关键词: NO供体, NF-kB, 白三烯C4合酶, 缺血再灌注损伤, 肝脏

Abstract: Objectives: To explore the mechanism underlying a selective liver nitric oxide donor V-PYRRO/NO effects on the gene expression of LTC4 synthase (LTC4S) during hepatic I/R. Methods: Adult male SD rats were divided into 3 groups: control group (Sham), ischemic-reperfusion group(I/R) and V-PYRRO/NO groups. Liver subjected to 1h of partial hepatic ischemia followed by 5 h of reperfusion, saline or V-PYRRO/NO(1.06mmol/kg/h) administered intravenously. The mRNA expressions of LTC4S in rat liver tissue were examined by RT-PCR method, the protein expressions of NF-κB p65, p50 and IκB? in liver cell lysates and nuclear extracts were detected by western blot analysis. Results: hepatic mRNA expression of LTC4S in I /R group was higher (P<0.05) than that in sham group whereas it was lower in V-PYRRO/NO group than that in I /R group (P<0.05). Moreover, compare with sham group, the protein expressions of NF-κBp65 and p50 in nucleus extract were markedly increased(P<0.01) but significantly decreased in cytoplasm(P<0.01) in I/R group. V-PYRRO/NO reversed completely the increase of these protein expressions in nucleus extract (P<0.05) and the decrease of them in cytoplasm (P<0.01, P<0.05) during hepatic I/R injury. However, IκB? protein in three groups not changed. Immunohistochemistry staining revealed that no marked positive staining for NF-κB p65 was presented in sham liver, I/R liver exhibited strong cytoplasmic and nuclear positive staining for NF-κB p65, but V-PYRRO/NO I/R group liver presented slight cytoplasmic and nuclear staining. Conclusions: V-PYRRO/NO might down-regulated LTC4S mRNA expression by inhibiting NF-κB activation independent of IκB? during hepatic I/R injury.

Key words: NO donor, NF-kB, Leukotriene C4 synthase, Ischemia reperfusion injury, Liver