目的 探讨槲皮素对先兆流产大鼠的保胎作用和对激素水平的影响。方法 50只妊娠大鼠随机分为正常组、模型组、槲皮素组、AG490组和槲皮素+AG490组,各10只,槲皮素组、AG490组和槲皮素+AG490组分别给予2.5 mg/ml槲皮素、0.5 mg/kg AG490和2.5 mg/ml槲皮素+0.5 mg/kg AG490灌胃干预,1次/d,连续7 d,正常组、模型组灌胃等量生理盐水,妊娠8 d除正常组外其余各组大鼠以米非司酮和米索前列醇建立先兆流产模型,妊娠9 d各组大鼠按原剂量继续灌胃4 d;妊娠14 d处死大鼠,检测血清激素及免疫因子水平,计算流产率、胚胎吸收率和脏器系数,HE染色观察子宫组织形态学变化。结果 与模型组比较,槲皮素组血清雌二醇、β-人绒毛膜促性腺激素(β-HCG)、孕激素、白细胞介素-10(IL-10)水平和子宫组织磷酸化Janus激酶2(p-JAK2)、磷酸化信号传导及转录激活因子3(p-STAT3)蛋白相对表达量升高,血清干扰素-γ(IFN-γ)、肿瘤坏死因子-α(TNF-α)水平降低,卵巢、子宫合重增加,脏器系数升高,流产率、胚胎吸收率降低(P＜0.05),AG490组血清雌二醇、β-HCG、孕激素、IL-10水平和子宫组织p-JAK2、p-STAT3蛋白相对表达量降低,血清IFN-γ、TNF-α水平升高,卵巢、子宫合重减小,脏器系数降低(P＜0.05);与槲皮素组比较,槲皮素+AG490组血清雌二醇、β-HCG、孕激素、IL-10水平和子宫组织p-JAK2、p-STAT3蛋白相对表达量降低,血清IFN-γ、TNF-α水平升高,卵巢、子宫合重减小,脏器系数降低,胚胎吸收率升高(P＜0.05);与AG490组比较,槲皮素+AG490组血清雌二醇、β-HCG、孕激素、IL-10水平和子宫组织p-JAK2、p-STAT3蛋白相对表达量升高,血清IFN-γ、TNF-α水平降低,卵巢、子宫合重增加,脏器系数升高,胚胎吸收率降低(P＜0.05)。结论 槲皮素对先兆流产大鼠具有保胎作用,可提高其激素水平,机制可能与调控JAK2/STAT3通路有关。

Objective To investigate the effect and mechanism of quercetin on anti-abortion and hormone levels in threatened abortion in rats. Methods Fifty pregnant rats were randomly divided into the normal group,model group,quercetin group,AG490 group and quercetin+AG490 group,with 10 rats in each.The last three groups were given intragastrically 2.5 mg/ml quercetin,0.5 mg/kg AG490 and 2.5 mg/ml quercetin+0.5 mg/kg AG490 respectively once a day for seven consecutive days while the first two groups were given intragastrically an equal amount of normal saline.Eight days after pregnancy, all the rats except the normal group were given mifepristone and misoprostol to establish a model of threatened abortion.Nine days after pregnancy, rats in each group were given intragastrically the original dose for four days.The rats were sacrificed on the 14th day of pregnancy,and the levels of serum hormones and immune factors were detected.The abortion rate,embryo absorption rate and organ coefficient were calculated.HE staining was used to observe the morphological changes of uteri. Results Compared with the model group,the levels of serum estradiol,β-human chorionic gonadotropin, progesterone and IL-10 and the relative expressions of phosphorylated Janus kinase2 and phosphorylated signal transducers and activators of transcription3 in uterine tissues were increased in the quercetin group, the levels of serum interferon-γ and tumor necrosis factor-α were decreased, the weight of ovaries and uteri was increased, the organ coefficient was increased, while the abortion rate and embryo absorption rate were decreased (P＜0.05). In the AG490 group, the levels of serum estradiol,β-HCG,progesterone and IL-10, and the relative expressions of p-JAK2 and p-STAT3 in uterine tissues were decreased, the levels of serum IFN-γ and TNF-α were increased, the weight of ovaries and uteri was decreased, and the organ coefficient was decreased (P＜0.05). Compared with the quercetin group, the levels of serum estradiol,β-HCG,progesterone and IL-10. and the relative expressions of p-JAK2 and p-STAT3 protein in uterine tissues decreased, the levels of serum IFN-γand TNF-α increased, the weight of ovaries and uteri decreased, the organ coefficient decreased, and the embryo absorption rate increased in the quercetin+AG490 group (P＜0.05).Compared with the AG490 group, the levels of serum estradiol, β-HCG, progesterone and IL-10, and the relative expressions of p-JAK2 and p-STAT3 protein in uterine tissues in the quercetin+AG490 group were increased, the levels of serum IFN-γ and TNF-α were decreased, the weight of ovaries and uteri was increased, the organ coefficient was increased, and the embryo absorption rate was decreased(P＜0.05). HE staining showed that the endometrium of the model group became thinner, most of the nodules were not dilated, and the glands were atrophic, like the uteri of unpregnant rats. In the quercetin group, endometrial thickening, nodular enlargement, increased numbers of glands, and ameliorated gland atrophy were observed. Compared with the model group, the endometrium of the AG490 group was thinner without nodular enlargement, and the number of glands was reduced accompanied by severe atrophy. The endometrium of the quercetin+AG490 group was thicker than that of the AG490 group, with nodular enlargement, increased numbers of glands and reduced atrophy. Conclusions Quercetin has an anti-abortional effect on threatened abortion in rats by increasing their hormone levels. he mechanism may be related to the regulation of JAK2/STAT3 pathway.