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郑娟, 谈勇. 定坤丹联合戊酸雌二醇对肾阳虚薄型子宫内膜大鼠Wnt/β-catenin信号通路的影响[J]. 四川大学学报(医学版), 2021, 52(2): 235-240. DOI: 10.12182/20210160508
引用本文: 郑娟, 谈勇. 定坤丹联合戊酸雌二醇对肾阳虚薄型子宫内膜大鼠Wnt/β-catenin信号通路的影响[J]. 四川大学学报(医学版), 2021, 52(2): 235-240. DOI: 10.12182/20210160508
ZHENG Juan, TAN Yong. Influence of Dingkun Dan Combined with Estradiol Valerateon Wnt/β-catenin Signaling Pathway in Rats with Thin Endometrium with Kidney-Yang Deficiency[J]. Journal of Sichuan University (Medical Sciences), 2021, 52(2): 235-240. DOI: 10.12182/20210160508
Citation: ZHENG Juan, TAN Yong. Influence of Dingkun Dan Combined with Estradiol Valerateon Wnt/β-catenin Signaling Pathway in Rats with Thin Endometrium with Kidney-Yang Deficiency[J]. Journal of Sichuan University (Medical Sciences), 2021, 52(2): 235-240. DOI: 10.12182/20210160508

定坤丹联合戊酸雌二醇对肾阳虚薄型子宫内膜大鼠Wnt/β-catenin信号通路的影响

Influence of Dingkun Dan Combined with Estradiol Valerateon Wnt/β-catenin Signaling Pathway in Rats with Thin Endometrium with Kidney-Yang Deficiency

  • 摘要:
      目的  探讨定坤丹联合戊酸雌二醇对肾阳虚薄型子宫内膜大鼠Wnt/β-连环蛋白(β-catenin)信号通路的影响。
      方法  选取处于动情期的雌性SD大鼠40只,随机分为空白组、模型组、定坤丹组、戊酸雌二醇组、联合用药组,每组8只。除空白组外,其余各组大鼠建立肾阳虚薄型子宫内膜模型。空白组自由饮食,模型组给予蒸馏水灌胃,定坤丹组灌服定坤丹2.26 g/(kg·d),戊酸雌二醇组灌服戊酸雌二醇0.3 mg/(kg·d),联合用药组在戊酸雌二醇0.3 mg/(kg·d)基础上同时给予定坤丹2.26 g/(kg·d)。经过3个动情周期后,处死大鼠,取材。HE染色观察大鼠子宫内膜组织形态学变化。免疫组织化学染色检测血管内皮生长因子(VEGF)的表达,Western blot法检测大鼠子宫内膜中β-catenin、E钙粘蛋白(E-cadherin)、基质金属蛋白酶-9(MMP-9)蛋白的表达。
      结果  与空白组比较,模型组大鼠子宫腔狭窄或增大,内膜层腺体、血管稀疏,子宫内膜变薄(P<0.01),VEGF表达降低(P<0.01),β-catenin、E-cadherin、MMP-9蛋白表达升高(P<0.01)。与模型组比较,各治疗组内膜腺体较多,分布均匀,内膜层血管丰富,内膜增厚(P<0.01或P<0.05),VEGF表达呈不同程度升高,β-catenin、E-cadherin蛋白表达水平降低(P<0.01),定坤丹组与联合用药组MMP-9蛋白表达水平降低(P<0.01)。与戊酸雌二醇组比较,定坤丹组β-catenin蛋白水平更高(P<0.05),MMP-9蛋白水平更低(P<0.01);联合用药组β-catenin、MMP-9蛋白表达水平均降低(P<0.01)。与联合用药组比较,定坤丹组β-catenin蛋白水平更高,E-cadherin蛋白水平更低(P<0.01或P<0.05)。
      结论  定坤丹联合戊酸雌二醇通过上调肾阳虚薄型子宫内膜大鼠子宫内膜VEGF表达,下调β-catenin、E-cadherin和MMP-9蛋白水平,增厚大鼠子宫内膜。

     

    Abstract:
      Objective  To explore the influence for combination of Dingkun Dan with estradiol valerateon in treating rats with thin endometrium with Kidney-Yang deficiency based on Wnt/β-catenin signaling pathway.
      Methods  The estrous period 40 rats were randomly divided into the normal control group, the model group, the Dingkun Dan group, the estradiol valerateon group and the combination group, with 8 rats in each group. In addition to the normal control group, the rat model of thin endometrium with Kidney-Yang deficiency was established in other groups. The control group used free diet, the model group was given distilled water, the estradiol valerateon group was treated with progynova by gavage at 0.3 mg/(kg·d) , Dingkun Dan group was treated with Dingkun Dan by gavage at 2.26 g/(kg·d), and the combined group was given Dingkun Dan at 2.26 g/(kg·d) on the basis of progynova at 0.3 mg/(kg·d). After 3 estrous cycles, the rats were killed and harvested. HE staining was used to observe histopathologic changes in endometrium. The expression of VEGF in rats endometrium were detected by immunohistochemistry. The expression of β-catenin, E-cadherin and MMP-9 protein in rat endometrium was detected by Western blot.
      Results  Compared with the control group, the uterine cavity was narrowed or enlarged, the endometrium glands and blood vessels were sparse, and the endometrium was thinner significantly in the model group (P<0.01); the levels of VEGF was decreased significantly (P<0.01), while β-catenin, E-cadherin and MMP-9 were increased significantly (P<0.01). Compared with the model group, more endometrial glands, rich intimal vessels, the endometrium were thickened significantly in the 3 treatment groups (P<0.01 or P<0.05); the levels of VEGF was increased differently. The protein levels of β-catenin and E-cadherin were significantly decreased in each treatment group (P<0.01), and MMP-9 were significantly decreased in the Dingkun Dan group and in the combination group (P<0.01). Compared with the estradiol valerateon group, the level of β-catenin in Dingkun Dan group was higher, and MMP-9 was lower (P<0.05 or P<0.01). The levels of β-catenin and MMP-9 in the combination group were significantly decreased (P<0.01). Compared with the combination group, the levels of β-catenin was increased significantly, while decreased signicantly in Dingkun Dan group (P<0.01 or P<0.05).
      Conclusion  Dingkun Dan combined with estradiol valerateon can increase the thicken of the endometrium by up-regulation of VEGF, while down-regulate of β-catenin, E-cadherin and MMP-9 in rats with Shen-Yang deficiency and thin endometrium.

     

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