脂联素及其受体在多囊卵巢综合征子宫内膜表达的研究
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摘要
目的:探讨脂联素及其受体在多囊卵巢综合征患者子宫内膜表达及分布的变化与其高发子宫内膜增生症甚至癌变的关系。
方法:用酶联免疫吸附法(ELISA)测定PCOS患者38例(PCOS组)和正常妇女40例(正常对照组)血清性激素、促性腺激素、血脂血糖和胰岛素水平;应用逆转录-聚合酶链式反应(RT-PCR)和免疫组化(IHC)的方法检测脂联素及其受体在子宫内膜mRNA表达和蛋白分布;比较PCOS患者与正常对照妇女组脂联素及其受体在子宫内膜表达和分布的差异并寻找其相关影响因素。
结果:(1)血清学检测:PCOS组睾酮72.74±7.64ng/dl明显高于正常对照组36.61±6.20 ng/dl,P＜0.05;PCOS组FSH6.81±0.61 IU/E明显低于正常对照组8.49±0.92IU/L,P＜0.05;PCOS组LH 9.09±0.89 IU/L明显高于正常对照组4.55±0.72IU/L,P＜0.05;PCOS组胆固醇4.99±0.36mmol/L明显高于正常对照组3.63±0.16mmol/L,P＜0.05;PCOS组甘油三脂2.06±0.77mmol/L明显高于正常对照组1.13±0.15mmol/L,P＜0.05;PCOS组空腹胰岛素9.13±0.59mIU/L明显高于正常对照组6.52±0.73mIU/L,P＜0.05;余指标无明显差异。(2)RT-PCR扩增出Adipo,AdipoR1,AdipoR2基因,PCOS组及正常对照组均以AdipoR1为主,AdipoR1与AdipoR2表达量差异有统计学意义(p＜0.05);PCOS组AdipoR1 mRNA 0.91±0.1表达明显低于正常对照组1.13±0.19,差异有统计学意义(P＜0.05);PCOS组总脂联素受体mRNA 1.22±0.15明显低于正常对照组1.45±0.29(P＜0.05);PCOS患者AdipoR2和Adiponectin mRNA表达略低于正常对照组,但差异无统计学意义(P＞0.05)。(3)Spearman相关性分析显示,脂联素总受体mRNA表达量与FSH呈正相关(r=0.482,p＜0.05),AdipoR1mRNA表达与FINS呈负相关(r=-0.69,p＜0.05)。(4)PCOS组和正常对照组子宫内膜免疫组化AdipoR1和AdipoR2呈阳性,主要表达于腺体细胞膜表面。
结论:(1)PCOS患者子宫内膜存在Adiponectin,AdipoR1和AdipoR2在mRNA水平的表达,且以AdipoR1为主。其中AdipoR1和脂联素总受体较正常对照组表达量下降,可能参与了PCOS患者高发子宫内膜增生症甚至癌变的转化过程。(2)脂联素总受体mRNA水平表达量与FSH呈正相关,而AdipoR1与FINS呈负相关。(3)PCOS和正常子宫内膜存在AdipoR1和AdipoR2蛋白水平表达,主要定位于腺体细胞。
Objectives:To investigate the relationship between expression of adiponectin as well as its receptors in endometrium and high risk of endometrial hyperplasia or even endometrial cancer in patients with polycystic ovary syndrome(PCOS).
Methods:38 PCOS patients served as study group,while 40 cases of normal endometrium as control group.Serum FSH、LH、PRL、T、E_2、CHO、TG、FPG and FINS were determined by enzyme-linked immunosorbent assay(ELISA),and homeostasis model assessment of insulin resistance(HOMA-IR)were calculated.The expression of adiponectin and its two receptors in endometrium were detected by semiquantitive RT-PCR.In addition,immunohistochemical method was used to detect the expression of adiponectin receptorl and 2 in protein level.
Results:(1)Endocrine and metabolic characteristics:FSH 6.81±0.61 IU/L in PCOS group were lower than 8.49±0.92IU/L in control group,P＜0.05;The amount of testorone、LH、CHO、TG、FINS were72.74±7.64ng/dl、9.09±0.89 IU/L、4.99±0.36mmol/L,2.06±0.77mmol/L,9.13±0.59mIU/L in PCOS,which were higher than that in control group with 36.61±6.20 ng/dl、4.55±0.72 IU/L、3.63±0.16mmol/L、1.13±0.15mmol/Land6.52±0.73mIU/L respectively,P＜0.05.(2) Adiponectin and its receptors were all detected in mRNA level in PCOS and control group,and both groups were dominated by AdipoR1,P＜0.05;the expression of AdipoR1 and total Adiponectin receptors were lower in PCOS group(0.91±0.1 and1.22±0.15)than in control women(1.13±0.19and1.45±0.29)with statistical significance (P＜0.05);there were no significant difference in Adiponectin and AdipoR2 expression between two groups.(3)The relationship between serumal FSH level and expression of total Adiponectin receptors was found(r=0.482,p＜0.05),so was FINS and AdipoR1 (r=-0.69,p＜0.05).(4)AdipoR1 and AdipoR2 were detected in protein level in endometrial tissue in both groups.
Conclusion:(1)The expression of total Adiponectin receptors and AdipoR1 in mRNA level in endometrium were declined in PCOS group.So AdipoR1 might play an important role in the conversion of PCOS patients' endometrium from normal to hyperplasia or even cancer.(2)There was a positive correlation between the expression of total Adiponectin receptors in mRNA level and FSH,while negative correlation between AdipoR1 and FINS.(3)Proteins of both AdipoR1 and AdipoR2 were detected in PCOS and normal endometrium,and were mainly located on the membrane of glandular cell.
