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目的:对乳康口服液治疗乳腺增生的作用机制做进一步研究。方法:实验分为6组:正常对照组、模型对照组、三苯氧胺组和乳康口服液低、中、高剂量组,用苯甲酸雌二醇注射液和黄体酮注射液制备大鼠乳腺增生模型后再予相应药物治疗。给药结束后应用ELISA法测定雌激素受体(ER)、孕激素受体(PR)、P53、Oct4的浓度,用Western blot检测乳腺组织ER、PR、P53和Oct4表达,用荧光定量PCR法检测促性腺激素释放激素(GnRH)及其受体(GnRHR)的表达,原位杂交法检测乳腺组织端粒酶的表达。结果:乳康口服液可以降低血清和乳腺组织中ER、PR的表达量(P<0.01),降低P53、端粒酶及Oct4的表达(P<0.01),降低下丘脑GnRH及垂体GnRH受体表达(P<0.01),从多方面逆转乳腺增生,发挥其治疗作用。结论:乳康口服液可通过抑制降低血清和乳腺组织中ER、PR的表达,下丘脑GnRH及垂体GnRH受体表达等途径发挥药效学。同时乳康口服液可能会通过降低与乳腺癌发生相关的三个相关标志物P53、端粒酶和Oct4表达量来发挥预防乳腺增生发展为乳腺癌的功效。
Objective: To further study the mechanism of action of Rukang Oral Liquid in the treatment of mammary gland hyperplasia. Methods: The experiment was divided into 6 groups: normal control group, model control group, tamoxifen group and Rukang oral low, medium and high dose groups, with estradiol benzoate injection and progesterone injection of rat mammary gland hyperplasia model Then give the appropriate drug treatment. The concentrations of estrogen receptor (ER), progesterone receptor (PR), P53 and Oct4 were measured by ELISA after the administration. The expression of ER, PR, P53 and Oct4 in breast tissues were detected by Western blot. The expression of gonadotropin-releasing hormone (GnRH) and its receptor (GnRHR) was detected and the expression of telomerase in breast tissue was detected by in situ hybridization. Results: Rukang oral liquid can reduce the expression of ER and PR (P <0.01), reduce the expression of P53, telomerase and Oct4 (P <0.01), and decrease the expression of GnRH and pituitary GnRH receptor in hypothalamus (P <0.01), reversing the hyperplasia of mammary glands from many aspects and exerting its therapeutic effect. CONCLUSION: Rukang oral liquid can exert pharmacodynamics by inhibiting the expression of ER, PR, GnRH in hypothalamus and GnRH receptor in pituitary gland. Meanwhile, Rukang oral liquid may play an important role in preventing breast hyperplasia and developing breast cancer by reducing P53, telomerase and Oct4 expression related to breast cancer.