芳香化酶及环氧合酶抑制剂对大鼠子宫内膜异位症模型的作用

目的:探讨芳香化酶抑制剂(Arimidex)、环氧合酶-2抑制剂(celecoxib)对大鼠子宫内膜异位症(内异症)模型的作用。方法:采用子宫内膜自体移植方法建立大鼠内异症模型,将40只内异症大鼠随机分为5组(n=8):A:Arimidex组;B:celecoxib组:C:联合组;D:双卵巢切除组(OVX组);E:盐水对照组(NS对照组)。RIA方法测定各组血清FSH、LH、E2水平;检测各组处理前后异位囊肿体积变化;计算机图像分析各组异位内膜病理形态。结果:Arimidex单用或与celecoxib联合治疗1周均降低大鼠内异症模型血清E2水平(P<0.05),治疗4周对血清E2水平均无明显影响(P>0.05),治疗1周、4周血清FSH、LH水平略升高但与对照组比较差异均无统计学意义(P>0.05);单用celecoxib对大鼠内异症模型血清E2、FSH、LH水平无影响(P>0.05)。Arimidex组、联合治疗组及去势组均可使异位囊肿体积明显缩小(P<0.01);囊肿消失率:联合治疗组(37.5%)及去势组(50%)均较高,有统计学意义(P<0.05),Arimidex组、celecoxib组则无统计学意义。Arimidex组、联合治疗组及去势组均可使子宫内膜及腔上皮明显变薄(P<0.01), celecoxib组不影响异位子宫内膜厚度及腔上皮高度(P>0.05);Arimidex组、celecoxib组、联合治疗组未明显改变腺上皮高度及腺腔外径(P>0.05)。结论:芳香化酶抑制剂联合环氧合酶-2抑制剂对大鼠内异症异位内膜的作用略优于单用芳香化酶抑制剂;两者治疗1周可使血清E2水平降低, FSH、LH略升高;治疗4周对血清E2、FSH、LH无明显影响;环氧合酶抑制剂单用效果不明显。

Effects of Aromatase and Cyclooxygenase-2 Inhibitors on Endometriosis in Rat Models

Objective: To investigate the effects of aromatase and cyclooxygenase-2 inhibitors on rat models of endometriosis in vivo. Methods: Surgically transplanted au-tologous uterine tissues to ectopic sites beside the uterines in rats were used as animal models to study endometriosis. 40 rats were then divided into five groups (n=8): Arimidex-treated group (A), Celecoxib-treated group (B), combination-treated group (C), ovariecto-mized group (D), saline solution-oralled group as control (E). Radioimmunoassay was used to detect the serum levels of E2, FSH and LH in each group after 1 week and 4 weeks therapy; Macroscopic changes of endometriotic explants were observed and histologic and image analysis were also done. Results: The serum levels of E2 decreased remarkly when rat models were treated with Arimidex alone or combined with celecoxib after 1 week (P<0.05), and they were restored to the same levels as the control's when the models had been administrated for 4 weeks (P>0.05).The serum levels of FSH and LH increased slightly when rats exposed to the conditions mentioned above after 1 week or 4 weeks but were no statistically significant difference as compared with that of the controls (P>0.05). Celecoxib alone showed little effect on the serum levels of E2, FSH and LH (P>0.05). The explant sizes in group A, C and D significantly dwindled (P<0.01), and they showed no changes in celecoxib-treated group. The percentage of explant disappearance was shown as follow: 37.5% in group C (P<0.05), 50% in group D (P<0.01), 12.5% in group A (P>0.05), 6.25% in group B and control group respectively. Histologic and image-analysis results showed that the thickness of ectopic endometrium and endometrial cavity epithelia cells in group A, C and D significantly reduced as compared with that in the control (P<0.01), while they showed no effect in group B. There were no changes about the thickness of endometrial glands epithelia cells and the cavity diameter of glands in group A, C and D (P>0.05). Conclutions: Effect of aromatase inhibitor in combination with cyclooxygenase-2 inhibitor on endometriotic explants of rat models proved obvious, and it was slightly superior to that of aromatase inhibitor alone. Aromatase inhibitor alone or in combination with cyclooxygenase-2 inhibitor could decrease the serum level of E2 in rat models and slightly increase the serum levels of FSH and LH after 1 week tharepy. However, both showed no effect on the serum levels of E2, FSH and LH after 4 weeks tharepy. Celecoxib alone showed no significant effect on rat endometriosis.