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异氟烷预处理通过激活Brg1/Nrf2/HO-1信号通路来保护糖尿病患者的肾脏免受缺血/再灌注损伤。

Isoflurane preconditioning protects against renal ischemia/reperfusion injury in diabetes via activation of the Brg1/Nrf2/HO-1 signaling pathway.

作者信息

Gong Daojing, Dong Ziqiang, Chen Xiaobo, Chen Hao, Lin Huihuang

机构信息

China Three Gorges University - The First Clinical College - Department of Urology - Yichang - China.

出版信息

Acta Cir Bras. 2024 Sep 30;39:e396124. doi: 10.1590/acb396124. eCollection 2024.

DOI:10.1590/acb396124
PMID:39356932
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11441133/
Abstract

PURPOSE

To examine whether isoflurane preconditioning (IsoP) has a protective effect against renal ischemia/reperfusion injury (I/RI) in diabetic conditions and to further clarify the underlying mechanisms.

METHODS

Control and streptozotocin-induced diabetic rats were randomly assigned to five groups, as follows: normal sham, normal I/R, diabetic sham, diabetic I/R, and diabetic I/R + isoflurane. Renal I/RI was induced by clamping renal pedicle for 45 min followed by reperfusion for 24 h. IsoP was achieved by exposing the rats to 2% isoflurane for 30 min before vascular occlusion. Kidneys and blood were collected after reperfusion for further analysis. Renal histology, blood urea nitrogen, serum creatinine, oxidative stress, inflammatory cytokines, and renal cell apoptosis were assessed. Furthermore, the expression of brahma related gene 1 (Brg1), nuclear factor-erythroid 2-related factor 2 (Nrf2), heme oxygenase-1 (HO-1), and nuclear factor-κB (NF-κB) were determined.

RESULTS

Compared with control, diabetic rats undergoing I/R presented more severe renal injury, oxidative stress, inflammatory reaction, and apoptosis with the impairment of Brg1/Nrf2/HO-1 signaling. All these alterations were significantly attenuated by pretreatment with isoflurane.

CONCLUSIONS

These findings suggest that isoflurane could alleviate renal I/RI in diabetes, possibly through improving Brg1/Nrf2/HO-1 signaling.

摘要

目的

研究异氟烷预处理（IsoP）对糖尿病状态下肾缺血/再灌注损伤（I/RI）是否具有保护作用，并进一步阐明其潜在机制。

方法

将对照大鼠和链脲佐菌素诱导的糖尿病大鼠随机分为五组，如下：正常假手术组、正常I/R组、糖尿病假手术组、糖尿病I/R组和糖尿病I/R + 异氟烷组。通过夹闭肾蒂45分钟，然后再灌注24小时诱导肾I/RI。在血管闭塞前，将大鼠暴露于2%异氟烷30分钟以实现IsoP。再灌注后收集肾脏和血液进行进一步分析。评估肾组织学、血尿素氮、血清肌酐、氧化应激、炎性细胞因子和肾细胞凋亡。此外，测定婆罗门相关基因1（Brg1）、核因子-红细胞2相关因子2（Nrf2）、血红素加氧酶-1（HO-1）和核因子-κB（NF-κB）的表达。

结果

与对照组相比，经历I/R的糖尿病大鼠表现出更严重的肾损伤、氧化应激、炎症反应和凋亡，同时Brg1/Nrf2/HO-1信号通路受损。异氟烷预处理可显著减轻所有这些改变。

结论

这些发现表明，异氟烷可能通过改善Brg1/Nrf2/HO-1信号通路减轻糖尿病中的肾I/RI。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6721/11441133/52c532c331d1/1678-2674-acb-39-e396124-gf04.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6721/11441133/35ec1b57cd3e/1678-2674-acb-39-e396124-gf01.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6721/11441133/c9b323035b04/1678-2674-acb-39-e396124-gf02.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6721/11441133/fdc29ac7b022/1678-2674-acb-39-e396124-gf03.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6721/11441133/52c532c331d1/1678-2674-acb-39-e396124-gf04.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6721/11441133/35ec1b57cd3e/1678-2674-acb-39-e396124-gf01.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6721/11441133/c9b323035b04/1678-2674-acb-39-e396124-gf02.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6721/11441133/fdc29ac7b022/1678-2674-acb-39-e396124-gf03.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6721/11441133/52c532c331d1/1678-2674-acb-39-e396124-gf04.jpg

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本文引用的文献

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Isoflurane suppresses lung ischemia-reperfusion injury by inactivating NF-κB and inhibiting cell apoptosis.异氟烷通过使核因子κB失活和抑制细胞凋亡来抑制肺缺血再灌注损伤。
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Diabetes aggravates renal ischemia and reperfusion injury in rats by exacerbating oxidative stress, inflammation, and apoptosis.
糖尿病通过加剧氧化应激、炎症和细胞凋亡加重大鼠肾缺血再灌注损伤。
Ren Fail. 2019 Nov;41(1):750-761. doi: 10.1080/0886022X.2019.1643737.
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Influence of Fat on Differential Receptor Interacting Serine/Threonine Protein Kinase 1 Activity Leading to Apoptotic Cell Death in Murine Liver Ischemia Reperfusion Injury Through Caspase 8.脂肪通过半胱天冬酶8对差异受体相互作用丝氨酸/苏氨酸蛋白激酶1活性的影响导致小鼠肝脏缺血再灌注损伤中的细胞凋亡性死亡。
Hepatol Commun. 2019 Apr 25;3(7):925-942. doi: 10.1002/hep4.1352. eCollection 2019 Jul.
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Comparison of Inflammatory Markers Between the Sevoflurane and Isoflurane Anesthesia in a Rat Model of Liver Ischemia/Reperfusion Injury.七氟醚与异氟醚麻醉在大鼠肝脏缺血/再灌注损伤模型中炎症标志物的比较
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