Xia Xiaomeng, Guo Lilu, Su Jinping, Fang Xiaoling
Department of Gynecology and Obstetrics, Second Xiangya Hospital, Central South University, Changsha 410011, China.
Zhong Nan Da Xue Xue Bao Yi Xue Ban. 2013 Jan;38(1):54-9. doi: 10.3969/j.issn.1672-7347.2013.01.010.
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.
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.
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).
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.
探讨第三代芳香化酶抑制剂来曲唑对大鼠子宫内膜异位症模型异位病灶的治疗机制及其对异位子宫内膜细胞凋亡的影响。
通过将大鼠子宫组织自体移植到腹膜上诱导子宫内膜异位症。异位移植成功的大鼠分为2组:来曲唑组(n = 15)和对照组(n = 15)。在治疗前后测定异位移植灶的体积、外观和组织病理学。通过免疫组织化学和RT-PCR检测两组异位移植灶中P450arom、COX-2、bcl-2和bax的表达。
与对照组相比,来曲唑组异位移植灶的体积显著减小(P < 0.05)。与对照组相比,来曲唑组异位移植灶中P450arom和COX-2的蛋白和mRNA水平显著降低(P < 0.05)。P450arom的表达与COX-2的表达呈正相关(r = 0.943,P < 0.001;r = 0.913,P < 0.001)。与对照组相比,来曲唑组异位移植灶中bcl-2的蛋白和mRNA表达显著降低(P < 0.05),bax蛋白和mRNA表达显著增加(P < 0.05),bax/bcl-2比值升高(P < 0.05)。
来曲唑可通过降低P450arom和COX-2表达、抑制雌激素分泌、抑制增殖并诱导异位病灶凋亡,明显减小异位移植灶的大小。