萝卜硫素对子宫内膜异位症模型大鼠在位内膜增殖、血管生成及JAK2/STAT3信号通路的影响

Effect of sulforaphane on eutopic endometrial proliferation,angiogenesis and JAK2/STAT3 signaling pathway in rat model of endometriosis

目的:探讨萝卜硫素对子宫内膜异位症(EMT)模型大鼠在位内膜增殖、血管生成及JAK2/STAT3信号通路的(SFN)5 mg/kg组、SFN 10 mg/kg组和SFN 15 mg/kg组。C组只开腹不移植;其余组大鼠采用自体子宫内膜组织移植法建立子宫内膜异位症模型。测量异位病灶重量和体积,以及在位内膜厚度。采用免疫组化法测定在位内膜组织中增殖细胞核抗原(PCNA)表达和微血管密度(MVD)。Western blot测定在位内膜组织中细胞周期蛋白D1(cyclin D1)、血管内皮生长因子(VEGF)、JAK2、磷酸化JAK2(p-JAK2)、STAT3、p-STAT3蛋白水平。结果:不同浓度SFN组大鼠异位病灶重量和体积均较小于模型组(P<0.05),且SFN对大鼠异位病灶重量和体积的影响呈剂量依赖性。取10 mg/kg SFN用于后续研究。M组大鼠在位内中PCNA蛋白灰度值低于C组(P<0.05),SFN 10 mg/kg组大鼠在位内膜组织中PCNA蛋白灰度值高于M组(P<0.05)。M组大鼠在位内膜组织中cyclin D1、VEGF、p-JAK2、p-STAT3蛋白水平高于C组(P<0.05),SFN 10 mg/kg组大鼠在位内膜组织中cyclin D1、VEGF、p-JAK2、p-STAT3蛋白水平低于M组(P<0.05)。结论:萝卜硫素可抑制EMT大鼠在位内膜增殖、抑制血管生成和JAK2/STAT3信号通路激活。

Objective:To investigate the effects of sulforaphane on eutopic endometrial proliferation,angiogenesis and JAK2/STAT3 signaling pathway of eutopic endometrium(EMT)model rats in order to elucidate the possible action mechanism of sulforaphane on eutopic endometrium.Methods:Rats were divided into control group(C group),model group(M group),sulforaphane(SFN)5 mg/kg group,SFN 10 mg/kg group and SFN 15 mg/kg group. In C group,only laparotomy was performed without transplantation.Endometriosis models were established by autologous endometrial tissue transplantation in the remaining groups of rats. The weight and volume of the ectopic lesions were measured,and the intimal endometrial thickness was measured. Immunohistochemistry method was used to determine the expression of proliferating cell nuclear antigen(PCNA)and microvessel density(MVD)in eutopic endometrial tissue. Levels of cyclin D1,vascular endothelial growth factor(VEGF),JAK2,phosphorylated JAK2(p-JAK2),STAT3 and p-STAT3 protein in eutopic endometrial tissue were determined by Western blot.Results:The weight and volume of ectopic lesions in rats with different concentrations of SFN groups were smaller than those in the model group(P<0.05),and the effects of SFN on the weight and volume of ectopic lesions in rats were dose-dependent. 10 mg/kg SFN was used for subsequent research.The eutopic endometrial thickness and MVD of rats in M group were greater than those in C group(P<0.05).The eutopic endometrial thickness and MVD value of SFN 10 mg/kg group rats were smaller than those of M group(P<0.05). The gray value of PCNA protein in eutopic endometrium of M group rats was lower than that of C group(P<0.05). The gray value of PCNA protein in eutopic endometrial tissue of rats in SFN 10 mg/kg group was higher than that in M group(P<0.05). The cyclin D1,VEGF,p-JAK2 and p-STAT3 protein levels in the eutopic endometrium of M group rats were higher than those of C group(P<0.05).The cyclin D1,VEGF,p-JAK2 and p-STAT3 protein levels in the eutopic endometrial tissue of the SFN 10 mg/kg group were lower than those of the M group(P<0.05).Conclusion:Sulforaphane can inhibit eutopic endometrial proliferation,inhibit angiogenesis and inhibit JAK2/SAT3 signaling pathway activation in EMT rats.