Role and Potential Mechanism of Heme Oxygenase-1 in Intestinal Ischemia-Reperfusion Injury.
Role and Potential Mechanism of Heme Oxygenase-1 in Intestinal Ischemia-Reperfusion Injury.
复制标题
血红素加氧酶-1在肠缺血再灌注损伤中的作用及可能机制
DOI：
10.3390/antiox11030559
复制
发表时间：
2022-03-15
期刊：
影响因子：
--
通讯作者：
Itoh Y
中科院分区：
文献类型：
--
作者：
Katada K;Takagi T;Iida T;Ueda T;Mizushima K;Fukui A;Okayama T;Kamada K;Uchiyama K;Ishikawa T;Naito Y;Itoh Y
肠缺血再灌注（IR）损伤是一种复杂的、多因素的、高发病率和死亡率的病理生理疾病，给治疗带来了严重的困难，特别是在人类中。血红素加氧酶（HO）是参与血红素分解代谢的限速酶。HO-1（一种诱导型）通过抑制炎症和氧化来保护细胞。此外，核因子-红系2相关因子2 （Nrf2）正调控HO-1转录，而BTB和CNC同源物1 （Bach1）与Nrf2竞争并抑制其转录。我们探讨了HO-1在肠道IR损伤中的作用及其潜在机制。对野生型、bach1缺失型和nrf2缺失型小鼠进行肠缺血45min后再灌注4h，并给予一氧化碳（CO）释放分子(CORM)-3。在ir诱导的野生型小鼠肠道中观察到炎症标志物水平升高、核因子-κB （NF-κB）激活和形态学损伤。这些炎症变化在bach1缺陷小鼠或用CORM-3治疗的小鼠中显著减弱，而在nrf2缺陷小鼠中显著加剧。在ir诱导的bach1缺陷小鼠中，用HO-1抑制剂治疗逆转了这种衰减。Bach1缺乏和CORM-3处理导致NF-κB活化下调和粘附分子抑制。Bach1、Nrf2和CO是小肠IR损伤有价值的治疗靶点。
Intestinal ischemia-reperfusion (IR) injury is a complex, multifactorial, and pathophysiological condition with high morbidity and mortality, leading to serious difficulties in treatment, especially in humans. Heme oxygenase (HO) is the rate-limiting enzyme involved in heme catabolism. HO-1 (an inducible form) confers cytoprotection by inhibiting inflammation and oxidation. Furthermore, nuclear factor-erythroid 2-related factor 2 (Nrf2) positively regulates HO-1 transcription, whereas BTB and CNC homolog 1 (Bach1) competes with Nrf2 and represses its transcription. We investigated the role and potential mechanism of action of HO-1 in intestinal IR injury. Intestinal ischemia was induced for 45 min followed by 4 h of reperfusion in wild-type, Bach1-deficient, and Nrf2-deficient mice, and a carbon monoxide (CO)-releasing molecule (CORM)-3 was administered. An increase in inflammatory marker levels, nuclear factor-κB (NF-κB) activation, and morphological impairments were observed in the IR-induced intestines of wild-type mice. These inflammatory changes were significantly attenuated in Bach1-deficient mice or those treated with CORM-3, and significantly exacerbated in Nrf2-deficient mice. Treatment with an HO-1 inhibitor reversed this attenuation in IR-induced Bach1-deficient mice. Bach1 deficiency and treatment with CORM-3 resulted in the downregulation of NF-κB activation and suppression of adhesion molecules. Together, Bach1, Nrf2, and CO are valuable therapeutic targets for intestinal IR injury.
登录
查看更多内容
影响因子：
--
作者：
HERNANDEZ, LA;GRISHAM, MB;GRANGER, DN
通讯作者：
GRANGER, DN
影响因子：
2.5
作者：
Acosta, Stefan
通讯作者：
Acosta, Stefan
影响因子：
4.4
作者：
Sugimoto, Naohito;Rui, Tao;Kvietys, Peter R.
通讯作者：
Kvietys, Peter R.
影响因子：
7.4
作者：
Janssen-Heininger, YMW;Poynter, ME;Baeuerle, PA
通讯作者：
Baeuerle, PA
影响因子：
--
作者：
GRISHAM, MB;HERNANDEZ, LA;GRANGER, DN
通讯作者：
GRANGER, DN