不同剂量大豆异黄酮对多囊卵巢综合征大鼠的干预效果研究

Therapeutic Effect of Different Doses of Soy Isoflavoneson PCOS Rats

目的:探讨不同剂量的大豆异黄酮对多囊卵巢综合征(PCOS)大鼠的干预效果。方法:将65只雌性SD大鼠随机分为氯化钠对照组13只,PCOS模型组52只。PCOS模型组造模成功后将PCOS大鼠随机分为模型对照组、二甲双胍组、低剂量(150 mg/kg)大豆异黄酮组和高剂量(250 mg/kg)大豆异黄酮组,每组13只。持续灌胃给药干预21天,期间氯化钠对照组、PCOS模型对照组均以1 ml/100 g 0.9%氯化钠液灌胃。酶联免疫吸附法(ELISA)检测血清激素及IL-1β、IL-18炎症因子水平;qRT-PCR检测卵巢组织中IGF-1和AR基因的表达情况。结果:干预处理后,二甲双胍组、低剂量大豆异黄酮组和高剂量大豆异黄酮组均可恢复大鼠发情周期;3组的体质量、血糖、睾酮(T)、抗苗勒管激素(AMH)、黄体生成素/卵泡刺激素(LH/FSH)、IL-1β和IL-18水平均有显著下降(P<0.05);而雌二醇(E_2)和卵泡刺激素(FSH)水平升高(P<0.05);卵巢组织中IGF-1表达水平下降(P<0.05);两种剂量大豆异黄酮组与二甲双胍组体质量和血糖差异无统计学意义(P>0.05);高剂量大豆异黄酮组血清LH水平显著降低(P<0.05);高剂量组IL-1β和IL-18水平较低剂量组显著降低(P<0.05);低剂量组降调卵巢中AR表达(P<0.05),而高剂量组表现为AR表达水平升高(P<0.05)。结论:大豆异黄酮与二甲双胍干预PCOS可以取得同等的降体质量和血糖的作用,250 mg/kg剂量和150 mg/kg剂量的大豆异黄酮均可改善PCOS大鼠体内激素紊乱状态,改善胰岛素抵抗,恢复正常代谢,250 mg/kg剂量大豆异黄酮有更显著的抗炎作用,但会上调卵巢组织中AR表达,进而有加重高雄激素血症的可能。

Objective:To explore the intervention effects of different doses of soy isoflavones in polycystic ovary syndrome(PCOS)rats.Methods:65 female SD rats were randomly divided into NaCl group(n=13)and model group(n=52).After successful establishment of PCOS model,PCOS rats were randomly divided into model control group,metformin group,low dose(150 mg/kg)soy isoflavone group and high dose(250 mg/kg)soy isoflavone group,with 13 rats in each group.Continuous intragastric administration was intervened for 21 days,during which both the sodium chloride control group and the PCOS model control group were perfused with 1 ml/100 g 0.9%sodium chloride solution.The levels of serum hormones and inflammatory cytokines were valued by Enzyme-linked immunosorbent assay(ELISA).The expression of IGF-1 and AR in rat ovarian tissues were detected by real time PCR.Results:After treated respectively with metformin,low-dose soy isoflavones and high-dose soy isoflavones,it was found that the three interventions could restore the estrous cycle of rats.The weight,blood glucose,testosterone(T),anti-mullerian hormone(AMH),luteinizing hormone/follicle stimulating hormone(LH/FSH),IL-1βand IL-18 levels of the three groups were significantly decreased(P<0.05),while estradiol(E2)and follicle stimulating hormone(FSH)levels were increased(P<0.05).All three interventions could reduce IGF-1 level in ovarian tissue(P<0.05).While there was no significant difference in body mass and blood glucose between the two doses of soy isoflavone group and metformin group(P>0.05).The serum LH level in the high-dose soy isoflavone group was significantly lower than that in the low-dose group(P<0.05),and the levels of IL-1βand IL-18 in the high dose group were significantly lower than those in the low-dose group(P<0.05).The expression of AR in ovary was down-regulated in the low-dose group(P<0.05),while the expression of AR was increased in the high-dose group(P<0.05).Conclusions:Soy isoflavones and metformin intervention in PCOS could achieve the same effect of reducing weight and blood glucose.Both 250 mg/kg and 150 mg/kg soy isoflavones could balance the hormone disorder,reduce insulin resistance,and restore normal metabolism in PCOS rats.250 mg/kg soy isoflavones have a more significant anti-inflammatory effect,while it would up-regulate the expression of AR in ovarian tissue,which may aggravate hyperandrogenemia.