Role of SphK1/S1P signaling pathway in adiponectin-induced restoration of attenuation of myocardial ischemia-reperfusion injury by sevoflurane postconditioning in diabetic rats

Xianliang XING; Na ZHENG; Jing ZHANG; Yanhui HU; Qin LIU

ABSTRACT

Objective:

To evaluate the role of SphK1/S1P signaling pathway in adiponectin-induced restoration of attenuation of myocardial ischemia-reperfusion (I/R) injury by sevoflurane postconditioning in diabetic rats.

Methods:

Healthy clean-grade male Sprague-Dawley rats, aged 8-10 weeks, weighing 250-300 g, in which diabetes mellitus was induced by combination of high-fat and high-sucrose diet and intraperitoneal injection of 1% streptozotoein in citric acid buffer 40 mg/kg, were studied.Ninety rats with diabetes mellitus were divided into 6 groups ( n=15 each) using a random number table

method:

sham operation group (group Sham), group I/R, sevoflurane postconditioning group (group S), adiponectin preconditioning group (group A), adiponectin preconditioning+ sevoflurane postconditioning group (group AS) and adiponectin preconditioning+ K6PC-5 (a specific SphK1 activator)+ sevoflurane postconditioning group (group AKS). Myocardial I/R was induced by 30 min occlusion of anterior descending branch of left coronary artery followed by 120 min reperfusion.At 15 min before ischemia, recombinant adiponectin 5.0 μg/g was injected intraperitoneally in A, AS and AKS groups, and K6PC-5 1 μg/g was injected via the tail vein in group AKS.In S, AS and AKS groups, 2.5% sevoflurane was inhaled for 5 min starting from the onset of reperfusion.Blood samples from the internal jugular vein were collected at the end of reperfusion for determination of serum cardiac troponin I (cTnI) concentration (by enzyme-linked immunosorbent assay), percentage of myocardial infarct volume (by TTC staining) and expression of SphK1, S1P and phosphorylated NF-κB p65 (p-NF-κB p65) in myocardial tissues (by Western blot).

Results:

Compared with group Sham, the serum cTnI concentration and percentage of myocardial infarct volume were significantly increased, and expression of SphK1, S1P and p-NF-κB p65 in myocardial tissues was up-regulated in group I/R ( P<0.05). Compared with group I/R, no significant change was found in each parameter in group S ( P>0.05), and the serum cTnI concentration and percentage of myocardial infarct volume were significantly decreased, and expression of SphK1, S1P and p-NF-κB p65 in myocardial tissues was down-regulated in group A ( P<0.05). Compared with group S, the serum cTnI concentration and percentage of myocardial infarct volume were significantly decreased, and expression of SphK1, S1P and p-NF-κB p65 in myocardial tissues was down-regulated in group AS ( P<0.05). Compared with group AS, the serum cTnI concentration and percentage of myocardial infarct volume were significantly increased, and expression of SphK1, S1P and p-NF-κB p65 in myocardial tissues was up-regulated in group AKS ( P<0.05).

Conclusion:

SphK1/S1P signaling pathway is involved in adiponectin-induced restoration of attenuation of myocardial I/R injury by sevoflurane postconditioning in diabetic rats.