益母草碱对LPS诱导小鼠子宫内膜炎的抗炎作用研究

doi:10.16431/j.cnki.1671-7236.2023.05.041

摘要/Abstract

摘要： 【目的】探究益母草碱对脂多糖(LPS)诱导小鼠子宫内膜炎的抗炎作用。【方法】将60只6~8周龄雌性C57小鼠随机分为6组:空白对照组,模型组,益母草碱低、中、高剂量组及地塞米松阳性对照组,每组10只。空白对照组经阴道灌注50 μL PBS缓冲液,其余组经阴道灌注50 μL LPS(1 mg/mL)建立小鼠子宫内膜炎疾病模型。造模后,益母草碱低、中、高剂量组分别腹腔注射7.5、15.0、30.0 mg/kg益母草碱,阳性对照组腹腔注射5.0 mg/kg地塞米松,每6 h 1次,连续3次。造模24 h后处死小鼠,测定各组小鼠子宫指数;通过HE染色观察子宫组织病理变化;采用ELISA法检测子宫组织白细胞介素-1β(IL-1β)、IL-6和肿瘤坏死因子-α(TNF-α)等相关炎症因子含量及髓过氧化物酶(MPO)活性。【结果】与空白对照组相比,模型组小鼠子宫指数、子宫组织中炎性细胞因子TNF-α、IL-1β、IL-6含量与MPO活性均极显著升高(P＜0.01);与模型组相比,不同剂量益母草碱能不同程度降低LPS诱导子宫内膜炎小鼠的子宫指数、子宫组织中炎性细胞因子TNF-α、IL-1β、IL-6含量与MPO活性(P<0.01),并呈剂量依赖性;与模型组相比,阳性对照组小鼠子宫指数、子宫组织中炎性细胞因子TNF-α、IL-1β、IL-6含量与MPO活性极显著降低(P＜0.01)。【结论】益母草碱可降低LPS诱导子宫内膜炎小鼠子宫指数、TNF-α、IL-1β、IL-6炎性因子含量及MPO活性,减轻炎症症状,显示出良好的抗炎效果。

关键词: 益母草碱; 小鼠; 脂多糖(LPS); 子宫内膜炎; 炎性细胞因子

Abstract: 【Objective】 The aim of this study was to investigate the anti-inflammatory effect of leonurine on lipopolysaccharide (LPS)-induced endometritis in mice.【Method】 Sixty female C57 mice aged 6 to 8 weeks were randomly divided into 6 groups:Blank control group,model group,leonuri low-dose,medium-dose and high-dose groups and dexamethasone positive control group,with 10 mice in each group.Mice in the blank control group was injected with 50 μL PBS buffer vaginally, and the other groups were injected with 50 μL LPS (1 mg/mL) vaginally to establish an animal model of mouse endometritis. After modeling,the low-dose,medium-dose and high-dose groups were intraperitoneally injected with 7.5,15.0 and 30.0 mg/kg leonurine,respectively,while the positive control group was intraperitoneally injected with dexamethasone at a dose of 5.0 mg/kg,once every 6 hours,for 3 consecutive times.The mice were sacrificed 24 hours after modeling,and the uterine index of each group was calculated.The pathological changes of uterine tissue were observed by HE staining.The contents of interleukin-1β (IL-1β),IL-6 and tumor necrosis factor-α (TNF-α) and the activity of myeloperoxidase (MPO) in uterine tissue were determined by ELISA.【Result】 Compared with blank control group,the uterine index,the contents of inflammatory cytokines TNF-α,IL-1β and IL-6 in uterine tissue and the activity of MPO in model group were extremely significantly increased (P＜0.01).Compared with model group,different doses of leonurine could reduce the uterine index,the contents of inflammatory cytokines TNF-α,IL-1β and IL-6 and the activity of MPO in uterine tissue of LPS-induced endometritis (P<0.01) and showed dose-dependent.Compared with model group,uterine index,contents of inflammatory cytokines TNF-α,IL-1β and IL-6 and MPO activity in positive control group were extremely significantly decreased (P＜0.01).【Conclusion 】 Leonurine could reduce the contents of TNF-α,IL-1β,IL-6 and the activity of MPO in mice with LPS-induced endometritis and alleviate inflammatory symptoms,showing a good anti-inflammatory effect.

Key words: leonurine; mice; lipopolysaccharide (LPS); endometritis; inflammatory cytokines

中图分类号:

S853.7

邵永斌, 郑一闯, 张竞怡, 魏琳颖, 田勇, 孙国结, 刘雨然, 罗燕, 谷新利. 益母草碱对LPS诱导小鼠子宫内膜炎的抗炎作用研究[J]. 中国畜牧兽医, 2023, 50(5): 2149-2155.

SHAO Yongbin, ZHENG Yichuang, ZHANG Jingyi, WEI Linying, TIAN Yong, SUN Guojie, LIU Yuran, LUO Yan, GU Xinli. Study on the Anti-inflammatory Effect of Leonurine on LPS-induced Endometritis in Mice[J]. China Animal Husbandry and Veterinary Medicine, 2023, 50(5): 2149-2155.