方法:用酶联免疫吸附法(ELISA)测定PCOS患者38例(PCOS组)和正常妇女40例(正常对照组)血清性激素、促性腺激素、血脂血糖和胰岛素水平;应用逆转录-聚合酶链式反应(RT-PCR)和免疫组化(IHC)的方法检测脂联素及其受体在子宫内膜mRNA表达和蛋白分布;比较PCOS患者与正常对照妇女组脂联素及其受体在子宫内膜表达和分布的差异并寻找其相关影响因素。
结果:(1)血清学检测:PCOS组睾酮72.74±7.64ng/dl明显高于正常对照组36.61±6.20 ng/dl,P＜0.05;PCOS组FSH6.81±0.61 IU/E明显低于正常对照组8.49±0.92IU/L,P＜0.05;PCOS组LH 9.09±0.89 IU/L明显高于正常对照组4.55±0.72IU/L,P＜0.05;PCOS组胆固醇4.99±0.36mmol/L明显高于正常对照组3.63±0.16mmol/L,P＜0.05;PCOS组甘油三脂2.06±0.77mmol/L明显高于正常对照组1.13±0.15mmol/L,P＜0.05;PCOS组空腹胰岛素9.13±0.59mIU/L明显高于正常对照组6.52±0.73mIU/L,P＜0.05;余指标无明显差异。(2)RT-PCR扩增出Adipo,AdipoR1,AdipoR2基因,PCOS组及正常对照组均以AdipoR1为主,AdipoR1与AdipoR2表达量差异有统计学意义(p＜0.05);PCOS组AdipoR1 mRNA 0.91±0.1表达明显低于正常对照组1.13±0.19,差异有统计学意义(P＜0.05);PCOS组总脂联素受体mRNA 1.22±0.15明显低于正常对照组1.45±0.29(P＜0.05);PCOS患者AdipoR2和Adiponectin mRNA表达略低于正常对照组,但差异无统计学意义(P＞0.05)。(3)Spearman相关性分析显示,脂联素总受体mRNA表达量与FSH呈正相关(r=0.482,p＜0.05),AdipoR1mRNA表达与FINS呈负相关(r=-0.69,p＜0.05)。(4)PCOS组和正常对照组子宫内膜免疫组化AdipoR1和AdipoR2呈阳性,主要表达于腺体细胞膜表面。
结论:(1)PCOS患者子宫内膜存在Adiponectin,AdipoR1和AdipoR2在mRNA水平的表达,且以AdipoR1为主。其中AdipoR1和脂联素总受体较正常对照组表达量下降,可能参与了PCOS患者高发子宫内膜增生症甚至癌变的转化过程。(2)脂联素总受体mRNA水平表达量与FSH呈正相关,而AdipoR1与FINS呈负相关。(3)PCOS和正常子宫内膜存在AdipoR1和AdipoR2蛋白水平表达,主要定位于腺体细胞。
Objectives:To investigate the relationship between expression of adiponectin as well as its receptors in endometrium and high risk of endometrial hyperplasia or even endometrial cancer in patients with polycystic ovary syndrome(PCOS).
Methods:38 PCOS patients served as study group,while 40 cases of normal endometrium as control group.Serum FSH、LH、PRL、T、E_2、CHO、TG、FPG and FINS were determined by enzyme-linked immunosorbent assay(ELISA),and homeostasis model assessment of insulin resistance(HOMA-IR)were calculated.The expression of adiponectin and its two receptors in endometrium were detected by semiquantitive RT-PCR.In addition,immunohistochemical method was used to detect the expression of adiponectin receptorl and 2 in protein level.
Results:(1)Endocrine and metabolic characteristics:FSH 6.81±0.61 IU/L in PCOS group were lower than 8.49±0.92IU/L in control group,P＜0.05;The amount of testorone、LH、CHO、TG、FINS were72.74±7.64ng/dl、9.09±0.89 IU/L、4.99±0.36mmol/L,2.06±0.77mmol/L,9.13±0.59mIU/L in PCOS,which were higher than that in control group with 36.61±6.20 ng/dl、4.55±0.72 IU/L、3.63±0.16mmol/L、1.13±0.15mmol/Land6.52±0.73mIU/L respectively,P＜0.05.(2) Adiponectin and its receptors were all detected in mRNA level in PCOS and control group,and both groups were dominated by AdipoR1,P＜0.05;the expression of AdipoR1 and total Adiponectin receptors were lower in PCOS group(0.91±0.1 and1.22±0.15)than in control women(1.13±0.19and1.45±0.29)with statistical significance (P＜0.05);there were no significant difference in Adiponectin and AdipoR2 expression between two groups.(3)The relationship between serumal FSH level and expression of total Adiponectin receptors was found(r=0.482,p＜0.05),so was FINS and AdipoR1 (r=-0.69,p＜0.05).(4)AdipoR1 and AdipoR2 were detected in protein level in endometrial tissue in both groups.
Conclusion:(1)The expression of total Adiponectin receptors and AdipoR1 in mRNA level in endometrium were declined in PCOS group.So AdipoR1 might play an important role in the conversion of PCOS patients' endometrium from normal to hyperplasia or even cancer.(2)There was a positive correlation between the expression of total Adiponectin receptors in mRNA level and FSH,while negative correlation between AdipoR1 and FINS.(3)Proteins of both AdipoR1 and AdipoR2 were detected in PCOS and normal endometrium,and were mainly located on the membrane of glandular cell.
引文
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