| Objective:Type 2 diabetes mellitus(T2DM)is the most independent factor of liver fibrosis and all-cause death in NAFLD(NAFLD).The common etiology of both is insulin resistance(IR),but the mechanism of action is still not clear.Phosphorylation of insulin receptor substrate 1(IRS-1)and decreased activity of the PI3K-Akt signaling pathway may play important roles in the key effects of IR.Therefore,this research by feeding high-fat diet(HFD)28 weeks induced rat merger of NAFLD pre-diabetes(Pre)model is established,PI3 K,Akt signaling pathways IGM NAFLD patients occurred under the potential mechanism,and through the Lycium Barbarum Polysaccharides(LBP)in combination with aerobic exercise for nonalcoholic fatty liver disease early intervention model rats with diabetes mellitus and observe whether can slow the progress of NAFLD after intervention,prevention and treatment of nonalcoholic fatty liver disease combined with pre-diabetes.Methods:90 SPF SD male rats with the body weight of(200 ± 20)g were purchased from the Ningxia Medical University Laboratory Animal centre with the production license No.: SCXK(Ning)2015-0001.SD rats were kept in SPF laboratory of Animal Experimental Center,and diet and water were not restricted during the experiment.The 90 rats were divided into control group(20 rats)and model group(70 rats).The control group was fed with normal diet and the model group was fed with high fat diet.The rats in the two groups were fed continuously for 28 weeks to establish the model.In the intervention stage,6 rats were randomly selected from the control group,and 24 of the 43 rats were randomly selected and randomly divided into model group(6 rats),LBP group(6 rats),aerobic exercise group(6 rats)and combined intervention group(6 rats).From week 29,the rats in blank group and model group were gavaged with 0.9 % normal saline 2 mL,the rats in polysaccharide group were gavaged with 0.1 g/kg 2 mL,the rats in exercise group were gavaged with0.9 % normal saline 2 mL,and the rats in exercise group were gavaged with 1000 m/h exercise amount for 60 min,and the rats in combined group were gavaged with polysaccharide group and exercise group.The intervention lasted for 8 weeks.Serum samples of TNF-α,IL-2,IL-6,IL-10,TGF-β1,CRP,NF-κB p65,C-P,ALT and ALP were detected by ELISA.GPO method was used to detect lipid related indexes.The plasma free fatty acid profiles of rats in each group were detected by targeted GC-MS.WB method was used to detect the expression of PI3K/Akt signaling pathway-related proteins in liver and pancreas tissues of rats in each group.Results:1.After 28 weeks of feeding with high fat diet,the OGTT and ITT test results of the control group and the model group showed that the blood glucose values of the model group at each time point of the OGTT and ITT test were significantly higher than those of the control group(P < 0.05).2.At the end of 8 weeks after intervention,OGTT and ITT were measured,and there were statistically significant differences in the blood glucose levels of OGTT at0,30,60,90 and 120 min among the five groups(P < 0.05).3.Compared with blank group,the contents of TNF-α,IL-6,IL-10,TGF-β,CRP and NF-κB in model group were significantly increased(P < 0.05);Compared with model group,the levels of inflammatory cytokines in polysaccharide group,exercise group and combined group were significantly decreased(P < 0.05).Among polysaccharide group,exercise group and combined group,combined group had the best effect on improving body inflammation.4.Compared with blank group,the levels of TC,TG,LDL-C,C-P,ALT and AST in model group were significantly increased(P < 0.05),while HDL-C was significantly decreased(P < 0.05);Compared with model group,the levels of TC,TG,LDL-C,C-P,ALT and AST in polysaccharide group,exercise group and combined group were significantly decreased(P < 0.05),while HDL-C was significantly increased(P < 0.05).Compared with polysaccharide group,TG level in exercise group was significantly increased(P < 0.05).Compared with exercise group,the level of TG in combined group was significantly decreased(P < 0.05).Compared with polysaccharide group,AST level in exercise group and combined group was significantly decreased(P < 0.05).5.Compared with model group,the plasma levels of total fatty acids and saturated fatty acids in polysaccharide group,exercise group and combined group were significantly decreased(P < 0.05),while the plasma levels of various unsaturated fatty acids were significantly increased(P < 0.05).Compared with polysaccharide group,the levels of unsaturated fatty acids and monounsaturated fatty acids in exercise group and combined group were significantly increased(P < 0.05),but the effect of combined intervention was better.After using OPS-DA analysis,the distribution among each group was concentrated.The distribution of union group and blank group was more similar.6.Compared with blank group,the protein expression levels of INSR,IRS-2,PI3 K,Akt,p-Akt and Glut-4 in model group,polysaccharide group,exercise group and combined group were significantly decreased(P < 0.05);Compared with model group,the protein expression levels of INSR,IRS-2,PI3 K,Akt,p-Akt and Glut-4 in polysaccharide group,exercise group and combined group were significantly increased(P < 0.05).The protein expression levels of INSR,IRS-2,PI3 K,Akt,p-Akt and Glut-4 in polysaccharide group,exercise group and combined group were all increased,and the protein expression of up-regulation of PI3K/Akt signaling pathway was the highest in the combined group.Conclusion:1.Aerobic exercise combined with LBP intervention can reduce the levels of inflammatory factors and blood lipid in model rats,and improve insulin resistance in model rats.2.Aerobic exercise combined with LBP can increase the contents of saturated fatty acids and unsaturated fatty acids in plasma of rats with NAFLD complicated with pre-diabetes.3.Aerobic exercise combined with LBP can up-regulate the protein expression levels of INSR,IRS-2,PI3 K,Akt,p-Akt and Glut-4 in the PI3K/Akt signaling pathway of rats with NAFLD and prediabetes,which may be the potential molecular mechanism for the prevention and treatment of NAFLD and prediabetes. |
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