内异康复片调控GPER-Ras-STAT3通路治疗子宫腺肌病的机制

Mechanism of Neiyi Kangfu Tablets in treatment of adenomyosis through regulating GPER-Ras-STAT3 signal pathway

目的探究内异康复片(鳖甲、牡蛎、大黄,等)对子宫腺肌病的治疗作用及其可能作用机制。方法通过异体垂体移植手术建立小鼠子宫腺肌病模型,采用不同剂量的内异康复片、丹莪妇康煎膏(丹参、莪术、赤芍,等)和孕三烯酮分别给药治疗,灌胃治疗3个月后取样,应用Western blot、real-time PCR、免疫组化SP法检测在位和异位内膜上的GPER-Ras-STAT3通路的表达。结果高剂量的内异康复片可以显著下调GPER蛋白(G蛋白偶联雌激素受体蛋白)和基因的表达,下调Ras和STAT3(信号转导和转录激活因子3)的蛋白表达,降低异位病灶严重程度的组织形态学评分,且其疗效优于丹莪妇康煎膏和孕三烯酮。结论内异康复片可能通过抑制GPER-Ras-STAT3通路活性,弱化雌激素的生成,从而控制异位病灶的发展。

AIM To study the therapeutic effects of Neiyi Kangfu Tablets （Trionycis Carapax, Ostreae concha, Rhei Radix et Rhizoma, etc. ） on adenomyosis and its possible mechanism of action. METHODS The mouse model for adenomyosis was set up by the pituitary allograft, and received the gavage of Neiyi Kangfu Tablets, Dan＇e Fukang Decoction （Salviae mihiorrhizae Radix et Rhizoma, Curcumae Rhizoma, Paeoniae Radix rubra, etc. ） and gestrinone, respectively, for three months. Western blot, real-time PCR, IHC were used to measure the expression of GPER-Ras-STAT3 in ectopic endometrium and entopic endometrium. RESULTS High doses of Neiyi Kangfu STAT3 protein Tablets could significantly lower GPER protein and gene expression; downregulate the Ras and expression; reduce the lesion severity score of ectopic tissue morphology. Its curative effect was better than Dan＇ e Fukang Decoction and gestrinone. CONCLUSION Neiyi Kangfu Tablets may control the devel-opment of ectopic lesions by inhibiting the GPER-Ras-STA33 pathway activity and weakening the production of es-trogen.