来曲唑对大鼠子宫内膜异位症的作用及对异位内膜细胞凋亡的影响

目的:初步探讨第3 代芳香化酶抑制剂来曲唑治疗大鼠子宫内膜异位症(endometriosis, EM) 模型异位病灶的作用机制, 及对异位内膜细胞凋亡的影响。方法:用自体子宫内膜移植方法建立大鼠EM 模型, 选择建模成功的大鼠随机分为来曲唑组(n=15) 和对照组(n=15), 比较治疗前后两组大鼠异位病灶的体积、外观变化、病理组织学差异, 并采用免疫组织化学法和RT-PCR 法检测异位病灶中P450 芳香化酶(P450arom)、环氧合酶-2(COX-2)、bcl-2及bax 的表达。结果:与对照组比较, 来曲唑组异位病灶体积明显缩小(P<0.05), 异位病灶中P450arom 和COX-2的蛋白及mRNA 表达均明显减低(P<0.05)。P450arom 与COX-2 在异位病灶中的表达呈正相关(r=0.943, P<0.001;r=0.913, P<0.001)。异位病灶中bcl-2 的蛋白及mRNA 表达较对照组均明显减低(P<0.05), bax 的蛋白及mRNA 表达较对照组明显增高(P<0.05), 来曲唑组bax/bcl-2 的比值较对照组显著增加(P<0.05)。结论:来曲唑可明显缩小异位病灶体积, 可能通过降低异位病灶局部P450arom, COX-2 的表达, 抑制雌激素生成及异位病灶的增殖, 从而促进异位病灶细胞凋亡, 达到治疗目的。

Effect of letrozole on endometrosis and apoptosis of ectopic endometrial cells in rats

Objective: To investigate the therapeutic mechanism of letrozole, the third-generation aromatase inhibitor, on endometriotic lesions in a rat model and its effect on the apoptosis of ectopic endometrial cells.
Methods: Endometriosis was induced by autotransplanting pieces of uterus onto the peritoneum in rats. The rats with successful ectopic implants were divided into 2 groups: A letrozole group (n=15) and a control group (n=15). The volume, appearance, and histopathology of ectopic implant were determined before and after the treatment. Expression of P450arom, COX-2, bcl-2, and bax in the ectopic implant was detected by immunohistochemistry and RT-PCR in the 2 groups. Results: The volume of ectopic implant in the letrozole group was significantly reduced compared with the control group (P<0.05). The protein and mRNA levels of P450arom and COX-2 in the ectopic implant were significantly decreased in the letrozole group compared with the control group (P<0.05). There was a positive correlation between the expression of P450arom and the expression of COX-2 (r=0.943, P<0.001; r=0.913, P<0.001). The protein and mRNA expression of bcl-2 was significantly decreased (P<0.05), and the bax protein and mRNA expression was significantly increased (P<0.05) in the ectopic implant with an increased bax/bcl-2 ratio in the letrozole group compared with the control group (P<0.05).
Conclusion: Letrozole can obviously reduce the size of ectopic implant through decreasing P450arom and COX-2 expression, suppressing the secretion of estrogen, inhibiting the proliferation, and inducing the apoptosis of ectopic implants.