| Objective:To investigate the effect of eight weeks aerobic exercise and metformin on vascular endothelial function,glycolipid metabolism,inflammatory response and the protein expression of LOX-1,NF-κBp65 and Caspase-3 in aorta of type 2 diabetic mice.Methods:In this experiment,80 male C57BL/6J mice were fed with normal diet for one week.They were randomly divided into the normal group(24,N)and the type 2 diabetes mellitus model group(56,D).The normal group was fed normal diet throughout the experimental period.Type 2 diabetic mice(T2DM)were established by multiple intraperitoneal injections of streptozotocin at 40mg/kg after 4 weeks of high-fat diet in the type 2 diabetes model group,while the normal group was injected with the same dose of citric acid buffer.After the successful modeling,the subjects were divided into diabetes control group(DC),diabetes aerobic exercise group(DA),diabetes metformin group(DM),diabetes exercise + metformin group(DAM),and the high-fat diet was continued to feed.The normal group was divided into the normal control group(NC)and the normal aerobic exercise group(NA).The exercise group received one week of adaptive exercise before 8 weeks of aerobic exercise with 75% maximum oxygen uptake.The metformin group was administered at a dose of 200mg/kg/day.Random blood glucose was measured weekly during the intervention.After intervention,lipid metabolism indexes were detected by corresponding kit;Serum NO level was detected by nitrate reductase;Serum insulin,endothelin-1,TNF-α and IL-1 β were detected by ELISA;The protein expression of LOX-1,NF-κBp65 and Caspase-3 in aorta were detected by Western blot analysis.Results:1 、 The AUC and FINS levels of type 2 diabetic mice induced by STZ were significantly increased compared with the normal group(P < 0.01).After the successful modeling of type 2 diabetic mice,TC,TG,and LDL-C of D group were significantlyincreased than N group(P < 0.01),and HDL-C of D group were significantly decreased than N group(P < 0.05).The protein expressions of eNOS,VCAM-1 and Caspase-3 in aorta of D group were not significantly different from those of N group(P > 0.05),and the protein expressions of ox-LDL,LOX-1,NF-κ Bp65 in aorta of D group were significantly increased(P < 0.01 or P < 0.05).2、Before intervention,there was no significant difference in blood glucose level between NA group and NC group(P > 0.05);The blood glucose levels of DC group,DA group,DM group and DAM group were significantly higher than NC group(P < 0.01),and there was no significant difference in blood glucose levels between DC group,DA group,DM group and DAM group(P > 0.05).After intervention,there was no significant difference in blood glucose level between NA group and NC group(P > 0.05).The blood glucose level of DC group,DA group,DM group and DAM group was significantly higher than NC group(P < 0.01).The blood glucose level of DA group,DM group and DAM group was significantly higher than DC group(P < 0.01),and there was no significant difference between DA group,DM group and DAM group(P > 0.05).After the intervention,the blood glucose levels of NC group,NA group,DA group,DM group and DAM group were not significantly different from those before the intervention(P > 0.05),while the blood glucose levels of DC group were significantly higher than those before the intervention(P < 0.01).During the intervention period,the blood glucose levels of NC group and NA group were basically stable.The blood glucose level of DC group showed continuous rising trend.The blood glucose levels of DA group,DM group and DAM group remained basically stable within 5 weeks intervention prior,and began to decline from the 5th week.3、After 8 weeks of aerobic exercise,the level of FBG,FINS,HOMA-IR and INS in NA group had no significant difference compared with NC group(P > 0.05).At the end of the intervention,the level of FBG,FINS and HOMA-IR of DC group,DA group,DM group and DAM group were significantly increased compared with NC group(P < 0.05 or P < 0.01),while INS levels were significantly decreased(P < 0.01).After the intervention of aerobic exercise and metformin,the level of FBG,FINS and HOMA-IR of DA group,DM group and DAM group were significantly decreased compared with DCgroup(P < 0.01),and INS level was significantly increased(P < 0.01).The level FBG,FINS,HOMA-IR and INS levels of DA group had no significant difference compared with DM group and DAM group(P > 0.05).The level of FBG of DAM group had no significant difference compared with DM group(P > 0.05),the level FINS and HHOMA-IR significantly decreased(P < 0.05),and INS significantly increased(P <0.01).4、After 8 weeks of aerobic exercise,TC and TG of NA group were significantly lower than those in the NC group(P < 0.05 or P < 0.01),while LDL-C showed no significant difference(P > 0.05)and HDL-C significantly increased(P < 0.01).Compared with NC group,TC,TG and LDL-C in DC group,DA group and DM group were significantly increased(P < 0.05 or P < 0.01),while HDL-C was significantly decreased(P < 0.05 or P < 0.01).TC in DAM group was significantly higher than that in NC group(P < 0.05),while TG,LDL-C and HDL-C showed no significant difference(P > 0.05).There were no significant differences in TC,TG,LDL-C and HDL-C between the DA group and the DM group(P > 0.05).TC in DAM group was significantly lower than that in DA group(P < 0.01),and there was no significant difference compared with that in DM group(P > 0.05).There was no significant difference in TG and LDL-C between DAM group and DA group(P > 0.05),which was significantly lower than that in the DM group(P < 0.01).HDL-C in DAM group was not significantly different from