内异康复片对子宫腺肌病小鼠P450arom-COX-2-PGE2正反馈环的调控机制的研究

Research on regulatory mechanism of Neiyikangfu Pills on P450arom-COX-2-PGE2 positive feedback loop of mice with adenomyosis

目的:通过观察P450arom、环氧化酶2(COX-2)、前列腺素E2(PGE2)在子宫腺肌病(AM)治疗前后随动情周期变化的表达差异,及其各组在位及异位内膜上的表达差异,研究内异康复片治疗AM的作用靶点,以探索内异康复片治疗AM的作用机制。方法:采用异体垂体移植的手术方法造模,采用免疫组化方法,观察各组在动情期和间情期及治疗前后在位及异位内膜雌激素效应相关因子的表达。结果:P450、PGE2、COX-2的表达,在6月模型组和3月模型组显著高于正常组(P<0.01),且6月模型组高于3月模型组(P<0.05)。3个指标的表达在不同治疗组治疗后有所下降(P<0.05,P<0.01),且内异康复片高剂量组优于其它各治疗组。动情期指标表达高于间情期(P<0.05)。结论:内异康复片能够通过下调在位及异位内膜雌激素效应相关因子P450、COX-2、PGE2表达,阻断雌激素生成的正反馈环,抑制雌激素对异位病灶的影响效应,从而控制和治疗AM,缓解临床症状。

Objective: To study the action target of Neiyikangfu Pills in the treatment of adenomyosis(AM), by observing the expression difference of P450 arom, COX-2, PGE2 along with changes of estrous cycle before and after the treatment of AM, so as to explore the action mechanism of Neiyikangfu Pills in the treatment of AM. Methods: Animal model was established by allosome pituitary transplantation method, and immunohistochemical method was used to observe the relative factors expression of estrogen effect of eutopic endometrium and endometriosis in estrum, diestrus, before and after the treatment. Results: The values of P450, PGE2, and COX-2 in 6 months group and 3 months group were significantly higher than those in normal group and Sham-operated group(P<0.01). And the values in 6 months group were higher than those in 3 months group(P<0.05). The values of three index were all declined in different treatment groups after treatment(P<0.05, P<0.01), and the values of high dose group of Neiyikangfu Pills were better than other treatment groups. The values in estrum were higher than those in diestrus(P<0.05). Conclusion: Neiyikangfu Pills can block the positive feedback loop generated by lowering the values of the relative factors expression of estrogen effect of eutopic endometrium and endometriosis including P450, COX-2, PGE2, and restrain the influential effect of estrogen on ectopic foci, so as to control and treat AM and relive clinical symptoms.