子宫内膜异位症模型大鼠NF-KB及炎性因子、粘附因子变化及对细胞侵袭和凋亡的影响

Changes of NF KB,inflammatory factors,and metabolic factors of model rats with endometriosis and their influences on cell invasion and apoptosis

目的:探究子宫内膜异位症模型大鼠核转录因子KappaB(NF-κB)和炎性因子、粘附因子的表达变化及其对内膜细胞侵袭和凋亡的影响。方法:将SD大鼠随机分为对照组、模型组、阳性组和PDTC组,除对照组外,其余组大鼠采用自体移植法建立子宫内膜异位症大鼠模型。建模成功后,阳性组大鼠腹腔注射0.25mg/kg/d的孕三烯酮,PDTC组大鼠腹腔注射100mg/kg/d的脯氨酸二硫代氨基甲酸酯(PDTC)溶液,对照组和模型组大鼠腹腔注射等体积的生理盐水,连续注射21d。western blot检测内膜细胞的NF-κB活性,酶联免疫吸附法检测肿瘤坏死因子-α(TNF-α)、白细胞介素-6(IL-6)、白细胞介素-1β(IL-1β)、细胞粘附分子(ICAM-1)和血管粘附分子(VCAM-1)水平,Transwell小室分析内膜细胞的侵袭水平, TUNEL染色检测内膜细胞凋亡情况。结果:大鼠子宫内膜细胞NF-κB活性,模型组高于对照组,阳性组和PDTC组低于模型组(均P<0.05);大鼠内膜细胞TNF-α、IL-6、IL-1β、ICAM-1、VCAM-1的水平,模型组高于对照组,阳性组和PDTC组低于模型组(均P<0.05)。Transwell结果显示,大鼠的细胞侵袭能力模型组较对照组显著增加,阳性组和PDTC组较模型组明显下降(均P<0.05);TUNEL染色显示,大鼠的细胞凋亡指数模型组较对照组显著下降,阳性组和PDTC组较模型组明显下降(均P<0.05)。结论:子宫内膜异位模型大鼠NF-κB的活性明显增加,可能是通过靶向上调炎性因子和粘附因子的表达,促进内膜细胞的侵袭,并抑制其凋亡。

Objective:To investigate the changes of NF-κB,inflammatory factors,and metabolic factors of model rats with endometriosis,and to study their influences on cell invasion and apoptosis.Methods:SD rats were randomly divided into group A(control group),group B(model group),group C(positive group),and group D(PDTC group).The model rats with endometriosis in group A,B,and C were built by autotransplantation.The model rats in group C were injected intraperitoneally with 0.25 mg/kg/d of gestrinone for 21 days,the model rats in group D were injected intraperitoneally with a PDTC solution of 100 mg/kg/d for 21 days,and the model rats in group A and B were injected intraperitoneally with equal doses of normal saline for 21 days.The NF-κB activity was detected by western blot,the TNF-α,IL-6,IL-1β,ICAM 1,and VCAM 1 were analyzed by ELISA,the Transwell was used to analyze the invasion of intimal cells,and the TUNEL staining was used to detect the intimal cell apoptosis.Results:The activity of NF-κB and the levels of TNF-α,IL-6,IL-1β,ICAM-1,and VCAM-1 of the endometrial cells of rats in group B were significant higher than those of rats in group A,and those of rats in group C and D were significant lower than those of rats in group B(P<0.05).Transwell showed that the cell invasion of rats in group B was significant higher than that of rats in group A(P<0.05),while that of rats in group C and D was significant lower than that of rats in group B(all P<0.05).TUNEL staining showed that the apoptosis index of rats in group B was significant lower than that of rats in group A(P<0.05),and which of rats in group C and D was significant lower than that of rats in group B(all P<0.05).Conclusion:The activity of NF-κB of model rats with endometriosis increases significantly,which maybe promote the invasion of endometrial cells and inhibite their apoptosis by up regulating the expression of inflammatory and adhesion factors.