The expression of cystathionine β-synthase and the level of hydrogen sulfide in neonatal rats with hypoxic-ischemic brain damage and the effect of zinc protoporphyrin

Objective To study the relationship between the expression of cystathionine β-synthase(CBS) and the level of hydrogen sulfide(H2S)in neonatal rats with hypoxic-ischemic brain damage(HIBD)and to detect the effect of the heme oxygenase-1(HO-1)inhibitor,zinc protoporphyrin-Ⅸ(Znpp-Ⅸ),on the expression of CBS mRNA and the level of H2S for exploring the theoretical evidences and the clinical perspective of the therapeutic effect of the ectogeneic Znpp-Ⅸ in neonatal hypoxic-ischemic encephalopathy(HIE).Methods The HIBD models were produced in the 7-day-old Wistar rats.The rats were then divided into 3 groups randomly,sham operation(control)group(n = 35),HIBD group(n = 38),and HIBD + Znpp group(n = 37).In HIBD + Znpp group,Znpp-IX(45 μmol/kg)were injected intra-peritoneally 30 minutes before hypoxic-ischemic(HI)insult.The rats were killed at 3,6,12,18,24 h after HI insult.The plasma level of H2S was detected by the spectrophotometer.The expression levels of CBS mRNA and bcl-2 protein were examined by in situ hybridization and immunohistochemistry respectively.Results The plasma H2S level and the expression of CBS mRNA in both HIBD group and HIBD + Znpp group were increased significantly at 3 h after HI insult,peaked at 12 h and then decreased over time.The plasma H2S level and expression of CBS mRNA in HIBD + Znpp group were higher than HIBD group at each different time point(P 0.01).The expression of bcl-2 protein in HIBD group was increased significantly at 3 h after HI insult,peaked at 12 h and then decreased over time.The expression of bcl-2 protein in HIBD + Znpp group was increased significantly at 3 h after HI insult,peaked at 18 h and then decreased.The expression were higher than HIBD group at each different time point(P 0.01).Conclusions The expression of CBS and the H2S level were up-regulated during HIBD,which can protect brain against HI injury by up-regulating the expression of bcl-2.Ectogeneic HO-1 inhibitor,Znpp-Ⅸ,might up-regulate the expression of CBS and the H2S level to improve or avoid HIBD.