基于miR-451a/p38MAPK通路研究柴胡清肝汤干预肉芽肿性小叶性乳腺炎大鼠的机制  

Mechanism study of Chaihu Qinggan Decoction intervention in granulomatous lobular mastitis rats based on miR-451a/p38MAPK pathway

作　　者：苏靖群 凌洁 李恋 熊帆 丁笑 刘清 王华[1] 刘丽芳[1] SU Jingqun;LING Jie;LI Lian(The First Affiliated Hospital of Hunan University of Chinese Medicine,Hunan,Changsha 410007,China;Hunan Hospital of Integrated Traditional Chinese and Western Medicine,Hunan,Changsha,410006,China)

机构地区：[1]湖南中医药大学第一附属医院,湖南长沙410007 [2]湖南省中西医结合医院,湖南长沙410006

出　　处：《四川中医》2025年第2期105-111,共7页Journal of Sichuan of Traditional Chinese Medicine

基　　金：湖南省中医药科研计划项目(编号:202100);湖南省中医药管理局“十四五”第一批中医药领军人才培养项目(编号:rsk-023~02);湖南中医药大学校级科研基金(编号:2022CX139、2023CX91)。

摘　　要：目的:探讨柴胡清肝汤对肉芽肿性小叶性乳腺炎(GLM)大鼠miR-451a/p38MAPK通路的调控作用。方法:建立GLM大鼠模型,60只大鼠随机分为正常组、模型组、中药低、中、高剂量组、激素组。计算乳腺炎症指数;HE染色法观察乳腺组织病理学变化;Western blot和RT-PCR法检测乳腺组织MKK3、p-p38MAPK、p38MAPK蛋白及miR-451a、p38MAPK、MKK3mRNA的表达水平;ELISA法检测血清CRP、IL-8、IL-2水平。结果:与正常组比较,模型组大鼠乳腺炎症指数显著升高(P<0.01),病理学上形成了肉芽肿结构、伴多种炎性细胞浸润,大鼠乳腺组织中的miR-451a、MKK3、p-p38MAPK、p38MAPK表达升高(P<0.01),血清中的IL-2、IL-8、CRP含量升高(P<0.01);与模型组比较,中药中、高剂量组及激素组均能降低乳腺炎症指数(P<0.01),减轻乳腺组织病理学损伤及炎性细胞浸润,降低乳腺组织miR-451a、MKK3、p-p38MAPK、p38MAPK表达水平(P<0.05),降低血清IL-2、IL-8、CRP含量(P<0.01)。结论:柴胡清肝汤可能通过调控miR-451a/p38MAPK通路抑制炎症因子的释放,减少炎症损伤,从而发挥抑制GLM炎症反应的治疗作用。Objective:Investigate the regulatory impact of Chaihu Qinggan Decoction on the miR-451a/p38MAPK pathway in granulomatous lobular mastitis(GLM)rats.Methods:A GLM rat model was established,and 60rats were randomly divided into normal group,model group,low-,medium-,high-dose groups of traditional Chinese medicine,and hormone group.The breast inflammation index was calculated,and the histopathological changes of the breast were observed by HE staining.Western blot and qRT-PCR were used to detect the expression levels of MKK3,p-p38MAPK,p38MAPK protein and miR-451a,p38MAPK,MKK3mRNA in breast tissue.Serum CRP,IL-8and IL-2levels were detected by ELISA.Results:Compared with the normal group,the mammary inflammation index of the model group was significantly increased(P<0.01),the structure of granuloma was pathologically formed with a variety of inflammatory cell infiltration,the expression of miR-451a,MKK3,pp38MAPK and p38MAPK in mammary tissue was increased(P<0.01),and the contents of IL-2,IL-8and CRP in serum were increased(P<0.01).Compared with the model group,the middle-dose and high-dose groups and the hormone group could reduce the breast inflammation index(P<0.01),alleviate the histopathological damage and inflammatory cell infiltration of the breast tissue,reduce the expression levels of miR-451a,MKK3,p-p38MAPK and p38MAPK in breast tissue(P<0.05,P<0.01),and reduce the serum IL-2,IL-8and CRP contents(P<0.01).Conclusion:Chaihu Qinggan Decoction may inhibit the release of inflammatory factors and reduce inflammatory damage by regulating the miR-451a/p38MAPK pathway,thereby exerting a therapeutic effect of inhibiting GLM inflammatory response.

关 键 词：肉芽肿性小叶性乳腺炎 miR-451a P38MAPK 柴胡清肝汤 炎症因子 

分 类 号：R271.9[医药卫生—中西医结合]