Caspase-8、NF-kB在经Gen处理后的大鼠子宫内膜异位症中的表达

Expressions of Caspase-8 and NF-kB in endometriosis of rats treated with genistein

目的:观察Caspase-8,NF-kB在经金雀异黄素(Genistein,Gen)处理后的大鼠子宫内膜异位症中的表达,初步探讨金雀异黄素对大鼠子宫内膜异位症治疗的作用机制。方法:采用外科手术法建立大鼠EMs模型,将大鼠随机分为Ⅰ组15只(对照组)、Ⅱ组15只(Gen低剂量治疗组,0.5 mg·kg-1·d-1)、Ⅲ组15只(Gen高剂量治疗组,50 mg·kg-1·d-1)。连续皮下注射药物12周,再次检测移植物体积变化,运用HE染色观察移植内膜组织的病理改变,免疫组化法检测大鼠异位内膜组织中Caspase-8及NF-kB的表达。结果:移植物外观:与对照组比较,Gen高剂量治疗组移植物体积明显缩小(P<0.01)。病理学变化:与对照组比较,Gen治疗组移植腺体可见部分萎缩、变矮、消失,其上皮细胞层厚度变薄,可见部分腺上皮脱落,结构不清;其中以Gen高剂量组效果最明显,与对照组比较,Caspase-8在Gen治疗组中的表达率明显升高(P<0.05);Caspase-8在Gen高剂量组中的阳性表达率为80.0%,明显高于Gen低剂量组的69.2%,差异有统计学意义(P<0.01)。与对照组比较,治疗组中NF-kB表达率无明显差异(P>0.05)。结论:在经Gen处理后的大鼠EMs中,Gen诱导Caspase-8调节细胞凋亡,表明Caspase-8通过调节细胞凋亡参与了Gen治疗子宫内膜异位症的发生、发展过程。Gen对大鼠EMs具有良好的抑制其组织增生、促进细胞凋亡的作用,其作用机制可能是通过NF-kB以外的传导途径对EMs发挥作用。

Objective： To observe the expressions of caspase - 8 and NF - kB in endometriosis of rats treated with genistein, preliminarily explore the mechanism of genistein in treatment of endometriosis in rats. Methods： Rat model of endometriosis was established by surgical operation method, then the rats were randomly divided into group I （control group, 15 rats）, group II （low- dose genistein group, 0. 5 mg · kg-1 · d-1 , 15 rats）, group 111 （high -dose genistein group, 50 mg · kg-1 · d-1 , 15 rats） . All rats were treated with subcutaneous injection of drug for 12 weeks, and the change of graft volume was measured again. HE staining was usedlo observe the pathological changes of transplanted endometrial tissue ; immunohistochemical method was used to detect the expressions of Caspase - 8 and NF - kB in endometriosis. Results： Morphology of graft ： compared with control group, graft volume in high - dose genistein group decreased significantly （P 〈 0. 01 ） . Pathological change： compared with control group, atrophy, shortening, and disappearance of partial glands were found in genistein groups, the thickness of epithelial cell layer became thinner, partial glandular epithelial cells shed, the structure was un- clear, especially in high - dose genistein group, compared with control group, the expression rate of Caspase - 8 in genistein groups increased significantly （ P 〈 0.05 ） ; the positive expression rate of Caspase - 8 in high - dose genistein group was 80.0%, which was statisti- cally significantly higher than that in low - dose genistein group （P 〈 0. 01 ） ; there was no statistically significant difference in the positive expression rate of NF - kB between control group and genistein groups （P 〉 0. 05） . Conclusion ： Genistein can induce apoptosis regulated by Caspase - 8 in rates with endometriosis treated with genistein, which indicates that Caspase - 8 participates in occurrence and development of endometriosis by regulating apoptosis; genistein can inhibit proliferation of endometrial cells and promote apoptosis, which may play a part by conduction pathways except NF -kB.