Role of SIRT3-mediated CypD deacetylation in dexmedetomidine-induced reduction of renal ischemia-reperfusion injury in rats

Abstract

Objective To evaluate the role of silent information regulator 2 homolog 3 (SIRT3)-mediated cyclophilin D (CypD) deacetylation in dexmedetomidine-induced reduction of renal ischemia-reperfusion (I/R) injury in rats. Methods Thirty-two male Sprague-Dawley rats, aged 3-4 months, weighing 210-290 g, were randomly allocated into 4 groups (n=8 each) using a random number table: sham operation group (Sham group), I/R group, dexmedetomidine group (Dex group), and SIRT3 inhibitor Tenovin-6 group (Tenovin-6 group). Renal I/R was induced by occlusion of renal pedicles for 45 min followed by 48 h of reperfusion in rats anesthetized with phenobarbital sodium.Dexmedetomidine 50 μg/kg was injected intraperitoneally at 30 min prior to ischemia in Dex and Tenovin-6 groups.Tenovin-6 50 mg/kg was injected intraperitoneally at 1 h prior to dexmedetomidine administration in group Tenovin-6.At 48 h of reperfusion, renal tissues were obtained for examination of pathological changes (under light microscope), and for determination of cell apoptosis (by TUNEL), and CypD acetylation (by Western blot). The apoptosis index was calculated.The mitochondria were extracted for determination of mitochondrial permeability transition pore (mPTP) opening. Results Compared with group Sham, the apoptosis index, CypD acetylation and mPTP opening were significantly increased (P<0.05), and the pathological changes were aggravated in I/R, Dex and Tenovin-6 groups.Compared with group I/R, the apoptosis index, CypD acetylation and mPTP opening were significantly decreased (P<0.05), and the pathological changes were attenuated in group Dex.Compared with group Dex, the apoptosis index, CypD acetylation and mPTP opening were significantly increased (P<0.05), and the pathological changes were aggravated in group Tenovin-6. Conclusion SIRT3-mediated CypD deacetylation is involved in dexmedetomidine-induced reduction of renal I/R injury in rats. Key words: Dexmedetomidine; Reperfusion injury; Kidney; Sirtuins; Cyclophilins