不同剂量内异膏对子宫内膜异位症大鼠异位子宫内膜NLRP3炎症小体介导的炎症信号通路的影响  

Effects of Different Doses of Neiyi Ointment on NLRP3 Inflammasome-Mediated Inflammatory Signaling Pathways in Rat Model of Endometriosis

作　　者：陈映 刘丽丽 区绮欣 许焕英 陈玉 邬素珍 CHEN Ying;LIU Li-li;OU Qi-xin;XU Huan-ying;CHEN Yu;WU Su-zhen(Foshan Clinical Medical School,Guangzhou University of Chinese Medicine,Foshan Guangdong 528000;Foshan Fos-un Chancheng Hospital,Foshan Guangdong 528000)

机构地区：[1]广州中医药大学佛山临床医学院,广东佛山528000 [2]佛山复星禅诚医院,广东佛山528000

出　　处：《世界中西医结合杂志》2023年第10期1989-1994,共6页World Journal of Integrated Traditional and Western Medicine

基　　金：佛山市科技创新项目——佛山市中西医结合防治子宫内膜异位症研究平台(2016AG100531);佛山市科技创新项目——佛山市膏方制作工艺及临床应用研究平台(2017AG100211)。

摘　　要：目的探讨不同剂量内异膏对子宫内膜异位症(Endometriosis,EMs)大鼠异位子宫内膜NLRP3炎症小体及其下游炎性因子的影响。方法将38只SPF级健康雌性SD大鼠采用随机数字表法分为假手术组和造模组,造模组大鼠采用自体移植法制备EMs大鼠模型,假手术组仅行开关腹操作,4周后验证模型,随后将造模成功的大鼠用随机数字表法分为模型组、内异膏低剂量组6.5 g/(kg·d)、内异膏中剂量组13 g/(kg·d)、内异膏高剂量组26 g/(kg·d)、地诺孕素组0.21 mg/(kg·d)。各组连续灌胃给药4周,实验结束后,采集异位内膜组织进行苏木素-伊红染色(HE)观察大鼠子宫内膜组织病理形态学变化,实时荧光定量聚合酶链式反应(qRT-PCR)检测异位病灶NLRP3、Caspase-1 mRNA转录水平,酶联免疫吸附测定法(ELISA)检测大鼠腹腔液白介素-18(Interleukin-18,IL-18)水平,以探讨内异膏的治疗机制。结果与假手术组比较,EMs模型组大鼠的异位内膜组织出现病理学改变,异位病灶中NLRP3、Caspase-1 mRNA的表达明显上调,差异有统计学意义(P<0.05),腹腔液中IL-18含量增加;与模型组比较,各给药组大鼠异位内膜组织病理学改变得到改善,内异膏高剂量组可有效降低异位病灶组织NLRP3、Caspase-1 mRNA的表达及腹腔液中IL-18的含量,差异有统计学意义(P<0.05)。结论高剂量内异膏可能通过调控NLRP3炎症小体的激活,抑制炎性因子IL-18的释放,从而缓解EMs大鼠炎症反应。Objective To observe the effects of different doses of Neiyi Ointment on the NOD-like receptor pro⁃tein3(NLRP3)inflammasome and its downstream inflammatory cytokines in the rat model of endometriosis(EMs).Meth⁃ods Thirty-eight SPF-grade healthy female SD rats were assigned by the random number table method into a sham op⁃eration group and a modeling group.The rat model of EMs was established by autologous transplantation method in the modeling group,and the rats in the sham operation group only underwent abdominal opening and closure.The modeled rats were verified 4 weeks later.The successfully modeled rats were assigned by the random number table method into model,low-,medium-,and high-dose[6.5,13,and 26 g/(kg·d),respectively]Neiyi Ointment,and dienogest 0.21 mg/(kg·d)groups.The rats in each group were administrated with corresponding drugs by gavage for 4 consecutive weeks.At the end of the experiment,the ectopic endometrial tissue was stained with hematoxylin-eosin(HE)for observation of his⁃topathological changes.Real-time fluorescence quantitative polymerase chain reaction(qRT-PCR)was employed to de⁃termine the transcript levels of NLRP3 and cysteinyl aspartate specific proteinase 1(caspase-1)in ectopic lesions,and en⁃zyme-linked immunosorbent assay(ELISA)to measure the level of interleukin-18(IL-18)in the peritoneal fluid.Re⁃sults Compared with the sham operation group,the model group showed pathological changes in the ectopic endometrial tissue,up-regulated mRNA levels of NLRP3 and caspase-1 in the lesions(P<0.05),and elevated IL-18 level in the peritoneal fluid.Compared with the model group,drug administration mitigated the pathological changes in the ectopic en⁃dothelial tissue.Furthermore,high-dose Neiyi Ointment down-regulated the mRNA levels of NLRP3 and caspase-1 in the lesions and lowered the IL-18 level in the peritoneal fluid(P<0.05).Conclusion High doses of Neiyi Ointment maybe alleviate the inflammation in the rat model of EMs by regulating the activation of NLRP3 inflammasomes

关 键 词：内异膏 子宫内膜异位症 动物模型 NLRP3炎症小体 炎性因子 

分 类 号：R285.5[医药卫生—中药学]