chin Med J (Engl), 2015, 128(2): 169-174.
[8] Fernandez-Valverde SL, Taft RJ, Mattick JS. MicroRNAs in β-cell biology,insulin resistance, diabetes and its complications[J]. Diabetes, 2011, 60(7):1825-1831.
[9] Chen YH,Heneidi S,Lee JM,et al. miRNA-93 Inhibits GLUT4 and Is Overexpressed in Adipose Tissue of Polycystic Ovary Syndrome Patients and Women With Insulin Resistance[J]. Diabetes, 2013, 62(7): 2278-2286.
[10] Murri M, Insenser M, Fernández-Durán E, et al. Effects of polycystic ovary syndrome (PCOS), sex hormones, and obesity on circulating miRNA-21, miRNA-27b, miRNA-103, and miRNA-155 expression[J]. J Clin Endocrinol Metab, 2013, 98(11): 1835-1844.
[11] Sathyapalan T, David R, Gooderham NJ, et al. Increased expression of circulating miRNA-93 in women with polycystic ovary syndrome may represent a novel, non-invasive biomarker fordiagnosis[J].Sci Rep, 2015,19(5):16890.
[12] 刘燕,李博.多囊卵巢综合征外周血miRNA-93的表达及作用意义[J].中国优生与遗传杂志, 2017, 25(9): 57-59.
[13] 张副兴, 管斯琪, 丁彩飞. 痰湿型多囊卵巢综合征进展[J].黑龙江中医药, 2015,44(1):80-82.
[14] Rotterdam ESHRE/ASRM-Sponsored PCOS consensus workshop group. Revised 2003 consensus on diagnostic criteria and long term health risks related to polycystic ovary syndrome (PCOS[J]. Hum Reprod,2004,19(1): 41-47.
[15] 张玉珍. 中医妇科学[M]. 北京:中国中医药出版社,2007:121-130.
[16] 郑筱萸. 中药新药临床研究指导原则[S]. 北京:中国医药科技出版社,2002:385-389.
[17] 徐莉, 谢波, 徐丹, 等. 多囊卵巢综合征中医证型分布规律及糖代谢特点研究[J]. 实用中医药杂志, 2011,27(6):374-375.
[18] 张洪芳, 龚瑾. 中医药治疗痰湿型多囊卵巢综合征体会[J].河南中医, 2014, 34(6): 1150-1151.
[19] 洪雅冰. 小议痰湿型多囊卵巢综合征的治疗[J]. 天津中医药大学学报, 2013, 32(3): 181-182.
[20] 苏庆民.肥胖人的体质研究[J].中医杂志,1992(1):33-49.
[21] 高金金, 侯丽辉. 李妍多囊卵巢综合征痰湿证患者糖代谢的临床研究[J]. 中华中医药学刊, 2017,35(3): 615-617.
[22] 鲁雅娟,张秀,王佩娟,等.痰湿与多囊卵巢综合征关系的理论探讨[J].浙江中医药大学学报,2016,40(9):657-665.
[23] 刘东平, 徐海燕. 多囊卵巢综合征证治特色[J]. 河北中医,2011, 33(4):539-541.
[24] 李晓倩, 沈山梅, 顾勇清, 等. 多囊卵巢综合征痰湿证患者内分泌特征研究[J]. 中华中医药学刊, 2015, 33(7):1733-1735.
[25] Hwang HW, Mendell JT. MicroRNAs in cell proliferation, cell death, and tumorigenesis[J]. Br J Cancer, 2006, 94(6): 776-780.
[26] Long W, Zhao C, Ji C, et al. Characterization of serum microRNAs profile of PCOS and identification of novel non-invasive biomarkers[J]. Cell Physiol Biochem, 2014, 33(5): 1304-1315.
[27] Ding CF, Chen WQ, Zhu YT, et al. Circulating microRNAs in patients with polycystic ovary syndrome[J]. Hum Fertil (Camb),2014, 30:1-8.
[28] 杨阳, 张运津, 谢安,等.糖尿病肾病患者血清mi RNA-93的表达变化及意义[J].实验与检验医学,2012, 30(3):222-224.
[29] Larance M,Ramm G,James DE. The GLUT4 code [J]. Mol Endocrinol,2008,22(2):226-233.
[30] Chen X. The influence of androgens on the development of insulin resistance in polycystic ovary syndrome and its molecular mechanisms[D]. Shanghai:Fudan University, 2006.
[31] Wang W, Hao GM, Li XD, et al. The effects of insulin and testosterone on the expression of GLUT4 in Ishikawa cell[J]. J Reprod Med,2008,17(3):196-201.
[32] 邢莹莹,李青春,韩艳艳,等. 循环miRNA-93在DHEA 多囊卵巢综合征大鼠模型中的表达及其意义[J]. 现代妇产科进展, 2017, 26(12):911-916.