尿石素A预处理对肝缺血再灌注损伤大鼠模型的保护作用

米凯; 黄锐

doi:10.3969/j.issn.1001-5256.2020.08.021

尿石素A预处理对肝缺血再灌注损伤大鼠模型的保护作用

DOI: 10.3969/j.issn.1001-5256.2020.08.021

米凯,
黄锐

1. 核工业四一六医院(成都医学院第二附属医院)普外科
2. 四川省人民医院肝胆外科

基金项目:

国家自然科学基金项目(81302161)；四川省卫生与计划生育委员会课题(17PJ587)；

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中图分类号: R965
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出版历程
- 出版日期: 2020-08-20

Protective effect of urolithin A pretreatment in a rat model of hepatic ischemia-reperfusion injury

Mi Kai,
Huang Rui

Department of General Surgery, The Second Affiliated Hospital of Chengdu Medical College & Nuclear Industry 416 Hospital

Research funding:

摘要

摘要:
目的探讨尿石素A（Uro-A）对肝缺血再灌注损伤（HIRI）大鼠模型的保护作用。方法将40只SD大鼠随机分为假手术组、模型组、Uro-A低剂量组（1 mg/kg）和Uro-A高剂量组（3 mg/kg）,每组10只。造模前Uro-A低剂量和高剂量组每天灌胃药物1次,持续5 d。动物麻醉后造模,恢复血流后6 h检测血清中ALT、AST与乳酸脱氢酶（LDH）的含量,ELISA法检测肝组织中超氧化物歧化酶（SOD）、丙二醛（MDA）、过氧化氢酶（CAT）、IL-1β、IL-6和TNFα含量,观察肝脏病理损伤与肝细胞凋亡情况,Western Blot法检测肝脏中内质网分子伴侣葡萄糖调节蛋白78 （GRP78）、下游应激转录因子（CHOP）和凋亡蛋白家族（Caspase-12）的表达水平。计量资料多组间比较采用单因素方差分析,进一步两两比较采用LSD-t检验。结果 Uro-A高剂量组ALT、AST、LDH、MDA、CAT、IL-1β、IL-6、TNFα、CHOP、GRP78、Caspase-12水平及凋亡率均较模型组降低,SOD含量较模型组升高,差异均有统计学意义（P值均<0.05）。模型组...
- 肝疾病 /
- 再灌注损伤 /
- 尿石素A /
- 大鼠,Sprague-Dawley
Abstract:
Objective To investigate the protective effect of urolithin A(Uro-A) against hepatic ischemia-reperfusion injury(HIRI) in rats.Methods A total of 40 Sprague-Dawley rats were randomly divided into sham-operation group,model group,low-dose Uro-A(1 mg/kg) group,and high-dose Uro-A(3 mg/kg) group,with 10 rats in each group.Before modeling,the rats in the low-and high-dose Uro-A groups were given the drug by gavage once a day for 5 consecutive days.The model was established after anesthesia,and the serum levels of alanine aminotransferase(ALT),aspartate aminotransferase(AST),and lactate dehydrogenase(LDH) were measured at 6 hours after the recovery of blood flow.ELISA was used to measure the content of superoxide dismutase(SOD),malondialdehyde(MDA),catalase(CAT),interleukin-1β(IL-1β),interleukin-6(IL-6),and tumor necrosis factor-α(TNF-α) in the liver,and liver pathological injury and hepatocyte apoptosis were evaluated.Western blot was used to measure the expression of the endoplasmic reticulum chaperone glucose-regulated protein 78(GRP78),the downstream transcription factor CHOP,and the apoptosis protein caspase-12 in the liver.A one-way analysis of variance was used for comparison of continuous data between multiple groups,and the least significant difference t-test was used for further comparison between two groups.Results Compared with the model group,the high-dose Uro-A group had significantly lower levels of ALT,AST,LDH,MDA,CAT,IL-1β,IL-6,TNF-α,CHOP,GRP78,and caspase-12 and apoptosis rate and a significantly higher content of SOD(all P<0.05).The model group had severe damage of liver structure,with a positive rate of 90%,while the high-dose Uro-A group had intact liver structure without obvious tissue proliferation or inflammatory cell proliferation,with a negative rate of 80%.Compared with the high-dose Uro-A group,the low-dose Uro-A group had significant increases in the levels of ALT,AST,and LDH and apoptosis rate(all P<0.05).Conclusion Uro-A pretreatment can alleviate liver ischemia-reperfusion injury in rats and reduce oxidative damage and the release of inflammatory factors,possibly by inhibiting the endoplasmic reticulum stress pathways and reducing hepatocyte apoptosis.
- liver diseases /
- reperfusion injury /
- urolithin A /
- rats,Sprague-Dawley

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参考文献(17)

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