白果内酯通过抑制丝裂原活化蛋白激酶/核因子-κB通路减轻脓毒症诱发肝损伤实验研究  

Bilobalide protects against liver injury induced by sepsis via inhibiting activation of MAPK/NF-κB pathways

作　　者：吴建棋 张世安 孙中洋 WU Jianqi;ZHANG Shian;SUN Zhongyang(The No.900 Hospital of PLA,Fuzhou 350025,China)

机构地区：[1]解放军第九〇〇医院,福建福州350025 [2]解放军东部战区空军医院,江苏南京210002

出　　处：《陕西医学杂志》2024年第9期1166-1171,共6页Shaanxi Medical Journal

基　　金：国家自然科学基金资助项目(81600694);福建省自然科学基金资助项目(2023J011346);军委后勤科研项目(CKJ18J019,CKJ20J024,CKJ21J033)。

摘　　要：目的:探讨白果内酯对脓毒症诱发肝损伤的保护作用及机制。方法:利用盲肠结扎穿孔术建立小鼠脓毒症模型。利用随机数字表法将48只小鼠平均分为四组,对照组仅进行假手术,而不进行盲肠结扎;脓毒症组通过盲肠结扎建立脓毒症小鼠模型;低剂量组在建模后尾静脉注射4 mg/kg白果内酯溶液;高剂量组在建模后尾静脉注射12 mg/kg白果内酯溶液。记录各组小鼠7 d的存活率和体重,检测腹腔灌洗液和血液中的菌落形成数量;利用HE染色和高碘酸希夫(PAS)染色方法观察肝损伤情况;检测血清中丙氨酸转氨酶(ALT)和天冬氨酸转氨酶(AST)含量评估肝脏功能;利用试剂盒检测血清和肝脏匀浆中肿瘤坏死因子(TNF)-α、白细胞介素(IL)-6、IL-1β和IL-10;利用免疫组化技术检测中性粒细胞浸润;利用Western blot检测丝裂原活化蛋白激酶(MAPK)/核因子-κB(NF-κB)通路中关键分子表达量。结果:白果内酯提高了脓毒症小鼠的存活率,减少了脓毒症小鼠腹腔灌洗液和血液中的菌落形成数量,并减轻了由脓毒症诱发的肝损伤。白果内酯减轻了脓毒症小鼠的炎症反应及肝脏的中性粒细胞浸润,抑制了脓毒症小鼠肝脏组织中活化的MAPK/NF-κB通路。结论:白果内酯通过抑制MAPK/NF-κB通路活化减轻脓毒症诱发的肝损伤。Objective:To explore the protective effects and mechanism of bilobalide on liver injury induced by sepsis.Methods:The cecal ligation and puncture surgery was used to establish mouse sepsis model.The 48 mice were divided into 4 groups on average using random number table method.The mice in the control group only underwent sham surgery without cecal ligation.The mice in the sepsis group underwent cecal ligation surgery.The mice in the low-dose group received tail vein injection of 4 mg/kg bilobalide solution after cecal ligation surgery.The mice in the high-dose group received tail vein injection of 12 mg/kg bilobalide solution after after cecal ligation surgery.The survival rate and body weight of each group of mice were recorded for 7 days.The number of colony formation in abdominal lavage fluid and blood were detected.The levels of liver injury were observed with HE staining and PAS staining methods.The liver function were evaluated by detecting the levels of ALT and AST in serum.The levels of TNF-α,IL-6,IL-1βand IL-10 in serum and liver homogenate were detected using reagent kits.The neutrophil infiltration was observed by immunohistochemistry.The levels of key molecules in mMAPK/NF-κB pathway were evaluated by Western blot.Results:Bilobalide increased the survival rate,reduced the number of colony formation in the peritoneal lavage fluid and blood and alleviated liver damage induced by sepsis.Bilobalide reduced inflammation and neutrophil infiltration in the liver of septic mice and inhibited the activation of MAPK/NF-κB pathway in the liver tissue of septic mice.Conclusion:Bilobalide protects against liver injury induced by sepsis via inhibiting the activation of MAPK/NF-κB pathways.

关 键 词：脓毒症 白果内酯 存活率 肝损伤 炎症反应 信号通路 

分 类 号：R285.5[医药卫生—中药学]