Relationship between mechanism of SIRT1-mediated mitophagy in myocardium and Mfn2 in diabetic rats / 中华麻醉学杂志

ABSTRACT

Objective To evaluate the relationship between the mechanism of silent information regulator factor 2-related enzyme 1 (SIRT1)-mediated mitophagy in the myocardium and mitofusin 2 (Mfn2) in diabetic rats.Methods Twenty-four SPF healthy adult male Sprague-Dawley rats,weighing 210-220 g,were allocated into 3 groups (n =8 each) using a random number tablecontrol group (group C),diabetes mellitus group (group DM) and diabetes mellitus plus SIRT1 activator SRT1720 group (group DM+SRT).Diabetes mellitus was induced by intraperitoneal 1％ streptozotocin 60 mg/kg and confirmed by blood glucose ≥ 16.7 mmol/L 3 days later.SRT1720 1 mg/kg was injected via the caudal vein for 7 consecutive days in group DM+SRT.The ultrasonic method was used to measure the parameters of heart function including left ventricular end-diastolic volume (LVEDV),left ventricular end-systolic volume (LVESV),left ventricular ejection fraction (LVEF),heart rate (HR),E wave velocity (E),A wave velocity (A) and E/A ratio.Myocardial specimens were obtained for determination of the interaction between SIRT1 and Mfn2 and acetylation of Mfn2 (by co-immuno-precipitation) and expression of SIRT1,Mfn2,microtubule-associated protein 1 light chain 3 Ⅱ (LC3 Ⅱ),LC3 Ⅰ,Beclin1 and P62 (by Western blot).The ratio LC3 Ⅱ to LC3 Ⅰ (LC3 Ⅱ / Ⅰ ratio) was calculated.Results Compared with group C,LVEDV,LVEF,HR,E and E/A ratio were significantly decreased,A was increased,LC3 Ⅱ / Ⅰ ratio was decreased,the expression of Beclin1,SIRT1 and Mfn2 was down-regulated,the expression of P62 was up-regulated,and the interaction between SIRT1 and Mfn2 was decreased in group DM (P＜0.05).Compared with group DM,LVEDV,LVEF,E and E/A ratio were significantly increased,A was decreased,LC3 Ⅱ / Ⅰ ratio was increased,the expression of Beclin1 and SIRT1 was up-regulated,the expression of P62 was down-regulated,the interaction between SIRT1 and Mfn2 was increased,and the acetylation of Mfn2 was decreased in group DM+SRT (P＜0.05).Conclusion The mechanism by which SIRT1 mediates mitophagy in the myocardium is related to SIRT1-induced deacetylation of Mfn2 in diabetic rats.