Improving effect of ursolic acid on glycolipid metabolism,inflammatory reaction and oxidative stress in pregnant GDM rats by regulating TLR4/MyD88/NF-κB pathway
Objective To investigate improving effect of ursolic acid(UA)on glycometabolism and lipid metabolism,inflammatory reaction and oxidative stress in pregnant rats with gestational diabetes mellitus(GDM)by regulating Toll like receptor 4(TLR4)/myeloid differentiation factor 88(MyD88)/nuclear factor-κB(NF-κB)pathway.Methods The rats model of GDM was established.The rats with GDM were divided into six groups:GDM group,low dose UA group(UA-L group),medium dose UA group(UA-M group),high dose UA group(UA-H group),metformin group and normal control group of rats fed with regular feed(NC group),with 10 rats in each group.The fasting blood glucose(FBG)level was tested by blood glucose meter,fasting insulin(FINS)was tested by radioimmunoassay,the levels of blood lipids profile as triglyceride(TG),total cholesterol(TC),low-density lipoprotein cholesterol(LDL-C)and high-density lipoprotein cholesterol(HDL-C)were tested by automatic biochemical analyzer.Enzyme-linked immunosorbent assay(ELISA)was used to detect lipid metabolism related enzymes as hepatic lipase(HL)and lipoprotein lipase(LPL)levels,and serum inflammatory factors including serum tumor necrosis factor-α(TNF-α),interleukin-1β(IL-1β),interleukin-2(IL-2)and interleukin-4(IL-4)levels.The levels of oxidative stress factors as malondialdehyde(MDA),superoxide dismutase(SOD),catalase(CAT)and glutathione peroxidase(GSH-Px)were detected by micro method.Western blot method was used to detect peroxisome proliferator activated receptor γ(PPARγ)and TLR4/MyD88/NF-κB pathway protein of the rats.Results Compared with the NC group,the levels of FBG,TG,TC,LDL-C,TNF-α,IL-2,IL-1β,and MDA,and expression levels of TLR4,MyD88,p-NF-κB p65/NF-κB p65 proteins of the rats in the GDM group were significantly higher,while their levels of FINS,HL,LPL,IL-4,CAT,SOD and GSH-Px,and expression of PPARγ protein were significantly lower,the differences were significant(all P＜0.05).Compared with the GDM group,the levels of FBG,TG,TC,LDL-C,TNF-α,IL-2,IL-1β,MDA,expressions of TLR4,MyD88,p-NF-κB p65/NF-κB p65 proteins of the rats in the metformin group and different UA doses groups were significantly lower,while their levels of FINS,HL,LPL,IL-4,CAT,SOD,GSH-Px,and expression of PPARγ protein were significantly higher,and the differences were significant(all P＜0.05).There was no significant difference in HDL-C level among all groups(P＞0.05),and also there were no significant differences in the above indexes between the metformin group and UA-H group(all P＞0.05).Conclusion UA could improve glucose metabolism and lipid metabolism,inflammatory reaction and oxidative stress in the GDM rats by down-regulating expression of TLR4/MyD88/NF-κB pathway proteins.
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