[1]李泽信,王　霄,王　迎,等.漆黄素对小鼠缺血再灌注肝脏炎症性损伤的保护作用[J].新乡医学院学报,2020,37(11):1018-1022.[doi:10.7683/xxyxyxb.2020.11.004]
　LI Zexin,WANG Xiao,WANG Ying,et al.Protection of fisetin on inflammatory liver injury induced by hepatic ischemia-reperfusion in mice[J].Journal of Xinxiang Medical University,2020,37(11):1018-1022.[doi:10.7683/xxyxyxb.2020.11.004]
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漆黄素对小鼠缺血再灌注肝脏炎症性损伤的保护作用
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《新乡医学院学报》[ISSN:1004-7239/CN:41-1186/R]

卷:
37
期数:
2020年11
页码:
1018-1022
栏目:
基础研究
出版日期:
2020-11-05

文章信息/Info

Title:
Protection of fisetin on inflammatory liver injury induced by hepatic ischemia-reperfusion in mice
作者:
李泽信1; 王　霄2; 王　迎1; 李　建1; 李　荣3; 王建国1
（1.新乡医学院第一附属医院肝胆胰外科，河南　卫辉　453100；2.新乡医学院药学院，河南　新乡　453003；2.新乡医学院护理学院，河南　新乡　453003）
Author(s):
LI Zexin1; WANG Xiao2; WANG Ying1; LI Jian1; LI Rong3; WANG Jianguo1
(1.Department of General Surgery,the First Affiliated Hospital of Xinxiang Medical University,Weihui 453100,Henan Province,China;2.School of Pharmacy,Xinxiang Medical University,Xinxiang 453003,Henan Province,China;3.School of Nursing,Xinxiang Medical University,Xinxiang 453003,Henan Province,China)
关键词:
漆黄素; 缺血再灌注; 肝损伤; 核因子-κB; 炎性损伤
Keywords:
fisetin; ischemia-reperfusion; liver injury; nuclear factor-κB; inflammatory injury
分类号:
R619.9
DOI:
10.7683/xxyxyxb.2020.11.004
文献标志码:
A
摘要:
目的　探讨漆黄素对小鼠缺血再灌注肝脏炎症性损伤的保护作用及其机制。方法　将24只健康雄性C57BL/6小鼠随机分为假手术组、缺血再灌注组、低剂量漆黄素组和高剂量漆黄素组，每组6只。缺血再灌注组、低剂量漆黄素组和高剂量漆黄素组小鼠建立肝脏缺血再灌注模型，假手术组小鼠仅进行开关腹手术。制作模型前1 h，低剂量漆黄素组和高剂量漆黄素组小鼠分别腹腔注射漆黄素25、50 mg·kg-1；假手术组和缺血再灌注组小鼠腹腔注射等体积的二甲亚砜。缺血1 h后进行再灌注，再灌注6 h后以40 g·L-1水合氯醛腹腔注射（0.1 mL·10 g-1）麻醉小鼠，获取下腔静脉血液样本及肝脏。采用实时荧光定量聚合酶链反应法检测各组小鼠肝组织中核因子-κB （NF-κB）p65 mRNA表达，酶联免疫吸附试验检测各组小鼠肝组织中肿瘤坏死因子-α（TNF-α）、白细胞介素-6（IL-6）水平及血清中丙氨酸转氨酶（ALT）和天冬氨酸转氨酶（AST）水平；苏木精-伊红染色法观察各组小鼠肝组织病理学变化，并计算肝组织坏死面积所占百分比。结果　再灌注6 h后，假手术组、缺血再灌注组、低剂量漆黄素组和高剂量漆黄素组小鼠肝组织中NF-κB p65 mRNA相对表达量分别为1.012±0.224、6.893±0.716、3.287±0.402、1.238±0.311；缺血再灌注组小鼠肝组织中NF-κB p65 mRNA相对表达量显著高于假手术组（P<0.05），低剂量漆黄素组小鼠肝组织中NF-κB p65 mRNA相对表达量显著低于缺血再灌注组（P<0.05），高剂量漆黄素组小鼠肝组织中NF-κB p65 mRNA相对表达量显著低于低剂量漆黄素组（P<0.05）。再灌注6 h后，缺血再灌注组小鼠肝组织中TNF-α、IL-6水平和血清ALT、AST水平显著高于假手术组（P<0.05），低剂量漆黄素组小鼠肝组织中TNF-α、IL-6水平和血清ALT、AST水平显著低于缺血再灌注组（P<0.05），高剂量漆黄素组小鼠肝组织中TNF-α、IL-6水平和血清ALT、AST水平显著低于低剂量漆黄素组（P<0.05）。假手术组、缺血再灌注组、低剂量漆黄素组和高剂量漆黄素组小鼠肝组织坏死面积分别为（0.698±0.127）%、（51.650±3.410）%、（28.847±2.069）%、（19.877±1.213）%；缺血再灌注组小鼠肝组织坏死面积显著大于假手术组（P<0.05），低剂量漆黄素组小鼠肝组织坏死面积显著小于缺血再灌注组（P<0.05），高剂量漆黄素组小鼠肝组织坏死面积显著小于低剂量漆黄素组（P<0.05）。结论　漆黄素预处理可以显著减轻小鼠缺血再灌注肝脏损伤，其机制可能与抑制NF-κB炎症通路激活有关。
Abstract:
Objective　To investigate the protection and mechanism of fisetin on the inflammatory liver injury induced by hepatic ischemia-reperfusion in mice.Methods　Twenty-four C57BL/6 male mice were randomly divided into sham operation group,ischemia-reperfusion group,low-dose fisetin group and high-dose fisetin group,with six mice in each group.The hepatic ischemia-reperfusion models of mice were established in the ischemia-reperfusion group,low-dose fisetin group and high-dose fisetin group,while the mice in the sham operation group were only performed with abdominal operation.The mice in the low-dose fisetin group and high-dose fisetin group were respectively given fisetin (25,50 mg·kg-1) by intraperitoneal injection at one hour before modeling;while the mice in the sham operation