Abstract： Objective To investigate the role of COX- 2/PGE2 pathway in protective effects of hydrogen sulfide against chemical hypoxia-induced injury to human skin keratinocytes (HaCaT cells).Methods The hypoxia-mimicking agent CoCl2 was used to process HaCaT cells and establish an in vitro model of hypoxia-induced skin injury.Before the exposure to CoCl2,HaCaT cells were pretreated with NaHs (a donor of H2S) for 30 mins.The impact of H2S on CoCl2-induced cell injury was then detected.The cell survival rate was determined by cell counting kit (CCK)- 8,the expression level of PGE2 in culture medium by enzyme-linked immunosorbcnt assay (ELISA) and the expression levels of COX-1 and COX-2 protein by Western blot assay.Results The 24 h treatment of HaCaT cells with 500 μmol/L CoCl2 could significantly lower the cell survival rate[ (56.3±5.4)％],promote the release of PGE2[ (395.7±65.0)％] and up-regulate the expression of COX-2 (all P＜0.01).However,the treatment using CoCl2 did not obviously affect the expressions of COX - 1 in HaCaT cells (P＞0.05).The pretreatment with NaHs (ranging from 200 to 400 μmol/L) could significantly inhibit the lowered cell survival,increascd rclcase of PGE2 and up-regulated expression of COX-2 caused by CoCl2.Additionally,NS-398,a selective inhibitor of COX-2,could also inhibit CoCl2-induced decrease in cell survival rate.Conclusions H2S can antagonize the chemical hypoxiainduced injury and protect HaCaT cells.Furthermore,this mechanism is associated with the inhibition of COX-2/PGE2 pathway.