Ameliorating effect of ursolic acid on trophoblast cell injury induced by high sugar during gestational diabetes mellitus and its mechanism
Objective To explore the effects of ursolic acid on high glucose-induced trophoblast cell damage and the underlying mechanisms.Methods Human HTR-8/SVneo trophoblast cells were divided into control group(5.5 mmol/L glucose),model group(25 mmol/L glucose),low-dose group(25 mmol/L glucose+1 μmol/L ursolic acid),medium-dose group(25 mmol/L glucose+3 μmol/L ursolic acid),and high-dose group(25 mmol/L glucose+5 μmol/L ursolic acid).Cell viability,cytotoxicity and apoptosis were detected by cell counting kit-8(CCK-8)assay,lactate dehydrogenase(LDH)cytotoxicity assay and flow cytometry,respectively.Enzyme-linked immunosorbent assay(ELISA)and corresponding kits were used to detect the levels of tumor necrosis factor-α(TNF-α),interleukin-10(IL-10),IL-1β,catalase(CAT),malondialdehyde(MDA)and superoxide dismutase(SOD).Western blot was used to measure the expressions of proteins in the Toll-like receptor 4(TLR4)/myeloid differentiation factor 88(MyD88)/nuclear factor-kappa B(NF-κB)pathway.Results Compared with those of the control group,cells in the model group presented significantly lower cell viability,protein expression of Bcl-2 and relative levels of IL-10,SOD and CAT,and significantly higher LDH release,apoptotic rate,protein expressions of Bax,TLR4,MyD88 and NF-κB and relative levels of TNF-α,IL-1β and MDA(P＜0.05).Compared with those of the model group,cells in the low-dose group,medium-dose group and high-dose group presented significantly higher cell viability,protein expression of Bcl-2 and relative levels of IL-10,SOD and CAT,and significantly lower LDH release,apoptotic rate,protein expressions of Bax,TLR4,MyD88 and NF-κB and relative levels of TNF-α,IL-1β and MDA(P＜0.05).Conclusion Ursolic acid prevents high glucose-induced trophoblast cell damage during GDM by inhibiting inflammation,oxidative stress and apoptosis through inhibiting the activation of the TLR4/MyD88/NF-κB pathway.
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