Effects Of RAAV2/1-Acrp30 On Insulin Resistance And Expression Of PPAR-γ In The Atherosclerosis GK Rats

Objectives:To investigate the possible mechanisms of protective effects of adiponectin on type 2 diabetic arteriosclerosis.Methods:Type 2 diabetic atherosclerotic rat models were established by feeding GK rats with high-fat diet and L-N-arginine-methylesten intragastric gavage.After 8 weeks,a total number of 30 atherosclerotic GK rat models were successfully achieved,and they were divided into 3 groups randomly,â‘ Model 1(M1)group:hind limb intramuscular injection of normal saline;â‘¡Model 2(M2)group:hind limb intramuscular injection of simple adeno-associated viruses;â‘¢the therapeutic(T)group:hind limb intramuscular injection of recombinant adeno-associated virus 2/1(rAAV2/1-Acrp30)with a dose of 1×10¹²v.g/ml.After 4 weeks of the experiment,blood was drawn from the orbital vein of the rats to measure the levels of fasting blood glucose (FBG),postprandial blood glucose(PBG)and insulin.At the end of the 8^th week,rats were sacrificed for further determination of serum hs-CRP concentration and PPARγmRNA expression in the aorta by semi-quantitative RT-polymerase chain reaction(RT-PCR).Results:(1)After 8 weeks of high-fat diet and L-N-arginine-methylesten intragastric gavage,characteristics changes of atherosclerosis were observed in aortas of model rats,such as massive foam cells,swell and discontinuous endothelial cells.(2)Compared with the control model groups(M1 and M2),the levels of fasting blood glucose(FBG)and 2-hour postprandial blood glucose(PBG)in therapeutic group(group T)were significantly decreased,their HOMA-IR also decreased significantly and ISI increased significantly(all p＜0.05), while no significant difference was found in serum insulin levels among group M1,M2 and T.(p＜0.05)(3)Compared with group M1 and M2,serum high sensitive C-reactive protein(hs-CRP)levels in group T decreased significantly(p＜0.05)(4)PPARγmRNA expressed in aortas of atherosclerotic rats.Compared with the atherosclerotic control model groups(group M1 and M2),PPARγmRNA expression in aortas of group T rats was significantly up-regulated(p＜0.05)Conclusions:(1)Type 2 diabetic atherosclerotic rat models can be successfully established by feeding GK rats with high-fat diet and L-NAME intragastric gavages.(2)rAAV2/1 -Acrp30 can lower glucose levels of atherosclerotic GK rats, and improve their insulin resistance.(3)The protective effects of adiponectin on T2DM atherosclerosis may produced by up-regulation of PPARγgene expression and lowering of hs-CRP concentrations in plasma.