Objective To investigate the role of N-acetylglucosamine transferase V(GnT-V)in myocardial injury of diabetic mice and its underlying mechanism.Methods Thirty 6-8-week-old male C57BL/6 mice were randomly divided into control group(Ctrl group),diabetes mellitus group(DM group),and diabetes mellitus+AAV-shGnT-V group(DM+shGnT-V group),with 10 mice in each group.Echocardiography was used to detect the cardiac function and the left ventricular weight,HE staining was used to observe the pathological changes of myocardial tissues,and real-time quantitative PCR was used to detect the expressions of atrial natriuretic peptide(ANP)and B-type natriuretic peptide(BNP)in myocardial tissues.Western blot was used to detect GnT-V and TAK1 protein expressions in myocardial tissues.Primary cardiomyocytes were divided into normal glucose group(NG group),high glucose group(HG group),high glucose+Ad-shGnT-V group(HG+Ad-shGnT-V group)and high glucose+Ad-shGnT-V+Ad-TAK1 group(HG+Ad-shGnT-V+Ad-TAK1 group).Western blot was used to detect GnT-V and TAK1 protein expressions,and immunofluorescence was used to detect the level of α-actinin expression.Results Compared with Ctrl group,the cardiac systolic function was decreased(P＜0.001),the left ventricular mass was significantly increased(P＜0.001),the diameters of cardiomyocytes were increased(P＜0.001),and the expressions of GnT-V,TAK1 and the mRNA levels of ANP and BNP were significantly elevated in DM group(P＜0.05).Compared with DM group,the cardiac function was significantly improved in DM+shGnT-V group(P＜0.01),the left ventricular mass was decreased(P＜0.01),the symptoms of cardiac hypertrophy were significantly reduced(P＜0.001),and the expressions of GnT-V,TAK1,ANP and BNP were significantly reduced(P＜0.05).Compared with NG group,α-actinin immunofluorescence intensity was significantly enhanced in HG group,and GnT-V,TAK1 expressions were significantly increased(P＜0.05).Compared with HG group,GnT-V and TAK1 expressions were significantly reduced in HG+Ad-shGnT-V group(P＜0.05),and α-actinin immunofluo-rescence intensity was significantly decreased.Compared with HG+Ad-shGnT-V group,GnT-V expression showed no significant change in HG+Ad-shGnT-V+Ad-TAK1 group,TAK1 expression was significantly increased(P＜0.05),and α-actinin immunofluo-rescence intensity was also enhanced.Conclusion GnT-V may modulate the myocardial injury in diabetic mice through the activation of TAK1.
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