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目的:探讨第3代芳香化酶抑制剂(aromatase inhibitors,AIs)来曲唑治疗大鼠子宫内膜异位症模型的效果及作用机制。方法:用自体子宫内膜移植方法建立大鼠内异症模型,随机将20只建模成功大鼠分为来曲唑组和盐水对照组,比较治疗前后EM大鼠异位病灶体积的变化;免疫组化法检测异位内膜病灶中细胞色素P450芳香化酶(P450arom)、环氧合酶-2(COX-2)、血管内皮生长因子(VEGF)、增殖细胞核抗原(PCNA)蛋白的表达;末端转移酶介导的缺口末端标记法(TUNEL)检测细胞凋亡情况;放射免疫分析法测定大鼠血清FSH、LH、E2水平。结果:来曲唑组异位病灶体积缩小(P<0.01);异位内膜中P450arom、COX-2、VEGF、PCNA蛋白表达与对照组相比均明显降低(P<0.05);来曲唑组异位内膜细胞凋亡率较对照组明显增加(P<0.01);两组大鼠血清FSH、LH、E2水平无明显差异(P>0.05)。结论:来曲唑治疗大鼠子宫内膜异位症模型有效。来曲唑通过降低异位内膜局部P450arom、COX-2、VEGF蛋白表达及抑制异位内膜增殖并促进凋亡发挥治疗子宫内膜异位症的作用。来曲唑对大鼠血清FSH、LH、E2水平无明显影响。
Objective: To investigate the effect and mechanism of third generation aromatase inhibitors (AIs) letrozole in rat endometriosis model. Methods: Endometriosis model was established by autologous endometrial transplantation. Twenty healthy rats were randomly divided into letrozole group and saline control group. The volume of ectopic lesion in EM rats was compared before and after treatment. The expression of cytochrome P450 aromatase (P450arom), cyclooxygenase-2 (COX-2), vascular endothelial growth factor (VEGF) and proliferating cell nuclear antigen (PCNA) in ectopic endometrial lesions were detected by immunohistochemistry ; The apoptosis was detected by TUNEL; The level of serum FSH, LH, E2 was determined by radioimmunoassay. Results: The volume of ectopic lesion in letrozole group was decreased (P <0.01). The expression of P450arom, COX-2, VEGF and PCNA in ectopic endometrium was significantly lower than that in control group (P <0.05) The apoptosis rate of ectopic endometrial cells was significantly higher than that of the control group (P <0.01). There was no significant difference in serum FSH, LH and E2 between the two groups (P> 0.05). Conclusion: Letrozole is effective in treating endometriosis in rats. Letrozole plays a role in the treatment of endometriosis by decreasing the expression of P450arom, COX-2 and VEGF in ectopic endometrium and inhibiting the proliferation of ectopic endometrium and promoting apoptosis. Letrozole had no significant effect on serum FSH, LH and E2 levels in rats.