大蒜素调控PI3K/Akt/Nrf2通路对大鼠子宫内膜异位症的影响  

Effect of Allicin Modulation of PI3K/Akt/Nrf2 Pathway on Endometriosis in Rats

作　　者：董秀娟[1] 曹若愚 于洪基 窦素棉 DONG Xiujuan;CAO Ruoyu;YU Hongji(Cangzhou Central Hospital, Hebei Cangzhou 061000, China)

机构地区：[1]河北省沧州市中心医院产科,河北沧州061000

出　　处：《河北医学》2022年第4期572-577,共6页Hebei Medicine

基　　金：河北省医学科学研究课题,(编号:20201541)。

摘　　要：目的:研究大蒜素对大鼠子宫内膜异位症(EMs)的影响及其机制。方法:采用自体内膜移植的方法制备大鼠EMs模型,取30只模型大鼠随机分为模型组、大蒜素(10mg/kg)组和大蒜素(10mg/kg)+LY294002[磷脂酰肌醇3激酶(PI3K)特异性抑制剂,40mg/kg]组,每组10只;另取10只大鼠设为假手术组。各组分别1次/d腹腔注射给药(假手术组和模型组给予生理盐水),疗程4周。通过卡尺测量子宫内膜异位病灶体积并行盆腔粘连评分;HE染色法行子宫内膜病理学检查;ELISA法检测异位病灶组织中肿瘤坏死因子-α(TNF-α)、白细胞介素-1β(IL-1β)、白细胞介素-6(IL-6)、干扰素γ(IFN-γ)含量,生化分析法检测丙二醛(MDA)含量和髓过氧化物酶(MPO)、超氧化物歧化酶(SOD)、过氧化氢酶(CAT)活力;Western blot法检测异位病灶组织蛋白激酶B(Akt)、磷酸化Akt(p-Akt)、核因子E2相关因子2(Nrf2)、血红素加氧酶-1(HO-1)、核因子-κB(NF-κB)蛋白表达。结果:与假手术组相比,模型组大鼠子宫内膜异位病灶间质致密、血管明显增生、炎性细胞浸润等改变,异位病灶组织中TNF-α、IL-1β、IL-6、IFN-γ、MDA含量升高且MPO、SOD、CAT活力降低(P<0.01),p-Akt、Nrf2、HO-1蛋白表达下调且p-Akt/Akt降低(P<0.01),NF-κB表达上调(P<0.01)。与模型组相比,大蒜素组和大蒜素+LY294002组子宫内膜异位病灶体积和粘连评分降低(P<0.05或P<0.01),异位病灶上皮细胞脱落、间质疏松、新生血管明显减少;TNF-α、IL-1β、IL-6、IFN-γ、MDA含量降低且MPO、SOD、CAT活力升高(P<0.05或P<0.01);p-Akt、Nrf2、HO-1蛋白表达上调且p-Akt/Akt升高(P<0.01),NF-κB表达下调(P<0.01)。与大蒜素组相比,大蒜素+LY294002组异位病灶体积和粘连评分升高(P<0.01),异位病灶新生血管增多;TNF-α、IL-1β、IL-6、IFN-γ、MDA含量升高而MPO、SOD、CAT活力降低(P<0.01);p-Akt、Nrf2、HO-1蛋白表达下调且p-Akt/Akt降低(P<0.01),NF-κB表达上调(P<0.01)。结论:大�Objective:To investigate the effect of Allicin on endometriosis(EMs)in rats and its mechanism.Methods:The EMs rat model was prepared by auto-internal membrane transplantation,and the 30 model rats were randomly divided into model group,Allicin(10mg/kg)group and Allicin(10mg/kg)+LY294002(PI3K specific inhibitor,40mg/kg)group,n=10;another 10 rats were set as the sham operation group.The drugs were given once daily by intraperitoneal injection in each group(the rats in sham operation group and model group were given normal saline)for 4 weeks.The adhesion scores of endometriosis lesions was detected,the lesion volume was measured by calipers,the endometrium pathological examination was examed by HE staining method,the content of TNF-α,IL-1β,IL-6,IFN-γwere detected by ELISA method,the content of MDA and the activity of MPO,SOD,CAT in endometriosis lesions were detected by biochemical analysis method;the expression of Akt,p-Akt,Nrf2,HO-1,NF-κB were detected by Western blot method.Results:Compared with the sham operation group,the interstitium of endometriosis lesions in the model group is dense,blood vessels are proliferated and inflammatory cell infiltration changes.The contents of TNF-α,IL-1β,IL-6,IFN-γ,MDA in the ectopic lesion tissue were increased and the activities of MPO,SOD,CAT were decreased(P<0.01);the expression of p-Akt,Nrf2,HO-1 were down-regulated and the ratio of p-Akt/Akt was decreased(P<0.01),while the expression of NF-κB was up-regulated(P<0.01).Compared with the model group,the lesion volume and adhesion score were significantly decreased in Allicin group and Allicin+LY294002 group(P<0.05 or P<0.01);ectopic lesions include epithelial cell shedding,interstitial porosity,neovascularization;the content of TNF-α,IL-1β,IL-6,IFN-γ,MDA were decreased while the activities of MPO,SOD,CAT were increased(P<0.05 or P<0.01);the expression of p-Akt,Nrf2,HO-1 were up-regulated and the ratio of p-Akt/Akt was increased(P<0.01),while the expression of NF-κB was down-regulated(P<0.01).Compared with the Alli

关 键 词：大蒜素 子宫内膜异位症 PI3K/Akt/Nrf2通路 炎症 氧化应激 

分 类 号：R73[医药卫生—肿瘤]