Relationship between Rev-erbα and NLRP3 inflammasome during myocardial ischemia-reperfusion in diabetic rats / 中华麻醉学杂志

ABSTRACT

Objective:To evaluate the relationship between nuclear receptor subfamily 1, group D, member 1 (Rev-erbα) and NOD-like receptor protein 3 (NLRP3) inflammasome during myocardial ischemia-reperfusion (I/R) in diabetic rats.Methods:SPF-grade healthy male Sprague-Dawley rats, weighing 210-240 g, in which 1% streptozotocin 60 mg/kg was intraperitoneally injected to develop the model of type 1 diabetes mellitus.Eighteen non-diabetic rats were divided into 2 groups by the random number table method: non-diabetic sham operation group (NS group, n=6) and non-diabetic myocardial I/R group (NIR group, n=12). Thirty diabetic rats were divided into 3 groups by the random number table method: diabetic sham operation group (DS group, n=6), diabetic myocardial I/R group (DIR group, n=12), and diabetic myocardial I/R + Rev-erbα inhibitor SR8278 group (DIR+ SR group, n=12). Myocardial I/R model was developed by ligation of left anterior descending coronary artery for 30 min followed by reperfusion for 120 min.In DIR+ SR group, SR8278 2 mg/kg was injected via the femoral vein at 1 h before ischemia.At the end of reperfusion, blood samples from the right carotid artery were collected for determination of serum creatine kinase-MB (CK-MB), lactate dehydrogenase (LDH) and cardiac troponin I (cTnI) levels (by enzyme-linked immunosorbent assay). Then the rats were sacrificed, hearts were removed and myocardial tissues were obtained for determination of the percentage of myocardial infarct size (by TTC method) and expression of Rev-erbα, NLRP3 and IL-1β (by Western blot) and for microscopic examination of pathologic changes (by HE staining). Results:Compared with sham-operated rats, the serum concentrations of CK-MB, LDH and cTnI were significantly increased, the expression of Rev-erbα, NLRP3 and IL-1β in myocardial tissues was up-regulated ( P<0.05), and the pathological injury of myocardial tissues was obvious in myocardial I/R rats.Compared with NIR group, the percentage of myocardial infarct size and levels of serum CK-MB, LDH and cTnI were significantly increased, the expression of Rev-erb α, NLRP3 and IL-1β was up-regulated ( P<0.05), and the pathological injury of myocardial tissues was aggravated in DIR group.Compared with DIR group, the percentage of myocardial infarct size and serum CK-MB, LDH and cTnI levels were significantly decreased, the expression of Rev-erbα, NLRP3 and IL-1β was down-regulated ( P<0.05), and the pathological injury of myocardial tissues was reduced in DIR+ SR group. Conclusions:Rev-erbα can promote activation of NLRP3 inflammasome and is involved in the pathophysiological mechanism of myocardial I/R injury in diabetic rats.