参考文献

[1] DENIS-ROBICHAUD J,DUBUC J.Determination of optimal diagnostic criteria for purulent vaginal discharge and cytological endometritis in dairy cows[J].Journal of Dairy Science,2015,98(10):43-48.
[2] SIEMIENIUCH M J,KOZDROWSKI R,SZOSTEK-MIODUCHOWSKA A Z,et al.Evidence for increased content of PGF 2α,PGE 2,and 6-keto-PGF 1α in endometrial tissue cultures from heavy draft mares in anestrus with endometritis[J].Journal of Equine Veterinary Science,2019,77:107-113.
[3] NASRELDIN N,ALI F A Z,ABD-ELHAFEEZ H H,et al.Characterization of immunological,biochemical and inflammatory response of clinical and subclinical endometritis in ewes in the subtropics[J].Animal Reproduction Science,2020,219:106541.
[4] HUSSEN J,SHAWAF T,AI-MUBARAK A I A,et al.Leukocyte populations in peripheral blood of dromedary camels with clinical endometritis[J].Animal Reproduction Science,2020,222:106602.
[5] ENGLAND G C W,RIJSSELAERE T,CAMPBELL A,et al.Normal and abnormal response to sperm deposition in female dogs:A review and new hypotheses for endometritis[J].Theriogenology,2021,159:176-183.
[6] BULC M,CALKA J,MELLER K,et al.Endometritis affects chemical coding of the dorsal root ganglia neurons supplying uterus in the sexually mature gilts[J].Research in Veterinary Science,2019,124:417-425.
[7] WU H C,ZHAO G,JIANG K F,et al.Plantama joside ameliorates lipopolysaccharide-induced acute lung injury via suppressing NF-κB and MAPK activation[J].International Immunopharmacology,2016,35:315-322.
[8] WU H C,ZHAO G,JIANG K F,et al.Puerarin exerts an antiinflammatory effect by inhibiting NF-kB and MAPK activation in staphylococcus aureus-induced mastitis[J].Phytotherapy Research,2016,30(10):1658-1664.
[9] LIANG Y J,SHEN T,MING Q,et al.Alpinetin ameliorates inflammatory response in LPS-induced endometritis in mice[J].International Immunopharmacology,2018,62:309-312.
[10] SAYED A,ALAM A,ISLAM S,et al.Leonurus sibiricus L.(honeyweed):A review of its phytochemistry and pharmacology[J].Asian Pacific Journal of Tropical Biomedicine,2016,6(12):1076-1080.
[11] MIAO L L,ZHOU Q M,PENG C,et al.Leonurus japonicus(Chinese motherwort),an excellent traditional medicine for obstetrical and gynecological diseases:A comprehensive overview[J].Biomedicine&Pharmacotherapy,2019,117:109060.
[12] SUN K,LUO J,GUO J,et al.The PI3K/Akt/mTOR signaling pathway in osteoarthritis:A narrative review[J].Osteoarthritis and Cartilage,2020,28:400-409.
[13] XU D,CHEN M,REN X,et al.Leonurine ameliorates LPS-induced acute kidney injury via suppressing ROS-mediated NF-κB signaling pathway[J].Fitoterapia,2014,97:148-155.
[14] LI N,XU Q,LIU Q P,et al.Leonurine attenuates fibroblast-like synoviocyte-mediated synovial inflammation and joint destruction in rheumatoid arthritis[J].Rheumatology (Oxford,England),2017,56(8):1417-1427.
[15] SONG X J,WANG T C,ZHANG Z C,et al.Leonurine exerts anti-inflammatory effect by regulating inflammatory signaling pathways and cytokines in LPS-induced mouse mastitis[J].Inflammation,2015,38(1):79-88.
[16] 张积仁,郑静芬.炎症因子与慢病防控[M].北京:科学出版社,2019. ZHANG J R,ZHENG J F.Inflammatory Factors and Chronic Disease Prevention and Control[M].Beijing:Science Press,2019.(in Chinese)
[17] 赵欣,王莹,李春亭,等.蒲公英提取物对LPS诱导小鼠乳腺炎的减轻效应及其机制分析[J].畜牧兽医学报,2022,53(8):2773-2781. ZHAO X,WANG Y,LI C T,et al.Effects of dandelion extract on LPS-induced mastitis in mice and its mechanism analysis[J].Chinese Journal of Animal Science and Veterinary Medicine,2022,53(8):2773-2781.(in Chinese)
[18] 张玉珠,于超,郑慧华,等.原儿茶酸对LPS诱导的小鼠子宫内膜炎的作用机制研究[J].中国畜牧兽医,2022,49(4):1585-1591. ZHANG Y Z,YU C,ZHENG H H,et al.Mechanism study of protocatechuic acid on LPS-induced endometritis in mice[J].China Animal Husbandry&Veterinary Medicine,2022,49(4):1585-1591.(in Chinese)
[19] WU H C,DAI A L,CHEN X X,et al.Leonurine ameliorates the inflammatory responses in lipopolysaccharide-induced endometritis[J].International Immunopharmacology,2018,61:156-161.
[20] KOLAROVE H,VITECEK J,CERNA A,et al.Myeloperoxidase mediated alteration of endothelial function is dependent on its cationic charge[J].Free Radical Biology and Medicine,2021,162:14-26.
[21] WANG J,WANG W W,PANG Y T.Saikosaponin a inhibits LPS-induced endometritis in mice through activating Nrf2 signaling pathway[J].Inflammation,2018,41(4):1508-1514.