金雀异黄素对实验性雌性大鼠高雄激素血症的治疗作用

THE THERAPEUTIC EFFECT OF GENISTEIN ON EXPERIMENTAL HYPERANDROGENISM IN FEMALE RATS

目的探讨金雀异黄素(genistein,Gen)对多囊卵巢综合征(polycystic ovary syndrome,PCOS)高雄激素血症大鼠血清性激素各项检测指标及卵巢组织中促卵泡生成素受体(follicle-stimulating hormone receptor,FSHR)蛋白和促黄体生成素受体(luteinizing hormone receptor,LHR)蛋白的作用。方法按照胰岛素(INS)联合人体绒毛膜促性腺激素(HCG)造模法建立PCOS实验动物模型,分为阴性对照组(control group,CG)、模型组(model group,MG)、Gen低、中、高(L-Gen,M-Gen,H-Gen)及雌激素阳性对照组(estrogen group,EG),剂量组分别灌胃给予Gen 5、10、20 mg/(kg.bw.d),雌激素组给予己烯雌酚0.5mg/kg,持续15d,观察动情周期10d。采用酶联免疫法(ELISA)测定大鼠血清中促黄体生成素(luteinizing hormone,LH)、促卵泡生成素(follicle-stimulating hormone,FSH)、睾酮(testosterone,T)、孕酮(progesterone,P)及性激素结合球蛋白(sex hormone binding globulin,SHBG)水平,计算LH/FSH比值;免疫组化法测定卵巢组织中FSHR蛋白和LHR蛋白水平。结果与模型组相比,M-Gen、H-Gen组及雌激素组大鼠血清P水平升高,差异极显著(P<0.01)。L-Gen组大鼠血清T水平下降,差异显著(P<0.05);M-Gen,H-Gen组和雌激素组T水平下降,差异极显著(P<0.01)。与模型组相比,各剂量组大鼠血清SHBG水平均增高,差异极显著(P<0.01)。各剂量组大鼠血清中LH水平均下降,差异极显著(P<0.01);各剂量组FSH水平增高,其中H-Gen组和雌激素组增高明显,差异极显著(P<0.01);各剂量组LH/FSH比值呈下降趋势,其中M-Gen,H-Gen组和雌激素组下降明显,差异极显著(P<0.01)。免疫组化结果显示与模型组相比,给予Gen[10,20 mg/(kg bw.d)]后,大鼠卵巢颗粒细胞中FSHR蛋白表达减弱,平均阳性面积和平均光密度下降;LHR蛋白表达增强,平均阳性面积和平均光密度均增加,差异显著(P<0.01)。结论血清中LH高水平、T增高及高雄激素血症可能是引起PCOS发生的因素之一。Gen可有效调节PCOS高雄血症大鼠血清性激素水平,对大鼠卵巢组织中FSHR蛋白及LHR蛋白均有调节作用,提示其对PCOS可起到治疗作用。

Objective To study the therapeutic effect of genistein （GEN） on serum sex hormone and luteinizing hormone receptor （FSHR） protein, luteinizing hormone receptor （LHR） protein of ovary in female rats with polycystic ovary syndrome （PCOS） and hyperandrogenism. Method The insulin （INS） combined with human chorionic gonadotropin （HCG） molding method was used to establish PCOS animal model. Sixty rats were divided into control group, model group, low, middle, high dose Gen groups （L-G, M-G, H-G） given Gen 5, 10, 20 mg/kg bw respectively and estrogen group （EG）, given diethylstilbestrol 0.5 mg/kg bw, All compounds were administered i.g on 15 consecutive days and the estrous cycle was observed for l0 d. The levels of progesterone （P）, testosterone （T）, sex hormone binding globulin （SHBG）, follicle- stimulating hormone （FSH） and luteinizing hormone （LH） in serum and FSHR protein, LHR protein of ovary were examined. Results Comoared with the model ~roun_ the level afP increased significantly in M-G 14-G and EC~ prnlln~ （P〈（~ 01＂~ Th（~level of T decreased significantly in M-G, H-G and EG （P 〈 0.01）. The level of LH decreased significantly in all dose groups （P〈0.01）. The level of FSH increased significantly in H-G and EG （P〈0.01）. The ratio of LH/FSH decreased significantly in M-G, H-G and EG （P〈 0.01）. Immunohistochemical results showed that compared with the model group, the expression of FSHR protein in rats＇ ovarian granulosa cells decreased after giving Gen （10,20 mg/kg bwod）. The average positive area and average density decreased. LHR protein expression increased. The average positive area and average density increased （P〈0.01）. Conclusion High level of LH in serum increased T concentration and hyperandrogenism may be the reasons for PCOS. Concentration of sex hormones in serum was regulated efficiently by Gen. Gen also has effect on FSHR protein and LHR protein in rats＇ ovarian tissue. It is presumed that the plant estrogenic effects of Gen may have therapeutic effect on PCOS oatients.