欧前胡素通过抑制NLRP3炎性通路改善大鼠慢性子宫内膜炎症

Imperatorin alleviates chronic endometrial inflammation by inhibiting the NLRP3 inflammatory pathway in rats

目的探讨欧前胡素(imperatorin,Imp)对慢性子宫内膜炎(chronic endometritis,CE)的治疗及可能的作用机制。方法采用卵巢处注射苯酚胶浆法建立CE大鼠模型,分为对照组(CT组)、CE组、Imp低剂量组(ImpL组,5 mg∙kg^(-1)∙d^(-1))、Imp高剂量组(ImpH组,10 mg∙kg^(-1)∙d^(-1))、ImpH+脂多糖(LPS,10 mg/kg)组,称量质量检测子宫脏器指数;苏木精-伊红(HE)染色观察子宫组织病理变化;免疫组化检测子宫内膜血管内皮生长因子(VEGF)表达水平;ELISA测定血清白介素(IL)-6、肿瘤坏死因子(TNF-α)的含量;RT-qPCR和Western blot验证子宫组织IL-1β、核因子κB(NF-κB)、NOD样受体热蛋白结构域相关蛋白3(NLRP3)、基质金属蛋白酶(MMP)-9的表达。结果与CT组相比,CE组大鼠子宫和阴道内肿胀、充血,子宫内膜VEGF的表达降低(P<0.05),血清IL-6、TNF-α含量和子宫组织IL-1β、p-NF-κB/NF-κB、NLRP3、MMP-9表达增加(P<0.05);与CE组比较,ImpL、ImpH组大鼠子宫和阴道内结节肿胀、充血均有所缓解,子宫内膜VEGF的表达增加,血清IL-6、TNF-α含量和子宫组织IL-1β、p-NF-κB/NF-κB、NLRP3、MMP-9表达减少(P<0.05);LPS可部分逆转ImpH对CE大鼠的改善作用。结论Imp可能通过抑制NLRP3炎症通路的激活对CE有一定治疗作用。

This study was designed to explore the treatment effect of imperatorin(Imp)on chronic endometritis(CE)and the possible mechanism.A rat model of CE was established by injecting phenol gel into the ovary and was grouped into CE group,Imp low dose group(ImpL group,5 mg∙kg^(-1)∙d^(-1)),Imp high dose group(ImppH group,10 mg∙kg^(-1)∙d^(-1)),and ImpH+lipopolysaccharide(LPS,10 mg/kg)groups,while sham-treated rats were grouped as control group(CT group).Uterine organ index of all groups were measured;hematoxylin eosin(HE)staining was applied to observe the pathological changes of uterine tissue;immunohistochemistry was applied to detect the expression of vascular endothelial growth factor(VEGF)in the endometrium;ELISA was used to measure the levels of serum IL-6 and TNF-α;RT-qPCR and Western blot were applied to verify the expression of IL-1β,nuclear factor-κB(NF-κB),NOD-like receptor protein 3(NLRP3),and matrix metalloproteinase(MMP)-9 in uterine tissue.Compared with the CT group,the uterus and vagina of the CE group were swollen and congested,and the expression of VEGF in the endometrium was decreased(P<0.05),the levels of IL-6 and TNF-αin serum and the expressions of IL-1β,p-NF-κB/NF-κB,NLRP3,and MMP-9 in uterine tissue were increased(P<0.05).Imp could reverse these pathological changes mentioned above in CE model,while LPS was able to partially suppress the improvement effect of ImpH on CE rats.In conclusion,Imp may have a certain therapeutic effect on CE by inhibiting the activation of NLRP3 inflammatory pathway.