group and ischemia-reperfusion group were given the same volume of dimethyl sulfoxide by intraperitoneal injection.After one hour of ischemia and six hours of reperfusion,the mice were anesthetized with 40 g·L-1 chloral hydrate by intraperitoneal injection (0.1 mL·10 g-1),and the blood samples of inferior vena cava and hepatic tissues were obtained.The expression of nuclear factor-κB (NF-κB) p65 mRNA in hepatic tissues of mice in each group was detected by real-time fluorescence quantitative polymerase chain reaction.The levels of tumor necrosis factor α (TNF-α) and interleukin-6 (IL-6) in hepatic tissues of mice were measured by enzyme-linked immunosorben assay,while the levels of serum alanine transarninase (ALT) and aspartate transaminase (AST) were determined by enzyme-linked immunosorben assay.The pathological changes of hepatic tissues were observed by hematine-eosin staining,and the percentage of necrotic area of hepatic tissues was calculated.Results　After six hours of reperfusion,the relative expression of NF-κB p65 mRNA in hepatic tissues of mice in the sham operation group,ischemia-reperfusion group,low-dose fisetin group and high-dose fisetin group was 1.012±0.224,6.893±0.716,3.287±0.402 and 1.238±0.311,respectively.The relative expression of NF-κB p65 mRNA in hepatic tissues of mice in the ischemia-reperfusion group was significantly higher than that in the sham operation group(P<0.05).The relative expression of NF-κB p65 mRNA in hepatic tissues of mice in the low-dose fisetin group was significantly lower than that in the ischemia-reperfusion group(P<0.05).The relative expression of NF-κB p65 mRNA in hepatic tissues of mice in the high-dose fisetin group was significantly lower than that in the low-dose fisetin group(P<0.05).After six hours of reperfusion,the levels of TNF-α and IL-6 in hepatic tissues and the levels of serum ALT and AST in the ischemia-reperfusion group were significantly higher than those in the sham operation group (P<0.05),the levels of TNF-α and IL-6 in hepatic tissues and the levels of serum ALT and AST in the low-dose fisetin group were significantly lower than those in the ischemia-reperfusion group (P<0.05),the levels of TNF-α and IL-6 in hepatic tissues and the levels of serum ALT and AST in the high-dose fisetin group were significantly lower than those in the low-dose fisetin group (P<0.05).The necrotic area of hepatic tissues in the sham operation group,ischemia-reperfusion group,low-dose fisetin group and high-dose fisetin group was (0.698±0.127)%,(51.65±3.41)%,(28.847±2.069)% and (19.877±1.213)%,respectively.The necrotic area of hepatic tissues in the ischemia-reperfusion group was significantly larger than that in the sham operation group(P<0.05).The necrotic area of hepatic tissues in the low-dose fisetin group was significantly smaller than that in the ischemia-reperfusion group(P<0.05).The necrotic area of hepatic tissues in the high-dose fisetin group was significantly smaller than that in the low-dose fisetin group(P<0.05).Conclusion　Fisetin pretreatment can significantly reduce the liver injury induced by ischemia-reperfusion in mice,and the mechanism may be related to inhibiting the activation of NF-κB inflammatory pathway.

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更新日期/Last Update: 2020-11-05