Gong Jin, Wu Dong-bo, Zhang Lan-lan, Li Jia, Zhao Xing, Zhang Dan
Sichuan Da Xue Xue Bao Yi Xue Ban. 2015 Mar;46(2):238-42, 247.
To establish a pathological animal model of polycystic ovary (PCO) by letrozole in rats. Investigate whether PCO were mediated by the effect of oxidative stress by measuring oxidative stress levels in this cohort of rats with PCO, and proceed a new way of treatment for polycystic ovary syndrom (PCOS).
90 SD female rats aged 6 weeks were randomly divided into two groups, including a control group of 45 rats that received vehicle only [19% aqueous solution of carboxmethlycellulose (CMC), 1 mL/d] once daily orally (p.o.), and an experimental group of 45 rats, which were administered letrozole at concentrations of 1 mg/kg p.o. dissolved in 1% CMC (1 mL/d) once daily. The treatment period was 28 d. During this period, vaginal smears were collected daily for estrus cycle determination and body masses were measured every 7 d. On the day subsequent to the last letrozole dose administration, rats were killed; Uteri and ovaries were then excised and weighed for the calculation of organ indexes. Serum hormone levels, SHBG and histologic changes in the ovaries were examined. Then testosterone free index (FAD) was calculated. Oxidant status was evaluated by determination of ovarian total oxidant status (TOS), malondialdehyde (MDA) concentration and intracellular reactive oxygen species (ROS) level, while antioxidant status was evaluated by determination of total antioxidant status (TAS) and superoxide dismutase (SOD) concentration.
Vaginal smear test showed the estrus cycle began to disappear from day 12 to day 15. A statistically significant difference in growth curves, ovarian weights, uterine weights and organ indexes between the groups were also observed. In rats with PCO serum testosterone (T), follicle-stimulating hormone (FSH) concentrations and free androgen index (FADI) were significantly increased compared with the control group (rats without PCO). However, rats with PCO had decreased levels of estrogen (E2), luteinizing hormone (LH), and progesterone (P) compared with the control group. In a rat model of PCO achieved via letrozole, it was found that the levels of TOS, MDA, oxidative stress index (OSI) and intracellular ROS were significantly increased, while the TAS level, SOD content were significantly decreased in the ovary homogenates (P<0.05). The results indicated that the PCOS pathological process significantly increased the oxidative stress production.
PCO rat model successfully induced via letrozole, and it is a suitable model for study of ovarian lesions. Oxidative stress also contributes to the PCO rat model, the protective effect of antioxidant might provide a new insight into the potential therapeutic solution to PCOS.
通过来曲唑建立大鼠多囊卵巢(PCO)病理动物模型。通过测量该组PCO大鼠的氧化应激水平,研究PCO是否由氧化应激作用介导,并探索多囊卵巢综合征(PCOS)的新治疗方法。
将90只6周龄的SD雌性大鼠随机分为两组,其中对照组45只大鼠,每日经口(p.o.)给予仅含赋形剂[19%羧甲基纤维素(CMC)水溶液,1 mL/d];实验组45只大鼠,每日经口给予溶解于1% CMC(1 mL/d)中的1 mg/kg来曲唑。治疗期为28天。在此期间,每天采集阴道涂片以确定发情周期,每7天测量体重。在末次给予来曲唑后的次日,处死大鼠;然后切除子宫和卵巢并称重以计算器官指数。检测血清激素水平、性激素结合球蛋白(SHBG)及卵巢组织学变化。然后计算游离睾酮指数(FAD)。通过测定卵巢总氧化状态(TOS)、丙二醛(MDA)浓度和细胞内活性氧(ROS)水平评估氧化状态,同时通过测定总抗氧化状态(TAS)和超氧化物歧化酶(SOD)浓度评估抗氧化状态。
阴道涂片试验显示发情周期从第12天至第15天开始消失。两组之间在生长曲线、卵巢重量、子宫重量和器官指数方面也观察到统计学上的显著差异。与对照组(无PCO的大鼠)相比,PCO大鼠血清睾酮(T)、促卵泡激素(FSH)浓度和游离雄激素指数(FADI)显著升高。然而,与对照组相比,PCO大鼠的雌激素(E2)、促黄体生成素(LH)和孕酮(P)水平降低。在通过来曲唑建立的PCO大鼠模型中,发现卵巢匀浆中TOS、MDA、氧化应激指数(OSI)和细胞内ROS水平显著升高,而TAS水平、SOD含量显著降低(P<0.05)。结果表明PCOS病理过程显著增加了氧化应激产生。
通过来曲唑成功诱导了PCO大鼠模型,它是研究卵巢病变的合适模型。氧化应激也促成了PCO大鼠模型,抗氧化剂的保护作用可能为PCOS的潜在治疗方案提供新的见解。