关键词: 右美托咪定, miR-490-3p/FOXO1轴, 糖尿病心肌缺血/再灌注, 心肌损伤, 炎性反应

Abstract: Objective To explore the effect and mechanism of dexmedetomidine (DEX) on myocardial injury and inflammation of rats with diabetic myocardial ischemia-reperfusion(MI/R). Methods The rats were divided into sham group, model grousp[The type 2 diabetes mellitus (T2DM) model was replicated by feeding high-fat and high-sugar combined with streptozotocin injection; MI/R injury model was replicated by coronary artery ligation], DEX group (T2DM model rats were injected with 10 μg/kg DEX through tail vein), antagomir NC group(T2DM model rats were injected with 10 μg/kg DEX and antagomir NC through tail vein), miR-490-3p antagomir group (T2DM model rats were injected with 10 μg/kg DEX and miR-490-3p antagomir via tail vein). RT-qPCR was applied to detect the expression of miR-490-3p and forkhead box O1(FOXO1) mRNA; Blood glucose meter was applied to measure fasting blood glucose (FBG) in rats; The level of fasting insulin(FINS), creatine kinase isoenzyme(CK-MB), lactate dehydrogenase(LDH) and inflammatory factors interleukin-1β(IL-1β) and tumor necrosis factor-α(TNF-α) was measured by ELISA; HE staining microscopy was applied to observe pathological damage of myocardial tissue; TTC staining microscopy was applied to determine the size of myocardial infarction; Dual luciferase assay was applied to verify the relationship between miR-490-3p and FOXO1; Western blot was applied to detect the expression of FOXO1 protein in myocardial tissue. Results Compared with the sham group, the FBG, FINS, CK-MB, LDH, IL-1β, TNF-α, myocardial infarction area, FOXO1 mRNA and protein expression in model group were all increased , while miR-490-3p expression decreased (P＜0.05); Compared with the model group, the FBG, FINS, CK-MB, LDH, IL-1β, TNF-α, myocardial infarction area, FOXO1 mRNA and protein expression in rats from DEX group decreased, the miR-490-3p expression increased(P＜0.05); Down regulation of miR-490-3p was able to significantly baffle the improvement of DEX on myocardial injury and inflammation in diabetes MI/R rats(P＜0.05); FOXO1 had a target-specific regulatory relationship with miR-490-3p. Conclusions DEX may inhibit inflammation and alleviate myocardial injury induced by MI/R in diabetic rat models by regulating the miR-490-3p/FOXO1 axis.

Key words: dexmetomidine, miR-490-3p/FOXO1 axis, myocardial ischemia/reperfusion in diabetes, myocardial injury, inflammation