温经汤对子宫内膜异位症小鼠TLR4/NF-κB通路的影响研究  

Effect of Wenjing Decoction on TLR4/NF-κB signaling pathway in mice with endometriosis

作　　者：庄梦斐[1] 曹阳[1] 张婷婷[1] 邵燕婷[1] 李盼盼 谭丽[1] ZHUANG Mengfei;CAO Yang;ZHANG Tingting;SHAO Yanting;LI Panpan;TAN Li(Yueyang Hospital of Intergrated Traditional Chinese and Western Medicine,Shanghai University of Traditional Chinese Medicine,Shanghai 200437,China;Shanghai University of Traditional Chinese Medicine,Shanghai 201203,China)

机构地区：[1]上海中医药大学附属岳阳中西医结合医院,上海200437 [2]上海中医药大学,上海201203

出　　处：《现代中西医结合杂志》2023年第2期165-170,176,共7页Modern Journal of Integrated Traditional Chinese and Western Medicine

基　　金：上海市科委青年科技英才杨帆计划项目(19YF1450200);国家自然科学基金面上项目(82074475);国家自然科学基金青年项目(82104906);上海市“十三五”临床重点专科中医妇科建设项目(shslczdzk04501);上海市进一步加快中医药传承创新发展三年行动计划(2021年-2023年)项目[ZY(2021-2023)0302]。

摘　　要：目的观察温经汤对子宫内膜异位症小鼠Toll样受体4(TLR4)/核转录因子κB(NF-κB)信号通路表达的影响,探讨温经汤抑制异位内膜生长的可能作用机制。方法取54只雌性BALB/c小鼠,采用腹腔内注射子宫内膜碎片法建立子宫内膜异位症模型。将建模成功的50只小鼠随机分为5组,每组10只。温经汤低、中、高剂量组分别给予7.97 g/kg、15.93 g/kg、31.85 g/kg温经汤灌胃,西药组给予孕三烯酮0.5 mg/kg灌胃,模型组给予10 mL/kg生理盐水灌胃。另取5只健康雌性BALB/c小鼠作为空白组,给予10 mL/kg生理盐水灌胃。各组小鼠均连续灌胃21 d后处死,收集异位内膜病灶并称重,ELISA法检测血清和腹腔上清液中基质金属蛋白酶2(MMP-2)、基质金属蛋白酶9(MMP-9)含量,RT-PCR法和Western blot法测定异位内膜病灶中TLR4、髓样分化因子88(MyD88)、NF-κB、转录激活蛋白1(AP-1)、血管内皮生长因子(VEGF)、细胞间黏附分子1(ICAM-1)、血管细胞黏附分子1(VCAM-1)的mRNA和蛋白表达情况。结果与模型组比较,温经汤中、高剂量组和西药组异位内膜病灶的重量均明显降低(P均<0.05);温经汤高剂量组和西药组血清和腹腔上清液中MMP-2和MMP-9含量均明显降低(P均<0.05);温经汤中、高剂量组异位内膜病灶中TLR4、MyD88、VEGF、ICAM-1、VCAM-1 mRNA表达量和温经汤各剂量组异位内膜病灶中NF-κB mRNA表达量均明显降低(P均<0.05);温经汤高剂量组异位内膜病灶中TLR4、MyD88、NF-κB、VEGF、ICAM-1、VCAM-1蛋白表达量和温经汤中剂量组异位内膜病灶中TLR4、ICAM-1蛋白表达量均明显降低(P均<0.05)。结论温经汤能够缩小子宫内膜异位症小鼠异位内膜病灶,可能与调控TLR4/NF-κB信号通路,抑制炎症和血管生成有关。Objective It is to observe the effect of Wenjing Decoction on the expression of Toll-like receptor-4(TLR4)/nuclear factor kappa B(NF-κB)signaling pathway in the mice with endometriosis,and to further explore the possible mechanism of Wenjing Decoction in inhibiting the growth of ectopic endometrium.Methods Fifty-four female BALB/c mice were taken in which the endometriosis models were established by intraperitoneal injection of endometrial fragments.The 50 successfully modeled mice were randomly divided into 5 groups,with 10 mice in each group.The low,medium,and high dose groups of Wenjing Tang were given 7.97 g/kg,15.93 g/kg,and 31.85 g/kg Wenjing Tang by gavage,the western medicine group was given 0.5 mg/kg gestrinone by gavage,and the model group was given 10 mL/kg normal saline by gavage.Another 5 healthy female BALB/c mice were taken as the blank group and given 10 mL/kg normal saline by gavage.21 days after the treatment,the mice were sacrificed,and their ectopic endometrial lesions were collected and weighed,the levels of matrix metalloproteinase 2(MMP-2)and matrix metalloproteinase 9(MMP-9)in serum and peritoneal supernatant were detected by ELISA,and the expression of mRNA and protein of TLR4,myeloid differentiation factor 88(MyD88),NF-κB,transcription activating protein 1(AP-1),vascular endothelial growth factor(VEGF),intercellular adhesion molecule 1(ICAM-1),and vascular cell adhesion molecule 1(VCAM-1)in ectopic endometrial lesions were detected by RT-PCR and Western blot methods,respectively.Results Compared with the model group,the weight of ectopic endometrial lesions in the medium-dose,high-dose groups of Wenjing Decoction and western medicine group were decreased significantly(all P<0.05),the levels of MMP-2 and MMP-9 in serum and peritoneal supernatant in the high-dose group of Wenjing Decoction and western medicine group were significantly decreased(all P<0.05),the expression of mRNA of TLR4,MyD88,VEGF,ICAM-1,VCAM-1 in ectopic endometrial lesions in the middle and high dose groups of Wenjing

关 键 词：子宫内膜异位症 温经汤 Toll样受体/核转录因子κB信号通路 小鼠 

分 类 号：R-332[医药卫生]