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缺血后处理对脂肪变性大鼠肝脏缺血再灌注损伤的保护作用。

Protective effect of ischemic postconditioning on ischemia reperfusion injury in steatotic rat livers.

作者信息

He Jia-Xing, Wang Ke, Zhou Shuai, Fang Xiong-Chao, Zhang Bo, Yang Ying, Wang Nan

机构信息

Department of General Surgery, Tangdu Hospital, The Air Force Medical University, Xi'an, China.

出版信息

Ann Transl Med. 2021 Aug;9(16):1295. doi: 10.21037/atm-21-2275.

DOI:10.21037/atm-21-2275
PMID:34532432
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8422122/
Abstract

BACKGROUND

Hepatic steatosis creates a significant risk of liver resection and transplantation and is extremely susceptible to ischemia/reperfusion (I/R) injury. Ischemic postconditioning (IPostC) has been shown to attenuate I/R injury in normal livers; however, its role in steatotic livers remains unknown. The current study sought to explore whether IPostC could attenuate normothermic I/R injury in rats with steatotic livers and to investigate potential protective measures.

METHODS

Hepatic steatosis was triggered in Wistar rats fed high-fat diets. The role of IPostC was detected in normal and steatotic livers with 30 min of ischemia and 6 h of reperfusion. Blood and liver tissues were collected to assess hepatocyte damage, lipid peroxidation, inflammatory factors, neutrophil accumulation, and adenosine triphosphate (ATP) content.

RESULTS

Compared to normal livers, steatotic livers were more susceptible to I/R damage, as evidenced by incremental concentrations of liver enzymes in the blood and more severe pathological changes in the liver. Hepatic I/R injury was significantly reduced by IPostC in both normal and steatotic livers. We further found that endogenous protective measures moderated lipid peroxidation, inflammatory cytokine expression and neutrophil accumulation, and reduced follow-up hepatic injury. The ATP content of steatotic livers was also significantly lower than that of Normal livers before and after I/R injury. IPostC greatly preserved the ATP content of normal and steatotic livers with I/R injury.

CONCLUSIONS

IPostC appears to provide important protection against hepatic I/R injury in normal and steatotic livers under normothermic conditions. These data have important clinical implications for liver surgery and transplantation.

摘要

背景

肝脂肪变性会给肝切除和肝移植带来重大风险,且极易受到缺血/再灌注(I/R)损伤。缺血后处理(IPostC)已被证明可减轻正常肝脏的I/R损伤;然而,其在脂肪变性肝脏中的作用仍不清楚。本研究旨在探讨IPostC是否能减轻脂肪变性大鼠肝脏的常温I/R损伤,并研究潜在的保护措施。

方法

给Wistar大鼠喂食高脂饮食以引发肝脂肪变性。在正常和脂肪变性肝脏中检测IPostC在缺血30分钟和再灌注6小时后的作用。收集血液和肝脏组织以评估肝细胞损伤、脂质过氧化、炎症因子、中性粒细胞聚集和三磷酸腺苷(ATP)含量。

结果

与正常肝脏相比,脂肪变性肝脏对I/R损伤更敏感,血液中肝酶浓度升高以及肝脏更严重的病理变化证明了这一点。IPostC在正常和脂肪变性肝脏中均显著减轻了肝I/R损伤。我们进一步发现内源性保护措施减轻了脂质过氧化、炎症细胞因子表达和中性粒细胞聚集,并减少了后续肝损伤。脂肪变性肝脏在I/R损伤前后的ATP含量也显著低于正常肝脏。IPostC极大地保留了I/R损伤的正常和脂肪变性肝脏的ATP含量。

结论

IPostC似乎在常温条件下为正常和脂肪变性肝脏的肝I/R损伤提供了重要保护。这些数据对肝脏手术和移植具有重要的临床意义。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b597/8422122/c6d93db18711/atm-09-16-1295-f8.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b597/8422122/31bfc351e1c3/atm-09-16-1295-f1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b597/8422122/0f6caa605515/atm-09-16-1295-f2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b597/8422122/de2c527df624/atm-09-16-1295-f3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b597/8422122/a649ff7a5a3f/atm-09-16-1295-f4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b597/8422122/b86b640769b4/atm-09-16-1295-f5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b597/8422122/891ee19b0b34/atm-09-16-1295-f6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b597/8422122/b289aaa94b42/atm-09-16-1295-f7.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b597/8422122/c6d93db18711/atm-09-16-1295-f8.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b597/8422122/31bfc351e1c3/atm-09-16-1295-f1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b597/8422122/0f6caa605515/atm-09-16-1295-f2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b597/8422122/de2c527df624/atm-09-16-1295-f3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b597/8422122/a649ff7a5a3f/atm-09-16-1295-f4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b597/8422122/b86b640769b4/atm-09-16-1295-f5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b597/8422122/891ee19b0b34/atm-09-16-1295-f6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b597/8422122/b289aaa94b42/atm-09-16-1295-f7.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b597/8422122/c6d93db18711/atm-09-16-1295-f8.jpg

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Effect of remote ischemic preconditioning on kidney injury among high-risk patients undergoing cardiac surgery: a randomized clinical trial.远程缺血预处理对高危心脏手术患者肾损伤的影响:一项随机临床试验。
JAMA. 2015 Jun 2;313(21):2133-41. doi: 10.1001/jama.2015.4189.
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Acute atorvastatin is hepatoprotective against ischaemia-reperfusion injury in mice by modulating eNOS and microparticle formation.
急性阿托伐他汀通过调节内皮型一氧化氮合酶(eNOS)和微粒形成对小鼠缺血再灌注损伤具有肝保护作用。
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Ischemic preconditioning protects against liver ischemia/reperfusion injury via heme oxygenase-1-mediated autophagy.缺血预处理通过血红素加氧酶-1介导的自噬保护肝脏免受缺血/再灌注损伤。
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The effect of brain death in rat steatotic and non-steatotic liver transplantation with previous ischemic preconditioning.缺血预处理对脑死亡大鼠供肝脂肪变性和非脂肪变性肝移植的影响。
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