that in DA group(P > 0.05),but significantly higher than that in DM group(P < 0.05).5、After 8 weeks of aerobic exercise,TNF-α in NA group was significantly lower than that in NC group(P < 0.05),while there was no significant difference in IL-1β(P >0.05).The level of TNF-αand IL-1βin DC group were significantly higher than those in NC group(P < 0.05),while the level of TNF-αand IL-1βin DA group,DM group and DAM group were not significantly different from those in NC group(P > 0.05).After the intervention,the levels of TNF-αand IL-1βin DA group,DM group and DAM group were significantly lower than those in DC group(P < 0.05 or P < 0.01).The levels of TNF-αand IL-1βin the DA group were not significantly different from those in DM group(P > 0.05).The level of TNF-αin DAM group was significantly lower than that in DA group(P < 0.05),and there no significant difference between DAM group and DMgroup(P > 0.05).The level of IL-1βin DAM group was no significant difference from those in DA group and the DM group(P > 0.05).All FINS had significant positive correlation with TNF-and IL-1β(P < 0.05 or P < 0.01),while HOMA-IR had significant positive correlation with TNF-(P < 0.05),but there was no correlation with IL-1β(P >0.05).6、After 8 weeks of aerobic exercise,the level of NO and NO/ET-1 in NA group were significantly higher than those in NC group(P < 0.05 or P < 0.01),while there was no significant difference in ET-1(P > 0.05).The level of NO in DC group was significantly lower than that in NC group(P < 0.01),the level of NO in DA group,DM group and DAM group was not significantly different from that in DC group(P >0.05).The level of ET-1 in DC group,DA group,DM group and DAM group was significantly higher than NC group(P < 0.01),and NO/ET-1 was significantly lower(P <0.05 or P < 0.01).After the intervention,the level of NO and NO/ ET-1 in DA group and DAM group were significantly increased(P < 0.05 or P < 0.01),while ET-1 was significantly decreased(P < 0.01).There was no significant difference in NO and NO/ET-1 between DM group and DC group(P > 0.05),and the level of ET-1 was significantly lower than DC group(P < 0.01).The level of NO and NO/ ET-1 in the DA group were not significantly different from those in DM group(P > 0.05),and the level of ET-1 levels were significantly reduced(P < 0.01).The level of NO in DAM group showed no significant difference compared with DA group and DM group(P > 0.05),and the level of ET-1 was significantly decreased(P < 0.01),and NO/ET-1 was significantly increased(P < 0.01).7、After 8 weeks of aerobic exercise,the protein expression of eNOS in NA group was significantly increased than that in NC group(P < 0.01),ox-LDL,NF-Bp65,and VCAM-1 were significantly decreased(P < 0.05 or P < 0.01),while the protein expression of LOX-1 and Caspase-3 were not significantly different(P > 0.05).The protein expression of eNOS in DC group was significantly lower than that in NC group(P < 0.01),and there was no significant difference between DA group and DM group(P >0.05).The protein expression of eNOS in DAM group was significantly increased compared with NC group(P < 0.01).The protein expressions of ox-LDL,LOX-1,NF-κBp65 and VCAM-1 in DC group,DA group,DM group and DAM group were significantly higher than those in NC group(P < 0.05 or P < 0.01).The protein expressions of Caspase-3 in DC group and DM group were significantly higher than those in NC group(P < 0.05 or P < 0.01).The protein expressions of Caspase-3 in DA group and DAM group were not significantly different from those in NC group(P > 0.05).After the intervention,the protein expression of eNOS in DA group,DM group and DAM group was significantly increased than that in DC group(P < 0.01),ox-LDL,LOX-1,NF-κ Bp65 and Caspase-3 were significantly decreased(P < 0.05 or P < 0.01);and the protein expressions of VCAM-1 in DA group and DAM group was significantly decreased than that in DC group(P < 0.01),while there was no significant difference in DM group(P > 0.05).Compared with DA group and DM group,the protein expression of eNOS in DAM group was significantly increased(P < 0.01),the protein expression ox-LDL,LOX-1,NF-κB p65 and Caspase-3 were significantly decreased(P < 0.05 or P< 0.01).The protein expression of VCAM-1 in DAM group was significantly lower than that in DM group(P < 0.01),and there was no significant difference compared with that in DA group(P > 0.05).The protein expressions of eNOS,NF-B p65 and caspase-3 in the DA group were not significantly different from those in the DM group(P > 0.05),and the protein expressions of ox-LDL,LOX-1 and VCAM-1 were significantly lower than those in DM group(P < 0.05 or P < 0.01).Conclusion:1、Type 2 diabetic mice had disorder of blood lipid metabolism,and there is some degree of inflammation in the aorta.2、After the intervention of aerobic exercise,metformin and aerobic exercise combined with metformin for 4 weeks,the blood glucose of type 2 diabetic mice showed a steady decline.3、The intervention of aerobic exercise,metformin and aerobic exercise combined with metformin can effectively improve the insulin resistance,lipid metabolism,reduce the inflammatory reaction,inhibit the apoptosis of vascular cells and improve the vasodilatory function in type 2 diabetic mice.4、Aerobic exercise has a more significant effect than metformin in reducingvascular inflammation,and the intervention of aerobic exercise combined with metformin is more effective than that of single aerobic exercise or metformin in improving blood lipid metabolism,reducing body inflammation and improving vasodilatory function in type 2 diabetic mice. |
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