摘要
目的 探讨灯盏花素注射液(Bre)对大鼠子宫内膜异位症(EMs)的影响,并基于p38MAPK信号通路探讨其机制。方法 将60只雌性大鼠按体重随机分为假手术组、模型组、Bre(1mg·kg^(-1))组、SB202190(p38MAPK抑制剂,15 mg·kg^(-1))组、Bre(1 mg·kg^(-1))+SB202190(15mg·kg^(-1))组,每组12只。除假手术组外,其他4组均采用自体内膜移植法制备EMs大鼠模型。造模完成后,各组分别腹腔注射给药,1次·d^(-1)连续4周。通过超声影像测量异位病灶体积,根据Haber评分标准进行盆腔粘连评分,HE染色法观察异位病灶组织病理改变,酶联免疫吸附法检测炎症因子(TNF-α、IL-6、IL-8)含量,Western blot法检测p38MAPK信号通路相关蛋白p38和p-p38、细胞外信号调节激酶1/2(ERK1/2)、p-ERK1/2、c-Jun氨基末端激酶(JNK)、p-JNK以及核因子-κB p65(NF-κB p65)、p-NF-κB p65、p-IκBα表达。结果 与模型组比较,Bre、SB202190和Bre+SB202190可显著降低EMs大鼠异位病灶体积和盆腔粘连评分(P<0.05);促进异位病灶结构紊乱、间质疏松、上皮细胞坏死、新生血管减少、腺体萎缩、炎性细胞浸润减少等病理改变;显著降低TNF-α、IL-6、IL-8含量,p-p38/p38、(p-ERK1/2)/(ERK1/2)、p-JNK/JNK、p-NF-κB p65/NF-κB p65比值及p-IκBα相对表达量(P<0.05)。Bre+SB202190组上述作用均显著优于Bre组和SB202190组(P<0.05)。结论 Bre可抑制EMs大鼠异位病灶生长、减轻盆腔粘连,其机制可能与抑制p38MAPK信号通路过度激活,进而抑制炎症反应有关。
Objective To determine the effect of Breviscapine injection(Bre)on endometriosis(EMs)in rats,and its mechanism based on p38MAPK signaling pathways.Methods According to body weight,60 female rats were randomly divided into a sham operation group,a model group,a Bre(1 mg·kg^(-1))group,a SB202190(p38MAPK inhibitor,15 mg·kg^(-1))group and a Bre(1 mg·kg^(-1))+SB202190(15 mg·kg^(-1))group,with 12 rats in each group.Except for the sham operation group,in the other 4 groups EMs rat models were established by autologous endomembrane transplantation.After the modeling,each group was intraperitoneally injected corresponding drugs once daily for 4 consecutive weeks.The volume of the ectopic lesions was measured by ultrasound imaging system.The pelvic adhesion was scored according to the Haber scale.The histopathological changes of the ectopic lesions was observed with HE staining.The content of inflammatory factors(TNF-α,IL-6,and IL-8)was detected by enzyme-linked immunosorbent assay.The expression of p38MAPK signaling pathways related proteins p38,p-p38,extracellular signal-regulated kinase 1/2(ERK1/2),p-ERK1/2,c-Jun N-terminal kinase(JNK),p-JNK,and nuclear factor-κB p65(NF-κB p65),p-NF-κB p65,and p-IκBαwere detected by Western blot.Results Compared with the model group,Bre,SB202190 and Bre+SB202190 significantly decreased the ectopic lesion volume and pelvic adhesion score in EM rats(P<0.05),promoted the pathological changes in the ectopic lesions such as structural disorder,interstitial loosening,necrosis and shedding of the epithelial cells,decreased neovascularization and inflammatory cell infiltration,caused gland atrophy,and significantly decreased the content of TNF-α,IL-6,and IL-8,the ratio of p-p38/p38,(p-ERK1/2)/(ERK1/2),p-JNK/JNK,p-NF-κB p65/NF-κB p65 and the relative expression of p-IκBα(P<0.05).The above effects in the Bre+SB202190 group were significantly better than those of the Bre group and the SB202190 group(P<0.05).Conclusion Bre can inhibit the growth of ectopic lesions and reduce pelvic a
作者
姬白嫣
魏娟
JI Bai-yan;WEI Juan(Handan Second Hospital,Handan Hebei 056001)
出处
《中南药学》
CAS
2023年第12期3167-3173,共7页
Central South Pharmacy
基金
河北省医学科学研究课题(No.20191491)。
