摘要
目的:探讨瑞香素对小鼠肝脏缺血再灌注损伤(IRI)的保护作用及机制。方法:构建小鼠70%肝脏IRI模型,将小鼠随机分为假手术组(Sham组)、瑞香素组(Dap组)、缺血再灌注组(IRI组)、缺血再灌注+瑞香素组(IRI+Dap组),每组8只。Sham组和IRI组小鼠腹腔注射0.9%氯化钠溶液,Dap组和IRI+Dap组小鼠肝脏缺血前1 h腹腔注射Dap(1.5 mg/kg)。IRI术后12 h处死小鼠收集标本,检测血清转氨酶及炎症因子的表达水平,取肝组织行苏木紫-伊红(HE)染色观察肝组织病理损伤,通过免疫荧光检测肝组织炎症因子的表达,通过ELISA检测肝组织氧化应激相关因子表达,通过蛋白印迹实验检测肝组织NRF2/HO-1通路相关蛋白的表达。结果:和IRI组小鼠相比,IRI+Dap组小鼠肝脏IRI 12 h后,血清中ALT、AST、TNFα、CCL2的表达显著降低,肝组织坏死面积显著减小,肝组织中CD11b、Ly6g阳性炎症细胞浸润属相显著减少,肝组织中MDA水平显著降低、SOD、GSH水平显著升高,同时肝组织中Keap1表达显著降低、HO-1、p-NRF2表达显著升高。结论:瑞香素能够显著抑制小鼠肝脏IRI后的炎症和氧化应激。瑞香素对肝脏IRI的保护作用可能是通过激活Keap1-NRF2通路实现。
Objective:To investigate the protective effect and mechanism of daphnetin on hepatic ischemia-reperfusion injury(IRI)in mice.Methods:The 70%liver IRI model of mice was established.The mice were randomly divided into sham operation group(sham group),daphnetin group(DAP group),ischemia-reperfusion group(IRI group),ischemia-reperfusion+daphnetin group(IRI+DAP group),with 8 mice in each group.Mice in sham group and IRI group were intraperitoneally injected with 0.9%sodium chloride solution.Mice in DAP group and IRI+DAP group were intraperitoneally injected with DAP(1.5 mg/kg)one hour before liver ischemia.At 12 hours after IRI,the mice were killed to collect samples,and the expression levels of serum transaminase and inflammatory factors were detected.The liver tissue was stained with hematoxylin eosin(HE)to observe the pathological damage.The expression of inflammatory factors in liver tissue was detected by immunofluorescence,and the expression of oxidative stress related factors in liver tissue was detected by ELISA.The expression of Keap1/Nrf2 pathway related proteins in liver tissue was detected by Western blot.Results:Compared with the IRI group,the expression of ALT,AST,TNFαand CCL2 in the serum of the mice in the IRI+Dap group were significantly reduced after 12 h of liver IRI,the area of liver tissue necrosis was significantly reduced,and the CD11b and Ly6g positive inflammatory cells in the liver tissue were significantly reduced.The level of MDA in liver tissue was significantly reduced,and the levels of SOD and GSH were significantly increased.At the same time,the expression of Keap1 in liver tissue was significantly reduced,and the expression of HO-1 and p-NRF2 was significantly increased.Conclusion:Daphnetin can significantly inhibit inflammation and oxidative stress in mice liver after IRI.The protective effect of daphnetin on liver IRI may be achieved by activating keap1-NRF2 pathway.
作者
陈三洋
余起文
宋耀东
程波
刘艳娜
崔宗朝
CHEN San-yang;YU Qi-wen;SONG Yao-dong;CHENG Bo;LIU Yan-na;CUI Zong-chao(Department of Emergence,the First Affiliated Hospital of Zhengzhou University,Zhengzhou 450052,China)
出处
《中国现代普通外科进展》
CAS
2023年第3期175-178,183,共5页
Chinese Journal of Current Advances in General Surgery
基金
河南省高等学校重点科研项目(21A320050)。
关键词
肝脏缺血再灌注损伤
瑞香素
炎症
氧化应激
NRF2
小鼠
Hepatic ischemia-reperfusion injury
Daphnetin
Inflammation
Oxidative stress
NRF2
Mouse
