Abstract

Background: Cerebral ischemia reperfusion (CIR) injury is the main pathological mechanism of ischemia stroke, and oxidative stress (OS) plays a vital role during the process of CIR. Recent studies have found that OS can activate MAPK pathway, which mainly functions as a mediator of cellular stresses. It revealed that H2S may exhibit multiple biological functions as a neuroprotector through protecting against OS-induced neuronal injury. But how H2S can attenuate ischemia/reoxygenation injury through MAPK signaling is not clear. The protective mechanism of exogenous hydrogen sulfide (H2S) on oxygen glucose deprivation/reoxygenation (OGD/R) at physiological doses in SH-SY5Y cells were investigated in this study.

Methods: DCFH- DA probe is used to measure intracellular ROS, Real-time PCR and Western blot are used to detect the levels of p38 MAPK, ERK3 and Nrf2. CCK-8 is used to detect cell viability.

Results: Comparing with the normal control group, the expressions of ERK3, p38MAPK and Nrf2 mRNA in other three groups were downregulated at the beginning of 24h. After 24h, the expressions of ERK3, p38MAPK and Nrf2 were upregulated significantly compared with the normal control group. When the cells were pretreated with 200μM NaHS at the beginning of 24h, the expressions of ERK3, p38MAPK and Nrf2 were decreased much more significantly than OGD/R and NaHS groups.

Conclusion: The present study demonstrated that exogenous H2S exerts a protective effect against OGD/R-induced injury by enhancing the activation of the ERK3, p38MAPK and Nrf2 mRNA.

Keywords: Hydrogen sulfide, oxygen-glucose deprivation, reoxygenation, ERK3, p38MAPK, Nrf2.