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Relationship between SIRT1 and NLRP3 inflammasomes during myocardial ischemia-reperfusion in diabetic rats / 中华麻醉学杂志
Chinese Journal of Anesthesiology ; (12): 421-424, 2020.
Article in Chinese | WPRIM | ID: wpr-869882
ABSTRACT

Objective:

To evaluate the relationship between silence information regulator 1 (SIRT1) and NOD-like receptor protein 3 (NLRP3) inflammasomes during myocardial ischemia-reperfusion (I/R) in diabetic rats.

Methods:

SPF-grade healthy male Sprague-Dawley rats, aged 6-8 weeks, weighing 200-220 g, were used in this study.Type 1 diabetes mellitus was induced by intraperitoneal 1% streptozotocin diluted in citrate buffer solution 60 mg/kg.The rats were continuously fed for 8 weeks after successful establishment of the model.Forty-two rats with type 1 diabetes mellitus were divided into 4 groups by a random number table

method:

diabetic sham operation group (DS group, n=6), diabetic myocardial I/R group (DIR group, n=12), diabetic myocardial I/R plus SIRT1 agonist SRT1720 group (DIR+ SR group, n=12) and diabetic myocardial I/R plus SIRT1 inhibitor EX-527 group (DIR+ EX group, n=12). Eighteen non-diabetic rats were divided into 2 groups by a random number table

method:

non-diabetic sham operation group (NS group, n=6) and non-diabetic myocardial I/R group (NIR group, n=12). The myocardial I/R model was established by ligation of the left anterior descending coronary artery for 30 min followed by 120-min reperfusion in anesthetized rats.Blood samples were collected from the carotid artery immediately after the end of reperfusion for determination of serum troponin I (cTnI), creatine kinase-MB (CK-MB) and lactate dehydrogenase (LDH) levels (by enzyme-linked immunosorbent assay). Then the rats were sacrificed, and myocardial tissues were obtained for determination of myocardial infarct size (by TTC method) and expression of SIRT1, NLRP3 and IL-1β (by Western blot) and for microscopic examination of pathological changes of myocardial tissues (by HE staining). The percentage of myocardial infarct size was calculated.

Results:

Compared with group NS, the serum levels of cTnI, CK-MB and LDH were significantly increased, the expression of SIRT1 in myocardial tissues was down-regulated, and the expression of NLRP3 and IL-1β was up-regulated in group NIR ( P<0.05). Compared with group DS, the serum levels of cTnI, CK-MB and LDH were significantly increased, the expression of SIRT1 in myocardial tissues was down-regulated, and the expression of NLRP3 and IL-1β was up-regulated in group DIR ( P<0.05). Compared with group NIR, the percentage of myocardial infarct size and serum levels of cTnI, CK-MB and LDH were significantly increased, the expression of SIRT1 in myocardial tissues was down-regulated, the expression of NLRP3 and IL-1β was up-regulated ( P<0.05), and the pathological changes were accentuated in group DIR.Compared with group DIR, the percentage of myocardial infarct size and serum levels of cTnI, CK-MB and LDH were significantly decreased, the expression of SIRT1 in myocardial tissues was up-regulated, the expression of NLRP3 and IL-1β was down-regulated ( P<0.05), and the pathological changes were significantly attenuated in group DIR+ SR, and the percentage of myocardial infarct size and serum levels of cTnI, CK-MB and LDH were significantly increased, the expression of SIRT1 in myocardial tissues was down-regulated, the expression of NLRP3 and IL-1β was up-regulated ( P<0.05), and the pathological changes were accentuated in group DIR+ EX.

Conclusion:

The up-regulated expression of SIRT1 can inhibit the activation of NLRP3 inflammasomes and produces endogenous protection during myocardial I/R in diabetic rats.
Full text: Available Index: WPRIM (Western Pacific) Language: Chinese Journal: Chinese Journal of Anesthesiology Year: 2020 Type: Article

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Full text: Available Index: WPRIM (Western Pacific) Language: Chinese Journal: Chinese Journal of Anesthesiology Year: 2020 Type: Article