Effects of liraglutide on myocardial autophagy and lipid deposition in early diabetic rats / 中华内分泌外科杂志

ABSTRACT

Objective:To investigate the effects of liraglutide on the expressions of autophagy markers LC3B, LC3B mRNA and lipid deposition in myocardial tissue of rats with early diabetes mellitus.Methods:A total of 36 healthy male Wistar rats aged 4-5 weeks and weighing (l80-200) g were selected and divided into normal group (group NC, 10 rats) and model group (26 rats) according to random number table. Rats in the NC group were fed with routine diet and rats in the model group were given high glucose and high fat diet for 12 weeks. Rats in the model group were injected with streptozotocin into the abdominal cavity in a single dose of 25 mg/kg after molding. Rats in the model group were further divided into three groups T2DM group (group DM/NS, 9 rats, given equal volume of saline) , liraglutide intervention group (group DM/LIR, 8 rats, injected with 100 μg/kg liraglutide twice daily) and Liraglutide and Chloroquine intervention group (group DM/LIR+CQ, 8 rats, injected with 100 μg/kg liraglutide twice daily, and injected with Chloroquine 50 mg/kg once every two days) . Rats in group NC were given equal volume of saline. At the end of 12 weeks, all the rats were tested blood glucose and anaesthetized to collect myocardial tissues to observe myocardial lipid deposition and fiber arrangement under light microscope after HE staining. The expressions of LC3B were detected by immunohistochemical method, and the expressions of LC3B mRNA were detected by real-time fluorescence quantitative polymerase chain reaction method. Differences among groups were compared by one-way analysis of variance, pairwise comparison was conducted by using LSD-t test, correlation was analyzed by Pearson correlation.Results:(1) Compared with group NC, the myocardial fibers arranged in disorder, and the ratio of myocardial foam cells/total cardiomyocytes were increased, the level of LC3B mRNA and LC3B were decreased in group DM/NS and DM/LIR+CQ (in group DM/NS 2.18±0.90 vs 11.79±0.74, 2.03±0.10 vs 1.85±0.06, 194.18±10.19 vs 175.99±6.09, t=25.24, 4.69, 3.22, respectively; in group DM/LIR+CQ 2.18±0.90 vs 11.24±1.29, 2.03±0.10 vs 1.89±0.08, 194.18±10.19 vs 176.73±7.82, t=17.56, 4.65, 3.99, respectively, all P<0.05) . There is no difference in above indicators (2.18±0.90 vs 1.29±0.60, 2.03±0.10 vs 2.01±0.20, 194.18±10.19 vs 201.27±11.35, t=2.20, 0.28, 1.40, respectively, all P>0.05) . (2) Compared with group DM/NS, the ratio of myocardial foam cells/total cardiomyocytes, the level of LC3B mRNA and LC3B were no difference in group DM/LIR+CQ ( t=1.09, 1.18,0.22, respectively, all P>0.05) . The ratio of myocardial foam cells/total cardiomyocytes was decreased, the level of LC3B mRNA and LC3B were increased in group DM/LIR (11.79±0.74 vs 1.29±0.60, 1.85±0.06 vs 2.01±0.20, 175.99±6.09 vs 201.27±11.35, t=31.86, 2.39, 5.82, respectively, all P<0.05) . (3) The significant negative correlation were observed between the ratio of myocardial foam cells/total cardiomyocytes and LC3B mRNA, LC3B levels (r=-0.977, -0.986, respectively, all P<0.05) . Conclusion:Liraglutide can protect the myocardial structure in early diabetic rats by increasing myocardial autophagy, reducing the number of myocardial foam cells, and improving the myocardial lipid deposition.