定坤丹治疗子宫内膜异位症的药理作用与机制

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目的:通过大鼠子宫内膜自体移植模型研究定坤丹治疗痛经及子宫内膜异位症(endometriosis,EMS)的疗效和相关机制。方法:将成功建模组大鼠随机分成5组,每组7只,模型对照组(B组)、孕三烯酮阳性对照组(C组)和定坤丹低剂量组(D组,相当于临床人用剂量)、中剂量组(E组,相当于临床人用剂量2倍)、高剂量(F组,相当于临床人用剂量4倍),并以5只假手术大鼠为正常对照组(A组),检测用药后血清雌、孕激素水平、异位内膜包囊数及异位内膜血管内皮生长因子/血管内皮生长因子受体(VEGF/VEGFR2)表达水平的变化。结果:定坤丹对大鼠血清雌、孕激素水平没有显著影响,但能显著抑制异位内膜包囊的生长,抑制率F组为63.9%±20.0%,E组为54.1%±22.1%,D组为51.9%±23.7%,与B组比,均有统计学差异(P=0.000);与C组(47.0%±45.0%)比无统计学差异(P>0.05)。异位内膜VEGF/VEGFR2表达水平的免疫组织化学和免疫印迹分析结果显示,定坤丹治疗导致异位内膜分泌VEGF减少,异位内膜包囊壁基质中的VEGFR2下调,包囊壁上皮VEGFR2高水平表达。结论:定坤丹治疗能显著抑制异位内膜包囊的生长,VEGF/VEGFR2改变可能与异位内膜包囊壁上皮层的脱落和包囊腔的形成有关。 OBJECTIVE: To study the curative effect and mechanism of Dingkundan on dysmenorrhea and endometriosis (EMS) through rat endometrial autotransplantation model. Methods: The rats in the model group were randomly divided into 5 groups (7 rats in each group). The model control group (group B), the gestagene-positive control group (group C) and the Dingkudan low-dose group In the clinical human dose), the middle dose group (E group, equivalent to 2 times the clinical human dose), high dose (F group, equivalent to 4 times the clinical human dose), and 5 sham rats were normal Control group (group A). ​​The changes of serum estrogen and progesterone levels, ectopic endometrial cysts and ectopic endometrial vascular endothelial growth factor / vascular endothelial growth factor receptor (VEGF / VEGFR2) levels were detected after treatment. Results: Dingkunantan had no significant effect on serum estradiol and progesterone levels, but significantly inhibited the growth of ectopic endometrial cysts. The inhibition rate was 63.9% ± 20.0% in F group and 54.1% ± 22.1% in E group , And 51.9% ± 23.7% in group D, which were significantly different from those in group B (P = 0.000). There was no significant difference between group C and group C (47.0% ± 45.0%) (P> 0.05). Immunohistochemical and immunoblot analysis of VEGF / VEGFR2 expression levels in ectopic endometrium showed that treatment with Dingkudan resulted in decreased VEGF secretion in ectopic endometrium, decreased VEGFR2 in ectopic endometrial capsule wall, VEGFR2 is expressed at high levels. Conclusion: Dingkunantan treatment can significantly inhibit the growth of ectopic endometrial capsule, and the changes of VEGF / VEGFR2 may be related to the exfoliation of the ectopic endometrial capsule wall and the formation of the cyst cavity.
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