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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