摘要
目的 探讨蒙药苏格木勒-7对子宫内膜炎大鼠炎症反应的作用及其机制.方法 以15%苯酚胶浆注入雌性SD大鼠子宫方法建立子宫内膜炎模型.建模成功大鼠随机分为蒙药低剂量(0.8 g/kg)组、蒙药中剂量(1.6 g/kg)组、蒙药高剂量(3.2 g/kg)组、妇科千金胶囊(1.6 g/kg)组、TAK-242(0.3 mg/kg)组、模型组,每组10只;另取10只正常雌性SD大鼠作为对照组,药物干预3周后酶联免疫法检测各组大鼠血清Toll样受体4(TLR4)、肿瘤坏死因子-α(TNF-α)、白细胞介素(IL)-6、IL-1β、单核细胞趋化蛋白-1(MCP-1)水平;HE染色观察各组子宫内膜病理改变并比较病理评分;实时定量PCR(RT-qPCR)检测各组子宫内膜组织中TLR4、核转录因子-κB p65(NF-κB p65)、核因子κB抑制因子α(IκBα)表达;Western blotting检测各组子宫内膜组织TLR4、NF-κB p65、IκBα、p-IκBα表达.结果 与对照组比较,模型组血清炎性细胞因子水平、子宫内膜组织病理改变评分均增高(均P<0.05);子宫内膜组织中TLR4、NF-κB p65、IκBαmRNA和蛋白表达,p-IκBα及p-IκBα/IκBα均增高(均P<0.05).与模型组比较,妇科千金胶囊组、TAK-242组、蒙药各剂量组血清炎性细胞因子水平、子宫内膜组织病理改变评分均降低(均P<0.05);子宫内膜组织中TLR4、NF-κB p65、IκBαmRNA和蛋白表达,p-IκBα及p-IκBα/IκBα均降低(P<0.05).HE染色结果显示,与对照组比较,模型组大鼠子宫内膜组织严重损伤;与模型组比较,妇科千金胶囊组、TAK-242组、蒙药各剂量组子宫内膜组织损伤均减轻.蒙药苏格木勒-7的作用呈剂量依赖性,且蒙药中剂量组与妇科千金胶囊组作用相当.与TAK-242组比较,蒙药高剂量组血清炎性细胞因子水平、子宫内膜组织病理改变评分均降低(均P<0.05),而子宫内膜组织TLR4、NF-κB p65、IκBαmRNA与蛋白表达,p-IκBα及p-IκBα/IκBα水平比较差异无统计学意义(均P>0.05).结论 蒙药苏格木勒-7可减轻子宫内膜炎大鼠子宫内膜组织病理损伤和炎症反应,其作用呈剂量依赖性,其作用机制可能是通过抑制TLR4/NF-κB通路来实现的.
Abstract
Objective To observe the effect of the Mongolian medicine Sugemule-7 on alleviating inflammatory response in rats with endometritis,and to explore whether the drug regulates Toll-like receptor 4(TLR4)/nuclear transcription factor-κB(NF-κB)pathway.Methods Endometritis models were established by injecting 15% phenol glue into the uterus of female SD rats,which were divided into Mongolian medicine low-,medium-and high-dose,metronidazole,TAK-242,and model groups,each with 10 rats.Ten additional normal female SD rats were used as controls.After intervention for 3 weeks,enzyme-linked immunosorbent assay was used for detection of serum TLR4 and tumor necrosis factor-α,interleukin-6,interleukin-1β,and monocyte chemotactic protein-1 levels.Hematoxylin and eosin(HE)staining was used to observe pathological changes in the endometrium,and pathological scores were compared.Real-time quanti-tative PCR was used to detect TLR4 and NF-κB p65,and nuclear factor-κB-inhibitory factorα(IκBα)expressions in endometrial tissues.Western blotting was used to detect TLR4 and NF-κB p65,IκBαand p-IκBαexpressions in endometrial tissues.Results Serum inflam-matory factor levels,endometrial tissue pathological change scores,and endometrial tissue TLR4,NF-κB p65,IκBαmRNA,and protein expressions,p-IκBα and p-IκBα/IκBα levels were higher in the model group(P<0.05)and lower in the metronidazole,TAK-242,and Mongolian medicine low-,medium-,and high-dose groups(P<0.05)than in the control group.HE staining of the uterus and endometrial tissue of the model group rats showed severe damage,and the metronidazole,TAK-242,and Mongolian medicine low-,medium-,and high-dose groups showed relief.The effect of Sugemule-7 was dose-dependent,and the middle-dose group showed similar effects to the metroni-dazole group.The high-dose group had lower serum inflammatory factor levels and endometrial tissue pathological changes than the TAK-242 group(P<0.05),and there was no statistically significant differences in the TLR4,NF-κB p65,IκBαmRNA and protein expressions,p-IκBα,and p-IκBα/IκBα compared with the TAK-242 group(P>0.05).Conclusion The Mongolian medicine Sugemule-7 alleviated the pathological damage and inflammatory response of endometrial tissues in rats with endometritis.Its effect is dose-dependent,and its mechanism of action may be achieved by inhibiting the TLR4/NF-κB pathway.
基金项目
内蒙古自治区自然科学基金(2022MS08073)
内蒙古自治区直属高校基本科研项目(GXKY22241)
万方数据