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Role of NRF2 in myocardial ischemia-reperfusion injury in diabetic rats: relationship with ferroptosis / 中华麻醉学杂志
Article in Chinese | WPRIM | ID: wpr-911199
Responsible library: WPRO
ABSTRACT

Objective:

To evaluate the role of nuclear factor E2-related factor 2 (NRF2) in myocardial ischemia-reperfusion (I/R) injury and the relationship with ferroptosis in diabetic rats.

Methods:

Forty-eight SPF healthy adult male Sprague-Dawley rats, aged 6-8 weeks, weighing 200-220 g, were divided into 5 groups by a random number table

method:

sham operation group (group S, n=6), myocardial I/R group (group NIR, n=12), diabetes mellitus+ sham operation group (group DS, n=6), diabetes mellitus+ myocardial I/R group (group DIR, n=12) and diabetes mellitus+ myocardial I/R+ NRF2 agonist sulforaphane group (group DIR+ SFN, n=12). Type 1 diabetes mellitus was induced by intraperitoneal injection of 1% streptozotocin-citrate buffer 60 mg/kg.Sulforaphane 500 μg·kg -1·d -1 was injected intraperitoneally before ischemia for 3 consecutive days in group DIR+ SFN.At the 8th week after establishing the model, myocardial I/R was produced by occlusion of the anterior descending branch of the left coronary artery for 30 min followed by reperfusion.At 2 h of reperfusion, the left ventricular systolic pressure (LVSP), HR, and the maximum rate of increase and decrease of left ventricular systolic pressure (±dp/dt max) were recorded.Blood samples were taken from the carotid artery and the animals were then sacrificed for determination of concentration of cardiac troponin I (cTnI) in serum (using enzyme-linked immunosorbent assay), myocardial Fe 2+ and malondialdehyde (MDA) contents, superoxide dismutase (SOD) activity (by colorimetry) and myocardial infarct size (using TTC) and for determination of expression of NRF2, ferroportin1 (FPN1) and acyl-CoA synthetase long-chain family member 4 (ACSL4) (by Western blot), and the pathological changes of lung tissues were observed by hematoxylin-eosin staining.

Results:

Compared with group S, LVSP, HR, and ±dp/dt max were significantly decreased, serum cTnI concentration and myocardial Fe 2+ and MDA contents were increased, SOD activity was decreased, expression of ACSL4 was up-regulated and expression of NRF2 and FPN1 was down-regulated in group NIR ( P<0.05). Compared with group DS, LVSP, HR, and ±dp/dt max were significantly decreased, serum cTnI concentration and myocardial Fe 2+ and MDA contents were increased, SOD activity was decreased, expression of ACSL4 was up-regulated and expression of NRF2 and FPN1 was down-regulated in group DIR ( P<0.05). Compared with group NIR, LVSP, HR, and ±dp/dt max were significantly decreased, serum cTnI concentration and myocardial Fe 2+ and MDA contents were increased, SOD activity was decreased, myocardial infarct size was increased, expression of ACSL4 was up-regulated and expression of NRF2 and FPN1 was down-regulated in group DIR ( P<0.05). Compared with group DIR, LVSP, HR, and ±dp/dt max were significantly increased, serum cTnI concentration and myocardial Fe 2+ and MDA contents were decreased, SOD activity was increased, myocardial infarct size was decreased, expression of ACSL4 was down-regulated and expression of NRF2 and FPN1 was up-regulated in group DIR+ SFN ( P<0.05).

Conclusion:

NRF2 is involved in the process of myocardial I/R injury, which is related to promoting ferroptosis in diabetic rats

Full text: Available Index: WPRIM (Western Pacific) Language: Chinese Journal: Chinese Journal of Anesthesiology Year: 2021 Type: Article

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Full text: Available Index: WPRIM (Western Pacific) Language: Chinese Journal: Chinese Journal of Anesthesiology Year: 2021 Type: Article