Protective effect of hydrogen sulfide on pressure ulcer rats with ischemia/reperfusion injury and its mechanisms

Objective To explore the protective effect and mechanism of exogenous hydrogen sulfide (H2S) on pressure ulcer rats with ischemia/reperfusion (I/R) injury. Methods Forty SD rarts were randomly divided into 4 groups, namely normal control group, I/R model group, low-dose H2S intervention group and high-dose H2S intervention group.Each group had 10 animals.The low-and the high-dose H2S intervention groups were injected intraperitoneally 10 and 30 μmol/kg of sodium hydrosulfide (NaHS) for 1 week, respectively; however, the normal control group and I/R model group were treated with same volume 9 g/L saline.Then, the normal control group did not sustain any pressure, but other 3 groups were pressurized.After 3 circulations of ischemia/reperfusion, all rats were sacrificed, and pathological changes in pressure ulcer rats were evaluated by HE staining.Serum H2S contents were analyzed through methylene spectrophotometric method.Serum levels of tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), intercellular adhesion molecule -1 (ICAM-1), and myeloperoxidase (MPO) were detected by enzyme linked immunosorbent assay (ELISA). The activities of malondialdehyde (MDA), superoxide dismutase (SOD), glutathione-peroxidase (GSH-Px) and catalase (CAT) in the homogenate of muscle were examined.Apoptotic index (AI) was calculated by terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL). The expressions of Bcl-2 and Bax in muscle tissue were evaluated by Western blot. Results In comparison with the normal control group, serum TNF-α, IL-6, ICAM-1 and MPO levels, MDA activity in the homogenate of muscles, AI and Bax expression level were increased (all P<0.01), while serum H2S levels, the activities of SOD, GSH-Px and CAT as well as Bcl-2 expression levels were reduced in the I/R model group (all P<0.01). Upon intervention therapy of low- or high-dose H2S, pathological scores, serum TNF-α, IL-6, ICAM-1 and MPO levels, MDA activity in the homogenate of muscle, AI and Bax expression levels were gradually reduced while serum H2S levels, the activities of SOD, GSH-Px and CAT and Bcl-2 expression levels were gradually enhanced when compared to those of the I/R model group (all P<0.05, 0.01). Conclusions Exogenous H2S has better protection against pressure ulcer rats with I/R injury.The mechanism may be associated with inhibition of inflammatory reaction and enhancement of antioxidative ability as well as reduction of apoptosis. Key words: Hydrogen sulfide; Pressure ulcer; Ischemia/reperfusion; Oxidative stress; Apoptosis