The effect of crocetin on Akt/GSK-3β/eNOS signaling pathway in myocardial ischemia-reperfusion injury of isolated rat hearts / 天津医药

ABSTRACT

Objective To study the protective effects of crocetin on myocardial ischemia-reperfusion injury, and their correlation with the signaling pathway of serine/threonine protein kinase (Akt)/glycogen synthase kinase (GSK)-3β/nitric ox?ide synthase (eNOS). Methods Forty healthy SD rats were divided into normal group (N), ischemia reperfusion group (IR) and 5, 10 and 15 mg/L of crocetin groups (CRO1, CRO2 and CRO3) by random number table method. The values of heart rate (HR), coronary flow (CF) and left ventricular pressure measurement (LVDP, LV+dp/dtmax, LV-dp/dtmax) 30 minutes after reperfusion were compared between five groups. TTC staining was used to detect the infarct volume. Spectrophotometric method was used to determinate the expression of lactate dehydrogenase (LDH) and creatine kinase (CK-MB). The levels of Akt, the phosphorylation of Akt (p-Akt), GSK-3β, phosphorylation of GSK-3β(p-GSK-3β), eNOS and phosphorylation of eNOS (p-NOS) were detected by Western blot assay. Results The HR, CF, LVDP, LV+dp/dtmax and LV-dp/dtmax were significantly lower 30 min after reperfusion in IR group than those of N group and crocetin groups (P<0.05). The myocardial infarction area was bigger in IR group than that of crocetin groups. The expression levels of LDH and CK-MB were signifi?cantly higher in IR group than those of N group and crocetin groups (P<0.05). The reperfusion index was higher in CRO3 group than that of CRO1 group. The infarction area, LDH and CK-MB expressions were significantly decreased in CRO3 group than those of CRO1 group (P<0.05). There were no significant differences in expressions of Akt, GSK-3βand eNOS between IR group, N group and crocetin groups. But p-Akt, p-GSK-3βand p-NOS were significantly decreased in IR group than those of N group and crocetin groups. The p-Akt, p-GSK-3βand p-NOS were significantly increased in CRO3 group than those of CRO1 group (P<0.05).Conclusion Crocetin has protective effects on myocrdial ischemia reperfusion injury in rats, which may be involved in the enhancing the phosphorylation of signalling pathway of Akt/GSK-3β/eNOS.