Effects of glucagon-like peptide-1 on the expression of nicotinamide adenine dinucleotide phosphate oxidase subunits in the heart of type 1 diabetic rats

Abstract

Objective To explore the effect of glucagon-like peptide-1 on the expression of nicotinamide adenine dinucleotide phosphate (NADPH) oxidase subunits p22phox and Nox4 in the heart tissue of type 1 diabetic rats. Methods Forty-two male Sprague-Dawley(SD) rats were randomly divided into normal control group(group A, n=7) and diabetic model group(n=35) with the random number table. Type 1 diabetic model was established by intraperitoneal injection of streptozotocin. Twenty-nine successfully-induced diabetic rats were randomly divided into diabetic (group DM, n=10), diabetic treated with low-dose of GLP-1 (group DL, n=10) and diabetic treated with high-dose of GLP-1(group DH, n=9) with the random number table method. The rats in group DL were given exenatide in dose of 1 μg/kg twice daily by subcutaneous injection. The rats in group DH were given exenatide in dose of 5 μg/kg twice daily by subcutaneous injection. All rats were sacrificed after exenatide treatment for eight weeks. The mRNA expression of myocardial p22phox and Nox4 in the rats of four groups was detected by real-time fluorescence quantitative polymerase chain reaction(PCR), and the protein expression of myocardial copper-zinc-superoxide dismutase (Cu-Zn-SOD) was detected by immunohistochemical staining. Statistical analysis among groups was performed by using one way ANOVA. Results Compared with group NC, the mRNA expression of myocardial p22phox and Nox4 and the myocardial Cu-Zn-SOD protein expression increased significantly in group DM(t=5.77, 5.36, 59.91, all P 0.05). Conclusions GLP-1 can dose-dependently down-regulate the over-expression of myocardial Nox4 and p22phox mRNA, and dose-independently up-regulate the expression of myocardial Cu-Zn-SOD in type 1 diabetic rats, which may lessen the myocardial damage induced by oxidative stress. Key words: Diabetes mellitus, type 1; Diabetic cardiomyopathies; Glucagon-like peptide-1