The Effects And Mechanism Of The Different Levels Of Insulin On The Aorta In Rats Under High Fat Diet

Objective; To inspect the change of intima-media thickness of aorta under high fat diet rats with hyperinsulinemia, and to investigate it’s mechanisms by setting different insulin levels in Sprague Dawley rats fed with high fat diet.Methods:A total32male SD rats, health, aged8weeks, weight180-200g, were randomly divided into four groups:the ND group was fed with standard diet; the HFD group was fed with high fat diet; the HFD+INS group was fed with high fat diet and treated by insulin (INS); the HFD+STZ group was fed with high fat diet and treated by streptozotocin (STZ). After1week of acclimation period and abrosia for12hours, the HFD+STZ group was induced with a single intraperitoneal injection of STZ (50mg/kg), other groups were injected buffer at the same dose instead. Three days later, the HFD+INS group was induced with subcutaneous injection of lU/Kg long-acting insulin every morning, other groups were injected normal saline (NS) at the same dose instead. The changes of blood sugar and weight of rats were monitored. Used of color doppler ultrasound evaluation IMT of the aorta. The morphological changes of aorta tissues were observed through light microscopy after HE staining, the levels of body weight, FPG, TG, LDL-C, TC, HDL-C, FINS, HbAlc%were measured after4months. The HOMA-IR was evaluated. The expression of VEGF, TNF-α, PGC-1α, ApoE were analyzed by western blot.Results:1. Compared with the ND group, the IMT in groups of HFD and HFD+INS were increased for aboutl.53fold and1.92fold (P<0.05). The result was also found statistically significant when HFD group was compared with HFD+INS group. The IMT was no obvious difference in the group HFD+STZ and ND (P>0.05), but the IMT of the HFD+STZ group was thinner when compared with HFD group and HFD+INS group (P<0.05). The results of light microscopy after HE staining were the same as above, the IMT in HFD+INS group was the thickest. At the magnification, the vascular endothelial was incomplete and some foamy histiocytes could been saw. But no typical atherosclerotic plaques were observed in all groups.2. The levels of body weight, TG, TC, LDL-C, FINS, HOMA-IR were increased in the HFD and HFD+INS groups compared with the ND group (P<0.05). When compared with the HFD group, the levels of body weight, TG, TC, LDL-C, FINS, HOMA-IR in HFD+INS group is also increased (P<0.05). In the HFD+STZ group, the levels of body weight and insulin were lower than the ND group, and the levels of HbAlc%, TC, LDL-C were higher than the ND group (P<0.05), but the the levels of TG, HOMA-IR were not obvious change (P>0.05). Compared with the HFD+STZ group, the HFD and HFD+INS groups the levels of body weight, TG, TC, FINS, HOMA-IR increased, but the level of HbAlc%decreased (P<0.05). The change of HDL-C was insignificant in all groups.3. The expression of VEGF and TNF-α protein were increased in group of HFD+INS, when compared with ND and HFD groups, and the expression of PGC-la and ApoE protein were decreased significantly (P<0.05). In the group of HFD+STZ, the expression of VEGF and TNF-α protein were decreased, the expression of PGC-1α and ApoE protein were increased when compared with HFD and HFD+INS groups, all of these differences were significant (P<0.05).Conclusions:1. Early hyperinsulinemia may be contributor to the increase of IMT under high fat diet rats.2. Early hyperinsulinemia may cause the expression of VEGF and TNF-α protein were increased, the expression of PGC-1α and ApoE protein were decreased under high fat diet rats.