桂枝茯苓胶囊联合戈舍瑞林对子宫肌瘤大鼠模型醛酮还原酶1C3和内分泌的影响

Effects of Guizhi Fuling Capsules Combined with goserelin on Aldo-keto reductase family 1 member C3 and endocrine in a rat model of uterine leiomyomas

目的观察桂枝茯苓胶囊联合戈舍瑞林对子宫肌瘤大鼠模型醛酮还原酶1C3(AKR1C3)和内分泌的影响。方法将36只7周龄雌性白细胞介素-2受体共同Υ链(IL2RG)大鼠随机分为空白对照组、模型对照组和联合治疗组,每组各12只。模型对照组和联合治疗组通过雌孕激素药物建立子宫肌瘤模型。造模结束后第2天,空白对照组和模型对照组予蒸馏水5 mL灌胃,联合治疗组予桂枝茯苓胶囊混悬液0.70 g/(kg·d)+戈舍瑞林1.25 mg/(kg·d)灌胃,连续6周。采用酶联免疫吸附法测定各组大鼠血清雌二醇、孕酮和催乳素水平,实时荧光定量聚合酶链式反应法检测AKR1C3 mRNA表达,蛋白免疫印迹法检测Ⅰ型胶原、转化生长因子β(TGF-β)、纤溶酶原激活物抑制剂-1(PAI-1)、半胱氨酸天冬氨酸蛋白酶-3(Caspase-3)、B淋巴细胞瘤-2(Bcl-2)、Bcl-2相关X蛋白(Bax)蛋白表达。结果与空白对照组相比,模型对照组雌二醇、孕酮和催乳素含量均升高(P<0.05);与模型对照组相比,联合治疗组雌二醇、孕酮和催乳素含量降低(P<0.05)。与空白对照组相比,模型对照组AKR1C3 mRNA表达含量升高(P<0.05);与模型对照组相比,联合治疗组AKR1C3 mRNA表达含量降低(P<0.05)。与空白对照组相比,模型对照组Ⅰ型胶原、PAI-1和TGF-β蛋白表达均升高(P<0.05);与模型对照组相比,联合治疗组Ⅰ型胶原、PAI-1和TGF-β蛋白表达均降低(P<0.05)。与空白对照组相比,模型对照组Caspase-3和Bax蛋白表达降低(P<0.05),Bcl-2蛋白表达升高(P<0.05);与模型对照组相比,联合治疗组Caspase-3和Bax蛋白表达升高(P<0.05),Bcl-2蛋白表达降低(P<0.05)。结论桂枝茯苓胶囊联合戈舍瑞林能降低子宫肌瘤大鼠雌二醇、孕酮和催乳素水平,抑制AKR1C3表达,具有抗增殖和促凋亡的作用,可抑制子宫肌瘤生长。

Objective To explore the effects of Guizhi Fuling Capsules combined with goserelin on Aldo-keto reductase family 1 member C3(AKR1C3)and endocrine in a rat model of uterine leiomyomas.Methods Thirty-six 7-week-old female interleukin-2 receptor gamma chain gene(IL2RG)-deficient rats were randomly divided into blank control group,model group and combination group,with 12 rats per group.Rats in the latter two groups were modeling for uterine leiomyomas by medications of estrogen and progesterone drugs.On the second day after the modeling,rats in the blank control group and model group were given oral gavage of 5 mL of distilled water,those in the combination group were given oral gavage of Guizhi Fuling Capsule suspension(0.70 g/kg/d)+goserelin(1.25 mg/kg/d)for consecutive 6 weeks.Enzyme-linked immunosorbent assay(ELISA)was used to measure serum estradiol,progesterone and prolactin levels.Quantitative real-time polymerase chain reaction(QRT-PCR)was performed to detect the mRNA level of AKR1C3.Western blotting was used to detect protein expressions of collagen typeⅠ(Col-Ⅰ),transforming growth factor β(TGF-β),plasminogen activator inhibitor-1(PAI-1),caspase-3,B-cell lymphoma 2(Bcl-2)and Bcl-2-related X protein(Bax).Results The levels of serum estradiol,progesterone and prolactin in the model group were significantly higher compared with the blank control group(P<0.05),and which in the combination group were significantly lower compared to the model group(P<0.05).The mRNA level of AKR1C3 was significantly higher in the model group relative to the blank control group(P<0.05),and which was significantly lower in the combination group than that of the model group(P<0.05).The protein levels of Col-I,TGF-β and PAI-1 were significantly higher in the model group versus the blank control group(P<0.05),and which were significantly lower in the combination group versus the model group(P<0.05).Compared with blank control group,the protein level of Caspase-3 and Bax in the model group was significantly lower,and that of Bcl-2 was significantly higher(P<0.05).Compared with the model group,the protein levels of Caspase-3 and Bax in the combination group were significantly higher,and the protein level of Bcl-2 was significantly lower(P<0.05).Conclusion Guizhi Fuling Capsules combined with goserelin can reduce serum estradiol,progesterone and prolactin,inhibit the expression of AKR1C3,suppress the proliferation and stimulate the apoptosis in rats,showing the inhibitory effect on the growth of uterine leiomyomas.