芒柄花黄素对脓毒症小鼠炎性反应及MAPK/NF-κB通路影响的实验研究  

Effects of formononetin on inflammatory response and MAPK/NF-κB pathway in septic mice

作　　者：魏东梅 邵龙刚[1] WEI Dongmei;SHAO Longgang(Department of Emergency and Critical Medicine,the Second Hospital of Jiangsu Traditional Chinese Medicine,Nanjing 210019,China)

机构地区：[1]江苏省第二中医院急危重症医学科,江苏南京210019

出　　处：《陕西医学杂志》2023年第5期503-507,共5页Shaanxi Medical Journal

基　　金：江苏省中医药科技发展计划面上项目(MS2022036);南京中医药大学自然科学基金资助项目(XZR2020052)。

摘　　要：目的:探究芒柄花黄素对脓毒症小鼠炎性反应的作用及机制。方法:利用随机数法将40只小鼠随机分为四组,在小鼠腹腔注射脂多糖建立脓毒症模型(内毒素组),在给予脂多糖小鼠中分别按照10 mg/kg(低剂量组)和20 mg/kg(高剂量组)腹腔注射芒柄花黄素,对照组给予等量0.9%氯化钠溶液。观察各组小鼠存活率,并预测腹腔灌洗液白细胞计数;利用试剂盒检测小鼠脾脏中的炎症指标,并对脾脏染色后观察其损伤程度;利用免疫印迹技术检测相关通路蛋白表达。结果:芒柄花黄素能够提高脓毒症小鼠的存活率(P<0.05);芒柄花黄素降低了脓毒症小鼠腹腔灌洗液中的白细胞(白细胞总数、巨噬细胞、中性粒细胞和淋巴细胞)计数(均P<0.05)和脾脏中的炎症指标(C-反应蛋白、单核细胞趋化蛋白-1、髓过氧化物酶活性、白细胞介素-1β、白细胞介素-6和肿瘤坏死因子-α)(均P<0.05);芒柄花黄素缓解了脓毒症小鼠脾脏白髓周围巨噬细胞的浸润,减少了脾脏的坏死细胞和凋亡小体;芒柄花黄素降低了丝裂原活化蛋白激酶和核因子-κB通路中关键分子的表达量(均P<0.05)。结论:芒柄花黄素可能通过抑制丝裂原活化蛋白激酶和核因子-κB通路活化减轻小鼠脓毒症炎性反应。Objective:To explore the role and mechanism of formononetin in inflammatory response in septic mice.Methods:A total of 40 mice were randomly divided into four groups.The model of sepsis was established by intraperitoneal injection of LPS(LPS group).In mice given LPS,10 mg/kg(low dose group)or 20 mg/kg(high dose group)were intraperitoneally injected with formononetin,whereas the control group was given the same amount of 0.9%sodium chloride solution.The survival rate of mice in each group was observed,and the white blood cell count of peritoneal lavage fluid was predicted.The inflammatory indicators in the spleen of mice were detected by the kit,and the degree of injury was observed after spleen staining.Western blot was used to detect the protein expression of related pathways.Results:Formononetin could improved the survival rate of septic mice(P<0.05).Formononetin reduced the number of white blood cells(total white blood cells,macrophages,neutrophils and lymphocytes)in peritoneal lavage fluid and inflammatory indicators in spleen(C-reactive protein,monocyte chemoattractant protein-1,myeloperoxidase activity,interleukin-1β,Interleukin-6 and tumor necrosis factor-α)of septic mice(all P<0.05).Formononetin alleviated the infiltration of macrophages around the white pulp of the spleen and reduced the number of necrotic cells and apoptotic bodies in the spleen.Formononetin reduced the expression of key molecules in mitogen activated protein kinase(MAPK)and nuclear factor-κB(NF-κB)pathway(all P<0.05).Conclusion:Formononetin may alleviate inflammatory response via MAPK/NF-κB pathways in septic mice.

关 键 词：芒柄花黄素 脓毒症 炎性反应 炎症因子 信号通路 小鼠 

分 类 号：R631.1[医药卫生—外科学]