褪黑素通过NF-κB/NLRP3信号抑制子宫内膜异位症的进展机制研究  

The Mechanism of Melatonin Inhibiting the Progression of Endometriosis Through NF-κB/NLRP3 Signaling Pathway

作　　者：王剑[1] 杨佳澄 高丽娜 李建华 刘倩 王燕侠[1] 蔺茹[1] 吴珍珍[1] 张春花[1] 金玉霞 刘青[1] WANG Jian;YANG Jiacheng;GAO Lina(Maternal and Child Health Research Center,Gansu Provincial Hospital of Maternal and Child Health,Lanzhou Gansu 730050,China;School of Information Engineering and Artificial Intelligence,Lanzhou University of Finance and Economics,Lanzhou Gansu 730000,China)

机构地区：[1]甘肃省妇幼保健院甘肃省中心医院妇幼保健科研中心,甘肃兰州730050 [2]兰州财经大学信息工程与人工智能学院,甘肃兰州730000

出　　处：《实用妇产科杂志》2024年第4期310-315,共6页Journal of Practical Obstetrics and Gynecology

基　　金：甘肃省自然科学基金(编号:21JR11RA166)。

摘　　要：目的:探讨褪黑素(MEL)对子宫内膜异位症(EMT)进展的抑制作用,以及其对核转录因子κB(NF-κB)/核苷酸结合寡聚化结构域样受体蛋白3(NLRP3)信号的调控机制。方法:通过自体子宫内膜皮下种植法构建EMT大鼠。动物实验模型分假手术组(Sham组,大鼠在造模过程中仅进行子宫片段剪取)和实验处理4组,分别为:模型组(EMT组,大鼠进行自体子宫内膜皮下种植)、褪黑素组(EMT+MEL组,以50 mg/kg的MEL灌胃处理)、EMT+NF-κB信号通路激活剂佛波酯(PMA)组(EMT+PMA组,以5 mg/kg的PMA腹腔注射)、EMT+MEL+PMA组(以50 mg/kg的MEL灌胃处理和5 mg/kg的PMA腹腔注射)。检测各组大鼠子宫内膜异位的质量、血清和腹腔液中肿瘤坏死因子-α(TNF-α)和白细胞介素-6(IL-6)的含量;免疫组化、免疫荧光检测各组样本中髓过氧化物酶(MPO)、血管内皮生长因子(VEGF)的表达;Western blot实验检测各组样本中NF-κB/NLRP3信号通路相关蛋白的表达。结果:与Sham组相比,实验处理4组大鼠中动情周期紊乱的比例、异位子宫内膜的质量、血清以及腹腔液中TNF-α和IL-6的含量、MPO和VEGF的表达及NF-κB/NLRP3信号通路相关蛋白的表达均明显升高,差异均有统计学意义(P<0.05)。与EMT组相比,EMT+MEL组和EMT+MEL+PAM组以上各项指标明显下降,而EMT+PAM组各项指标明显升高;与EMT+MEL组相比,EMT+MEL+PAM组、EMT+PAM组以上各项指标明显升高,以上差异均有统计学意义(P<0.05)。结论:MEL能明显抑制EMT中的炎症反应,抑制EMT的进展,这可能通过抑制NF-κB/NLRP3信号的激活实现的。Objective:To investigate inhibitory effect of melatonin(MEL)on the progression of endometriosis(EMT),and its regulatory mechanism on nuclear factor kappa B(NF-κB)/nucleotide-binding oligomerization domain-like receptors family pyrin domain containing 3(NLRP3)signaling pathway.Methods:EMT rats were established by subcutaneous implantation of autologous endometrium.Animal experimental models were divided into sham surgery group(Sham group,rats only underwent uterine segment cutting during the modeling process),and four experimental treatment groups,as follows:model group(EMT group,rats underwent subcutaneous implantation of autologous endometrium),melatonin group(EMT+MEL group,rats were treated with 50 mg/kg of MEL by gavage),and EMT+NF-κB signaling pathway activator phorbol ester(PMA)group(EMT+PMA group,rats were injected intraperitoneally with 5 mg/kg PMA),EMT+MEL+PMA group(rats were treated by gavage with 50 mg/kg MEL and intraperitoneal injection with 5 mg/kg PMA).The quality of endometriosis of rats,and the content of tumor necrosis factorα(TNF-α)and interleukin-6(IL-6)in the serum and peritoneal fluid in each group was detected.Immunohistochemistry and immunofluorescence were used to detect the expression of myeloperoxi-dase(MPO)and vascular endothelial growth factor(VEGF).Western blot assay was used to detect the expression of NF-κB/NLRP3 signaling pathway in tissue samples.Results:Compared with Sham group,the proportion of estrous cycle disorder,the quality of ectopic endometrium,the content of TNF-αand IL-6 in serum and peritoneal fluid,the expression of MPO and VEGF,in EMT,EMT+MEL,EMT+PAM and EMT+MEL+PAM groups,the expressions of NF-κB/NLRP3 signaling pathway were increased significantly(P<0.05).Compared with EMT group,the above indicators in the EMT+MEL group and EMT+MEL+PAM group decreased significantly,while the indicators in the EMT+PAM group increased significantly.Compared with the EMT+MEL group,the above indicators in the EMT+MEL+PAM group and EMT+PAM group were significantly increased.The d

关 键 词：褪黑素 子宫内膜异位症 核转录因子-κB/核苷酸结合寡聚化结构域样受体蛋白3信号通路 

分 类 号：R711.71[医药卫生—妇产科学]