摘要Objective: To observe the protective effect of hesperidin on myocardial ischemia/ reperfusion injury in type 2 diabetes mellitus and its effect on SIRT1/Nrf2/HO-1 signaling pathway. Methods: 50 Sprague-Dawley (SD) rats were randomly assigned to the normal control group (NC), model group, ischemia-reperfusion group (IR), hesperidin group, SIRT1 inhibitor group and hesperidin plus SIRT1 inhibitor group. In addition to NC, the rats in the remaining groups were replicated by intraperitoneal of high-fat diet combined with injection of streptozotocin for type 2 diabetic rats. After then, the myocardial ischemia/reperfusion injury (MIRI) rat model was established by LAd for 30 minutes with 2 hours reperfusion. He staining was used to observe the pathological changes of myocardial tissue, and the levels of serum LDH, CK-MB and SOD, GSH and MDA in myocardial tissue were detected by kit methods, and the expression abundance of related proteins in 4-HNE and SIRT1/Nrf2/HO-1 signal pathway were detected by immunohistochemistry and Western blot; Results: Hesperidin could significantly inhibit cardiomyocyte necrosis and inflammatory cell infiltration, reduce LDH activity, CK-MB and MDA level, and increase SOD activity, GSH and 4-HNE level, the differences were statistically significant when compared with IR group (P<0.01). In addition, compared with the ischemia-reperfusion group, the expressions of SIRT1, Nrf2 and HO-1 proteins in hesperidin group were significantly up-regulated, the differences were statistically significant (P<0.01); Conclusion: Hesperidin inhibits oxidative stress by activating SIRT1/Nrf2/HO-1 signaling pathway, and play a protective effect of myocardial ischemia reperfusion injury in diabetic rats.