Role of bilateral superior cervical sympathetic ganglion in myocardial ischemia-reperfusion injury in mice: relationship with NLRP3 inflammasomes / 中华麻醉学杂志

ABSTRACT

Objective:To evaluate the role of bilateral superior cervical sympathetic ganglia (SCG) in myocardial ischemia-reperfusion (I/R) injury in mice and the relationship with NOD-like receptor protein 3 (NLRP3) inflammasomes.Methods:Thirty-two healthy SPF male C57BL mice, aged 8-10 weeks, weighing 25-30 g, were divided into 4 groups ( n=8 each) by the random number table method: sham operation group (NS group), myocardial I/R group (NIR group), bilateral SCG excision group (SCGx group) and bilateral SCG excision + myocardial I/R group (SCGx+ IR group). The myocardial I/R injury model was prepared by ligating the anterior descending branch of the left coronary artery for 30 min followed by 24 h reperfusion in isoflurane-anesthetized mice. Bilateral superior cervical sympathectomy was performed at 3 days before reperfusion. Blood samples were collected from the inferior vena cava at 24 h of reperfusion for examination of pathological changes (by HE and WGA staining) and for measurement of serum creatine kinase isoenzymes (CK-MB) activity, cardiac troponin I (cTnI) concentration, norepinephrine (NE) concentration and lactic dehydrogenase (LDH) activity (by enzyme-linked immunosorbent assay), superoxide dismutase (SOD) activity (by colorimetric method), myocardial reactive oxygen species (ROS) level (by DHE method), myocardial infarct size(by TTC method), and expression of interleukin-1beta (IL-1β), IL-6, IL-10, tumor necrosis factor-alpha (TNF-α), NLRP3 mRNA (by quantitativepolymerase chain reaction ), and expression of tyrosine hydroxylase (TH), IL-1β, TNF-α, NLRP3, atrial natriuretic peptide (ANP)and brain natriuretic peptide (BNP) (by Western blot). Results:Compared with NS group, the NE concentration was significantly decreased, and TH expression was down-regulated in SCGx group, and the serum CK-MB activity, concentrations of cTnI and NE, LDH activity and myocardial ROS level were significantly increased, SOD activity was decreased, the expression of IL-1β, TNF-α, NLRP3, ANP and BNP was up-regulated, and the expression of IL-1β, IL-6, TNF-α and NLPR3 mRNA was up-regulated in NIR group ( P<0.05). Compared with SCGx group, the serum CK-MB activity, concentrations of cTnI and NE, LDH activity and myocardial ROS levels were significamtly increased, SOD activity was decreased, the expression of IL-1β, TNF-α, NLRP3, ANP and BNP was up-regulated, and the expression of IL-1β, IL-6, TNF-α and NLPR3 mRNA was up-regulated in SCGx+ NIR group ( P<0.05). Compared with NIR group, the serum CK-MB activity, cTnI concentration, LDH activity and myocardial ROS level were significantly decreased, SOD activity was increased, the expression of IL-1β, TNF-α, NLRP3, ANP and BNP was down-regulated, the expression of IL-1β, IL-6, TNF-α and NLPR3 mRNA was down-regulated, and myocardial infarct size was decreased in SCGx+ NIR group ( P<0.05). Conclusions:The mechanism by which bilateral SCG excision attenuates myocardial I/R injury is associated with decreased NLRP3 inflammatory inflammasome activation and inhibition of inflammatory responses in mice.