关键词: 瑞马唑仑, 肝脏缺血/再灌注损伤, 氧化应激, 炎性反应, 凋亡

Abstract: Objective To investigate the effects of remazolam (REM) pretreatment on systemic oxidative stress, inflammation and apoptosis of liver cells in hepatic ischemia-reperfusion injury (HI/RI) rats. Methods Thirty SPF-grade male SD rats with body weight of 220-280 g, were randomly divided into 3 groups (n=10): sham operation group (sham group, only laparotomy), model group (HI/R group, a model was established with 70% liver ischemia for 60 minutes and then reperfusion for 6 hours), and intervention group (REM group, REM 10 mg/kg was injected via the tail vein 10 minutes before liver ischemia). Six hours after reperfusion, the rats were euthanized and vena cava blood and specimens of the left lobe of the liver were collected. Serum AST and ALT level were detected using an automatic biochemical analyzer. Serum level of the pro-inflammatory cytokines TNF-α, IL-1β, and IL-6 was measured by ELISA. Hepatic histo-pathological changes were observed using HE staining microscopy. The content of MDA was detected by thiobarbituric acid (TBA), and the activity of SOD was checked by xanthine oxidase (XOD). The expression of apoptosis-related proteins Bax and Bcl-2 was detected by Western blot. The apoptosis index (AI) of liver tissue cells was detected by TUNEL. Results After ischemia-reperfusion treatment, the expression of serum liver enzymes(AST,ALT) and pro-inflammatory mediators(TNF-α, IL-1β, IL-6) in the HI/R group were significantly higher than those in the sham group(P＜0.01). The expression of lipid peroxidation product MDA and pro-apoptotic protein Bax in liver tissue was significantly increased(P＜0.01). The activity of endogenous antioxidant enzyme SOD and the expression of anti-apoptotic protein Bcl-2 and AI of liver cells were significantly decreased(P＜0.01). After pretreatment with remimazolam, the expression levels of AST, ALT, TNF-α, IL-1β and IL-6 in the serum of the REM group were significantly lower than those in the HI/R group(P＜0.01). The expression of MDA and Bax protein in liver tissue was significantly decreased(P＜0.01). While the activity of SOD and the expression of Bcl-2 protein were significantly increased(P＜0.01). The AI of liver cells was significantly decreased(P＜0.01). Conclusions REM pretreatment can alleviate HI/R-induced hepatic dysfunction via multi-targeted mechanisms: inhibition of systemic oxidative stress, reduction of inflammation and alleviation of hepatocyte apoptosis.

Key words: remazolam, hepatic ischemia-reperfusion injury, oxidative stress, inflammation, apoptosis