他莫昔芬联合左炔诺孕酮对围绝经期子宫肌瘤大鼠症状改善、子宫内膜厚度的影响及机制分析

Effect of tamoxifen combined with levonorgestrel on symptom improvement and endometrial thickness in perimenopausal uterine myoma rats and its mechanism analysis

目的他莫昔芬联合左炔诺孕酮对围绝经期子宫肌瘤大鼠症状改善、子宫内膜厚度的影响及机制。方法选择清洁级的雌性SD大鼠50只,随机取出10只作为对照组,其余40只分为模型组、他莫昔芬组、左炔诺孕酮组、他莫昔芬联合左炔诺孕酮组,每组10只。对照组与模型组大鼠每天给予2 mL 0.9%氯化钠溶液,他莫昔芬组灌胃给药1.67 mg/kg,左炔诺孕酮组灌胃给药0.1 mg/kg,左炔诺孕酮与他莫昔芬给药剂量及方法同他莫昔芬组与左炔诺孕酮组,5组均连续灌胃30 d。对比5组大鼠的血清性激素、子宫各指标、血管内皮生长因子、低氧诱导因子-1α、血红蛋白、白细胞、血小板、红细胞、血管紧张素Ⅱ、干扰素γ水平,观察5组大鼠的子宫肉眼变化及病理组织学形态。结果与对照组相比,模型组大鼠的血清雌二醇、孕酮、子宫系数、子宫重量、宫体最大直径、左宫角长度、右宫角长度、子宫内膜厚度、血管内皮生长因子、低氧诱导因子-1α、血小板、血管紧张素Ⅱ、干扰素γ水平均升高,血红蛋白、白细胞、红细胞均降低,差异均有统计学意义(P<0.05);与模型组相比,他莫昔芬组、左炔诺孕酮组、他莫昔芬联合左炔诺孕酮组的雌二醇、孕酮、子宫系数、子宫重量、宫体最大直径、左宫角长度、右宫角长度、子宫内膜厚度、血管内皮生长因子、低氧诱导因子-1α、血小板、血管紧张素Ⅱ、干扰素γ水平均降低,血红蛋白、白细胞、红细胞均升高,差异均有统计学意义(P<0.05);与左炔诺孕酮组、他莫昔芬组相比,他莫昔芬联合左炔诺孕酮组以上指标变化更显著,差异均有统计学意义(P<0.05)。结论与单独应用他莫昔芬、左炔诺孕酮相比,他莫昔芬联合左炔诺孕酮可显著改善围绝经期子宫肌瘤大鼠的症状,降低子宫内膜厚度,可能与其可降低血管内皮生长因子、低氧诱导因子-1α、血管紧张素Ⅱ、干扰素γ水平有关。

Objective To investigate the effect of tamoxifen combined with levonorgestrel on symptom improvement and endometrial thickness in perimenopausal uterine myoma rats and its mechanism analysis.Methods Fifty female SD rats of clean grade were selected and 10 were randomly selected as control group,the remaining 40 rats were divided into model group,tamoxifen group,levonorgestrel group,tamoxifen combined with levonorgestrel group,with 10 rats in each group.Rats in control group and model group were given 2 mL 0.9%normal saline every day,while rats in tamoxifen group were given 1.67 mg/kg by gavage.The levonorgestrel group was given 0.1 mg/kg by gavage,and the dosage and method of levonorgestrel and tamoxifen were the same as those of tamoxifen group and levonorgestrel group.All the 5 groups were given gavage for 30 days.The levels of serum sex hormone,uterine indicators,vascular endothelial growth factor,hypoxia-inducible factor-1α,hemoglobin,white blood cells,platelets,red blood cells,angiotensinⅡ,interferonγwere compared between the five groups.The macroscopic changes and histopathological morphology of the uterus were observed.Results Compared with the control group,the serum estradiol,progesterone,uterine coefficient,uterine weight,maximum uterine body diameter,left uterine horn length,right uterine horn length,endometrial thickness,vascular endothelial growth factor,hypoxia-inducible factor-1α,platelet,angiotensinⅡ,interferonγof rats in the model group were all increased,the levels of hemoglobin,white blood cells and red blood cells were decreased,and the differences were statistically significant(P<0.05).Compared with the model group,the levels of estradiol,progesterone,uterine coefficient,uterine weight,maximum diameter of uterine body,length of left uterine horn,length of right uterine horn,thickness of endometrium,vascular endothelial growth factor,hypoxia-inducible factor-1α,platelets,angiotensinⅡand interferonγin tamoxifen group,levonorgestrel group and tamoxifen combined with levonorgestrel group were decreased,and hemoglobin,white blood cells and red blood cells increased,the differences were statistically significant(P<0.05).Compared with levonorgestrel group and tamoxifen group,tamoxifen combined with levonorgestrel group had more significant changes in the above indicators(P<0.05).Conclusion Compared with tamoxifen and levonorgestrel alone,tamoxifen combined with levonorgestrel can significantly improve the symptoms and reduce endometrial thickness in perimenopausal rats with uterine fibroids,which may be related to the reduction of vascular endothelial growth factor,hypoxia-inducible factor-1α,angiotensin II,interferonγ.