Exogenous hydrogen sulfide reduces focal cerebral ischemia/reperfusion injury in rats via nuclear factor-κB-mediated inflammatory response pathway
10.3760/cma.j.issn.1673-4165.2016.10.011
- VernacularTitle:外源性H2S通过核因子-κB介导的炎性反应通路减轻大鼠局灶性脑缺血再灌注损伤
- Author:
Xia WEI
;
Long CHENG
;
Qingqing WANG
;
Bing ZHANG
- Keywords:
Brain Ischemia;
Reperfusion Injury;
Hydrogen Sulfide;
Inflammation;
NF-κB;
Neuroprotective Agents;
Disease Models,Animal;
Rats
- From:
International Journal of Cerebrovascular Diseases
2016;24(10):918-923
- CountryChina
- Language:Chinese
-
Abstract:
Objective To investigate the effect of hydrogen sulfide (H2S) on brain injury and inflammatory response after cerebral ischemia/reperfusion in rats.Methods Forty-eight malc 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)-1 β 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.
