目的 基于脂肪酸结合蛋白4（FABP4）/过氧化物酶体增殖物激活受体γ（PPARγ）/核因子κB（NF-κB）信号通路探讨三棱莪术配伍治疗子宫内膜异位症（EMS）的机制。方法 对SPF级雌性SD大鼠采用自体子宫内膜移植法构建EMS模型，B超观察异位病灶的生长情况。将造模成功的大鼠随机分为模型组、三棱组（三棱配方颗粒，生药20 g·kg^-1）、莪术组（莪术配方颗粒，生药20 g·kg^-1）和三棱-莪术配伍组（三棱-莪术等比配伍，生药20 g·kg^-1），另设假手术组，每组10只。各组大鼠ig相应药物或蒸馏水，连续8周。末次给药后，分别通过小动物超声仪和肉眼观察、卡尺测量异位病灶，并计算体积；苏木精-伊红（HE）染色法观察病灶组织病理形态；酶联免疫吸附法（ELISA）检测大鼠腹腔液中白细胞介素1β（IL-1β）、IL-6和肿瘤坏死因子-α（TNF-α）含量；免疫荧光法检测子宫内膜和异位病灶中FABP4的平均荧光强度、PPARγ的平均荧光强度和核内平均荧光强度；实时荧光定量PCR（qRT-PCR）技术检测子宫内膜和异位病灶中FABP4、基质金属蛋白酶9（MMP-9）和血管内皮生长因子（VEGF）的mRNA表达； Western blotting技术检测子宫内膜和异位病灶中FABP4、MMP-9和VEGF的蛋白表达及NF-κB p65的磷酸化水平。结果 与假手术组比较，模型组大鼠肉眼可见异位病灶呈透明囊状，内部有积液，表面及周围血管附着丰富； HE染色显示，异位子宫内膜上皮组织产生大量炎症细胞，上皮细胞和基质细胞较为密集，细胞核较大，胞浆丰富，腺体较少，血管丰富；大鼠腹腔液中IL-1β、IL-6和TNF-α含量明显升高，异位病灶中FABP4的平均荧光强度和PPARγ的核内平均荧光强度显著增强，异位病灶中FABP4、MMP-9、VEGF的mRNA和蛋白表达均明显上调，NF-κB p65的磷酸化水平明显升高（P＜0.05）。与模型组比较，三棱组、莪术组和配伍组大鼠病理变化均明显改善，异位病灶的体积均显著减小，腹腔液中IL-1β、IL-6和TNF-α含量明显降低，异位病灶中FABP4的平均荧光强度和PPARγ的核内平均荧光强度显著减弱，异位病灶中FABP4、MMP-9和VEGF的mRNA和蛋白表达均明显下调，NF-κB p65的磷酸化水平明显降低（P＜0.05）。配伍组的异位病灶体积明显小于三棱组和莪术组，腹腔液中IL-1β的含量较莪术组降低，FABP4的平均荧光光强度和mRNA表达均明显弱于三棱组和莪术组，MMP-9 mRNA表达明显低于三棱组，MMP-9的蛋白表达明显低于莪术组（P＜0.05）。结论 三棱莪术可通过相须配伍对EMS产生改善作用，其机制可能与调控FABP4/PPARγ/NF-κB信号通路有关。

Objective To explore the mechanism of treatment of endometriosis (EMS) with the combination of Sparganium stoloniferum and Curcuma kwangsiensis based on the fatty acid-binding protein 4 (FABP4)/peroxisome proliferator-activated receptor γ (PPARγ)/nuclear factor-κB (NF-κB) signaling pathway. Methods EMS models were constructed in SPF-grade female SD rats using the autologous endometrial transplantation method, and ultrasound was used to observe the growth of ectopic lesions. Rats with successful modeling were randomly divided into model group, S. stoloniferum (Sparganii Rhizoma formula granules, 20 g crude drug·kg^-1) and C. kwangsiensis (Curcumae Rhizoma formula granules, 20 g crude drug·kg^-1), and combination group (S. stoloniferum and C. kwangsiensis combined in equal proportion, 20 g crude drug·kg^-1), with another sham surgery group, 10 rats in each group. Each group of rats was ig administered drug or distilled water for 8 consecutive weeks. After the last administration, the ectopic lesions were observed and measured by ultrasound instrument and eye, and the volumes were calculated. The pathological morphology of the lesion tissues was observed by hematoxylin-eosin staining (HE). The contents of interleukin-1β (IL-1β), IL-6 and tumor necrosis factor- α (TNF-α) in the peritoneal fluid of rats were detected by enzyme-linked immunosorbent assay (ELISA). The average fluorescence intensity of FABP4, PPARγ and the average nuclear fluorescence intensity of PPARγ in the endometrium and ectopic lesions were detected by immunofluorescence. The mRNA expressions of FABP4, matrix metalloproteinase 9 (MMP9) and vascular endothelial growth factor (VEGF) in the endometrium and ectopic lesions were detected by real-time fluorescence quantitative polymerase chain reaction (qRT-PCR). The protein expressions of FABP4, MMP9 and VEGF and the phosphorylation level of NF-κB p65 in the endometrium and ectopic lesions were detected by Western blotting. Results Compared with the sham operation group, the macroscopically visible ectopic lesions in the model group rats presented as transparent cysts with internal fluid accumulation, and abundant vascular attachments on the surface and surrounding areas. HE staining revealed that the ectopic endometrial epithelial tissue produced a large number of inflammatory cells, with dense epithelial and stromal cells, large nuclei, abundant cytoplasm, fewer glands, and abundant blood vessels; The contents of IL-1β, IL-6 and TNF-α in the peritoneal fluid of rats in the model group were significantly increased, the average fluorescence intensity of FABP4 and the average nuclear fluorescence intensity of PPARγ in ectopic lesions were significantly enhanced, the mRNA and protein expressions of FABP4, MMP9 and VEGF in ectopic lesions were significantly upregulated, the phosphorylation level of NF-κB p65 was significantly increased (P<0.05). Compared with the model group, the volumes of ectopic lesions in the S. stoloniferum, C. kwangsiensis and combination group were significantly reduced, the contents of IL-1β, IL-6 and TNF-α in peritoneal fluid were significantly decreased, the average fluorescence intensity of FABP4 and the average nuclear fluorescence intensity of PPARγ in the ectopic lesions were significantly weakened, the mRNA and protein expressions of FABP4, MMP9 and VEGF in ectopic lesions were significantly downregulated, and the phosphorylation level of NF-κB p65 was significantly decreased (P<0.05). The volume of ectopic lesions in the compatibility group was significantly smaller than that in the S. stoloniferum group and the C. kwangsiensis group. The content of IL-1β in peritoneal fluid was lower than that in the C. kwangsiensis group. Both the average fluorescence intensity and mRNA expression of FABP4 were significantly weaker than those in the S. stoloniferum group and the C. kwangsiensis group. The expression of MMP9 mRNA was significantly lower than that in the S. stoloniferum group, and the protein expression of MMP9 was significantly lower than that in the C. kwangsiensis group (P<0.05). Conclusion The improvement effect of combination of S. stoloniferum and C. kwangsiensis on EMS may be related to the regulation of the FABP4/PPARγ/NF-κB signaling pathway.

国家自然科学基金资助项目（81803822）；河北省自然科学基金资助项目（H2020999222）；山东省中医药管理局计划项目（2020M198）；河北省中医药管理局科研计划项目（2022066）