醋酸甲羟孕酮联合甲硝唑对子宫内膜炎大鼠炎性因子及TLR4NF-κB通路的影响

Effects of medroxyprogesterone acetate combined with metronidazole on inflammatory factors and TLR4/NF-κB pathway in rats with endometritis

目的研究醋酸甲羟孕酮联合甲硝唑对子宫内膜炎大鼠炎性因子及TLR4/NF-κB信号通路的影响。方法将40只SPF级SD大鼠随机分为5组,每组8只。空白组不做处理,其余4组均先构建子宫内膜炎大鼠模型,造模成功后的第2天起,模型组(不给药),其余3个组(醛酸甲羟孕酮组、甲硝唑组、联合用药组)分别按醋酸甲羟孕酮(4 mg·kg^-1·d-1)、甲硝唑(0.02 g·kg^-1·d-1)、醋酸甲羟孕酮联合甲硝唑(4 mg·kg^-1·d-1+0.02 g·kg^-1·d-1)灌胃治疗,连续14 d后处死,采样待检。HE染色观察子宫组织病理学变化;免疫组化检测子宫组织MMP-2、MMP-9表达;ELISA检测血清IL-1、PGE2、MDA、NO、SOD水平;Western Blot检测子宫组织NF-κB p65、TLR4表达。结果不同给药组均可减轻子宫内膜炎大鼠子宫组织病理损伤;与空白组比较,模型组大鼠IL-1、PGE2、MDA、NO、NF-κB p65、TLR4表达明显升高,SOD、MMP-2、MMP-9表达明显降低(均P<0.05);与模型组比较,联合用药可明显降低子宫内膜炎大鼠IL-1、PGE2、MDA、NO、NF-κB p65、TLR4表达,明显升高SOD、MMP-2、MMP-9表达,且联合用药组IL-1表达明显低于甲硝唑组,TLR4表达明显低于醋酸甲羟孕酮组及甲硝唑组,MMP-2表达明显高于甲硝唑组,MMP-9表达明显高于醋酸甲羟孕酮组及甲硝唑组(均P<0.05)。结论醋酸甲羟孕酮联合甲硝唑通过影响TLR4/NF-κB信号通路,改善炎性指标,发挥对子宫内膜炎大鼠的治疗作用。

Objective To study the effects of medroxyprogesterone acetate combined with metronidazole on inflammatory factors and TLR4/NF-κB signaling pathway in rats with endometritis.Methods Forty healthy SD rats were randomly divided into 5 groups.The control group was not treated.The other 4 groups were induced to model rat endometritis.On the second day after the successful modeling,the three groups were treated with medroxyprogesterone acetate(4 mg/kg/d),metronidazole(0.02 g/kg/d),medroxyprogesterone acetate and metronidazole(4 mg/kg/d+0.02)g/kg/d)was administered by gavage.After 14 consecutive days,the rats were sacrificed and samples were taken for examination.The pathological changes of uterus were examined by HE staining.The expressions of MMP-2 and MMP-9 in uterus were detected by immunohistochemistry.The levels of serum IL-1,PGE2,MDA,NO and SOD were detected by ELISA.WB detected the expression of NF-κB p65,TLR4 in uterus.Results Different administration groups could alleviate the pathological damage of uterus in rats with endometritis.Compared with the control group,the expression of IL-1,PGE2,MDA,NO,NF-κB p65 and TLR4 in the model group was significantly increased,while the expression of SOD,MMP-2 and MMP-9 were significantly reduced(P<0.05).Compared with the model group,the combined use can significantly reduce the expression of IL-1,PGE2,MDA,NO,NF-κB p65 and TLR4 in endometritis rats,and significantly increase the expression of SOD,MMP-2 and MMP-9.The expression of IL-1 in the combined medication group was significantly lower than that in the metronidazole group.The TLR4 expression was significantly lower than that in the medroxyprogesterone acetate group and metronidazole group.The MMP-2 expression was significantly higher than that in the metronidazole group,and MMP-9 expression was significantly higher than that in medroxyprogesterone acetate group and metronidazole group(P<0.05).Conclusion Medroxyprogesterone acetate combined with metronidazole has obvious therapeutic effect on endometritis in rats,affect TLR4/NF-κB signaling pathway,improve inflammatory index and exert therapeutic effect on endometritis rats.