金雀异黄素对多囊卵巢综合征大鼠性激素水平的影响

Effect of genistein on the level of sex hormones in rats with polycystic ovary syndrome

目的研究金雀异黄素(GEN)对多囊卵巢综合征(PCOS)大鼠性激素水平及卵巢组织3β-羟基甾脱氢酶(3β-HSD)、细胞色素P450芳香化酶(P450arom)的影响。方法将120只大鼠随机分为对照组(n=30)、模型组(n=30)及低剂量实验组(n=30)、高剂量实验组(n=30)。模型组及低、高剂量实验组大鼠均灌胃来曲唑1 mg·kg^(-1)·d^(-1),连续21 d,建立PCOS模型。造模成功后,低、高剂量实验组大鼠灌胃金雀异黄素10,20 mg·kg^(-1)·d^(-1),对照组与模型组灌胃等量生理盐水,连续14 d。用酶联免疫吸附(ELISA)法检测血清黄体生成素(LH)、促卵泡生成素(FSH)、睾酮(T)、雌二醇(E2)水平;用蛋白质印迹(Wb)法与免疫组化法检测大鼠卵巢组织3β-HSD和P450arom蛋白表达。结果对照组、模型组与低、高剂量实验组大鼠血清LH水平分别为(21.57±4.48),(50.37±5.65),(39.11±6.02),(30.21±5.84)mU·mL^(-1);FSH水平分别为(7.42±3.36),(16.51±4.24),(12.64±5.38),(9.84±2.56)mU·mL^(-1);T水平分别为(0.68±0.17),(1.93±0.74),(1.39±0.51),(1.02±0.33)ng·mL^(-1);E2水平分别为(25.32±3.43),(9.96±3.85),(14.46±2.52),(19.33±2.91)pg·mL^(-1)。模型组大鼠血清LH、FSH、T水平及3β-HSD蛋白相对表达量、阳性细胞百分比均较对照组升高,且低、高剂量实验组较模型组显著降低;E2水平及P450arom蛋白相对表达量、阳性细胞百分比均较对照组降低,且低、高剂量实验组较模型组升高,并呈剂量依赖性(均P<0.05)。结论金雀异黄素可调节PCOS大鼠血清性激素水平,发挥雌激素作用,改善卵巢功能,其机制可能与下调卵巢组织3β-HSD蛋白表达,上调P450arom蛋白表达有关。

Objective To investigate the effects of genistein(GEN)on sex hormone levels and 3β-hydroxypurine dehydrogenase(3β-HSD)and cytochrome P450 aromatase(P450 arom)in ovarian tissues of rats with polycystic ovary syndrome(PCOS).Methods A total of 120 SD rats were randomly divided into control group(n=30),model group(n=30)and Exp-L/H groups(n=30).Rats in model group and Exp-L/H groups were given letrozole 1 mg·kg^(-1)·d^(-1)by gavage for 21 d to establish PCOS model.After successful modeling,rats in Exp-L/H groups were given GEN 10,20 mg·kg^(-1)·d^(-1)by gavage,the same volume of normal saline were given to control group and model group for 14 d.Serum luteinizing hormone(LH),follicle stimulating hormone(FSH),testosterone(T),and estradiol(E2)levels were measured by enzyme-linked immunosorbent assay;Western blotting and immunohistochemistry method were used to detect the expression of 3β-HSD and P450 arom protein in rat ovarian tissues.Results Serum LH levels in control group,model group and Exp-L/H groups were(21.57±4.48),(50.37±5.65),(39.11±6.02),(30.21±5.84)m U·mL^(-1),respectively;the FSH levels were(7.42±3.36),(16.51±4.24),(12.64±5.38)and(9.84±2.56)m U·mL^(-1),the T levels were(0.68±0.17),(1.93±0.74),(1.39±0.51),(1.02±0.33)ng·mL^(-1);the E2 levels were(25.32±3.43),(9.96±3.85),(14.46±2.52)and(19.33±2.91)pg·mL^(-1).Compared with control group,serum LH,FSH,T levels and relative expression and percentage of 3β-HSD protein positive cells were significantly increased in model group,and Exp-L/H groups were significantly lower than model group;the E2 level and relative expression and percentage of P450 arom protein positive cells were significantly decreased,Exp-L/H groups were significantly higher than model group,with dose-dependent(all P<0.05).Conclusion GEN can regulate serum sex hormone levels in PCOS rats,play an estrogen role,and improve ovarian function,and its mechanism may be related to down-regulating the expression of 3β-HSD protein and up-regulating the expression of P450 arom protein.