荔枝核水提液对胰岛素抵抗协同性激素诱导的子宫肌瘤大鼠模型的影响-现代医学

荔枝核水提液对胰岛素抵抗协同性激素诱导的子宫肌瘤大鼠模型的影响

单位：1. 广州中医药大学第一附属医院药学部, 广东广州 510405;
2. 广州中医药大学第一附属医院妇儿中心, 广东广州 510405;
3. 广州中医药大学第一临床医学院, 广东广州 510405

分类号：R737.33

出版年·卷·期（页码）：2022·50·第二期（151-156）

摘要：

目的:基于糖代谢指标、血清性激素及其受体探讨荔枝核水提液对胰岛素抵抗协同性激素诱导的子宫肌瘤大鼠模型的影响。方法:48只雌性大鼠分为空白对照组,模型对照组,阳性对照组,荔枝核高、中、低剂量组,除空白对照组外其余5组大鼠采用胰岛素抵抗协同性激素刺激的方法建立大鼠子宫肌瘤模型,造模成功后阳性对照组二甲双胍(150 mg·kg^-1)灌胃,1次·d^-1,荔枝核高、中、低剂量组荔枝核水提液(高剂量组44 g·kg^-1,中剂量组22 g·kg^-1,低剂量组11 g·kg^-1)灌胃,1次·d^-1。各组大鼠采用苏木精-伊红(HE)染色法观察子宫病理切片,采用血糖仪检测空腹血糖(FPG),采用酶联免疫吸附测定法(ELISA)测定血清空腹胰岛素(FINS)、雌二醇(E₂)水平以及子宫匀浆血管内皮生长因子(VEGF)浓度,采用免疫组化法检测子宫组织雌激素受体(ER)、孕激素受体(PR)表达情况。结果:模型对照组大鼠子宫平滑肌呈不同程度的增生,平滑肌细胞排列紊乱,肌纤维排列疏松;而空白对照组及各干预组平滑肌肌层较薄,平滑肌细胞细长,排列整齐。与空白对照组比较,模型对照组FPG、FINS浓度以及胰岛素抵抗指数(IRI)均显著升高(P<0.05);与模型对照组比较,阳性对照组,荔枝核低、中、高剂量组的FPG和FINS均显著下降(P<0.05),阳性对照组、荔枝核中剂量和高剂量组的IRI值均显著下降(P<0.05)。与空白对照组比较,模型对照组血清E₂和子宫匀浆VEGF浓度显著升高(P<0.05);与模型对照组比较,阳性对照组、荔枝核中剂量和高剂量组的血清E₂均显著下降(P<0.05),阳性对照组及荔枝核低、中、高剂量组的子宫匀浆VEGF浓度均显著下降(P<0.05)。与空白对照组比较,模型对照组子宫组织中ER和PR的平均光密度值(AOD值)显著升高(P<0.05);与模型对照组比较,阳性对照组及荔枝核低、中、高剂量组ER的AOD值均显著下降(P<0.05),而阳性对照组、荔枝核高剂量组PR的AOD值显著下降(P<0.05)。结论:荔枝核水提液可明显改善子宫肌瘤模型大鼠的子宫组织病理形态学改变,改善胰岛素抵抗,降低大鼠异常升高的血清E₂和子宫VEGF含量,降低子宫组织ER和PR的表达,从而抑制子宫肌瘤的生长,且其治疗作用具有浓度依赖性。

Objective:To investigate the effects of litchi seed water extract on insulin resistance and sex hormone induced uterine fibroids in rats based on glucose metabolism,serum sex hormones and their receptors.Methods:48 female rats were divided into blank control group,model control group,positive control group,litchi seed high-dose group,medium-dose group and low-dose group.Except the blank control group,the other five groups were given insulin resistance combined with sex hormone stimulation to establish rat uterine leiomyoma model.The positive control group was given metformin (150 mg·kg^-1) once a day,and litchi seed high-dose group,medium-dose group and low-dose group were given litchi seed water extract once a day (44 g·kg^-1 for high dose,22 g·kg^-1 for medium dose and 11 g·kg^-1 for low dose).The pathological sections of uterus were observed by hematoxylin-eosin (HE) staining,fasting plasma glucose (FPG) was detected by blood glucose meter,the serum levels of fasting insulin (FINS) and estradiol (E₂) and vascular endothelial growth factor (VEGF) concentration in uterus homogenate were detected by enzyme linked immunosorbent assay (ELISA),and the expression ofestrogen receptor (ER) and progesterone receptor (PR) in uterus tissue was detected by immunohistochemistry.Results:In the model control group,uterine smooth muscle cells were proliferated in varying degrees,smooth muscle cells arranged disorderly and muscle fibers arranged loosely;while in the blank control group and the intervention groups,the smooth muscle layer was thin,smooth muscle cells were slender and arranged orderly.Compared with the blank control group,FPG,FINS and insulin resistance index (IRI) of the model control group were significantly increased (P<0.05);compared with the model control group,FPG and FINS of the positive control group,low-dose group,medium-dose group and high-dose group were significantly decreased (P<0.05),and IRI of the positive control group,medium-dose group and high-dose group were significantly decreased (P<0.05).Compared with the blank control group,the concentration of serum E₂ and VEGF in uterine homogenate of the model control group were significantly increased (P<0.05);compared with the model control group,the concentration of serum E₂ in the positive control group,medium-dose group and high-dose group were significantly decreased (P<0.05),and the concentration of VEGF in uterine homogenate of the positive control group,low-dose group,medium-dose group and high dose group were significantly decreased (P<0.05).Compared with the blank control group,the average optical density (AOD) values of ER and PR in the model control group were significantly increased (P<0.05);compared with the model control group,the AOD values of ER in the positive control group,low-dose group,medium-dose group and high-dose group were significantly decreased (P<0.05),while the AOD values of PR in the positive control group and high-dose group were significantly decreased (P<0.05).Conclusion:Litchi seed water extract can significantly improve the pathomorphological changes of uterine tissue,improve insulin resistance,reduce the abnormally elevated serum E₂ and uterine VEGF content,and reduce the expression of ER and PR in uterine tissue,so as to inhibit the growth of uterine fibroids,and its therapeutic effect is concentration dependent.

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