Exogenous hydrogen sulfide reduces focal cerebral ischemia/reperfusion injury in rats via nuclear factor-κB-mediated inflammatory response pathway

Objective To investigate the effect of hydrogen sulfide (H2S) on brain injury and inflammatory response after cerebral ischemia/reperfusion in rats. Methods Forty-eight male SD rats were randomly divided into four groups: sham operation group, ischemia/reperfusion (I/R) group, H2S-30 ppm group, and H2S-60 ppm group (n=12 in each group; 1 ppm=1 mg/L). The middle cerebral artery occlusion method was used to induce a model of focal cerebral ischemia for 2 h and reperfusion for 24 h. After reperfusion for 24 h, the tape remove experiment was used to perform the nerve function evaluation. 2, 3, 5-triphenyl-tetrazolium chloride staining method was used to measure the percentage of cerebral infarction volume. Enzyme-linked immunosorbent assay was used to measure the levels of interleukin (IL) -1β and IL-6. Western blotting was used to detect the expression levels of inducible nitric oxide synthase (iNOS) and intercellular cell adhesion molecule-1 (ICAM-1) , as well as the transposition activation of nuclear factor-κB (NF-κB). Results Inhalation of H2S could shorten the time required to remove the tape in a dose-dependent manner compared with the I/R group (I/R group vs. H2S 30 ppm group and H2S 60 ppm group: 180 s vs. 130 [113-157]s vs. 110 [87-138] s; P<0.05), reduced the cerebral infarct volume (48.8%±9.1%vs. 23.3%±5.1% vs. 17.3%±3.5%; P<0.05), downregulated the expression levels of IL-1β (39.53±6.02 pg/mg protein vs. 30.17±3.46 pg/mg protein vs. 22.69±6.09 pg/mg protein; P<0.05) and IL-6 (54.65±10.68 pg/mg protein vs. 37.89±4.54 pg/mg protein vs. 27.00±3.08 pg/mg protein; P<0.05) in ischemic brain tissue, significantly decreased NF-κB nucleus/cytoplasm ratio (4.40±1.05 vs. 3.07±0.82 vs. 2.30±0.60; P<0.05), inhibited expressions of iNOS (4.22±0.67 vs. 3.14±0.90 vs. 2.08±0.35; P<0.05), and ICAM-1 (5.45±1.08 vs. 3.45±0.67 vs. 2.21±0.39; P<0.05). Conclusions Inhalation of exogenous H2S can reduce cerebral infarct volume after cerebral ischemia/reperfusion in a dose-dependent manner and improve neurological function. Its mechanism may be associated with the inhibition of NF-κB activation, down-regulation of its downstream iNOS and ICAM-1 expression levels, and decrease of IL-1β and IL-6 levels. Key words: Brain Ischemia; Reperfusion Injury; Hydrogen Sulfide; Inflammation; NF-κB; Neuroprotective Agents; Disease Models, Animal; Rats