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

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

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。

Objective： To investigate the effects of aromatase and cyclooxygenase-2 inhibitors on rat models of endometriosis in vivo. Methads： 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）, ovariectomized 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 remarldy 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 imageanalysis 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）. Conelutions： Effect ofaromatase 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.