紫檀芪减轻小鼠肝窦内皮细胞氧化损伤的机制

Mechanism of pterostilbene reducing oxidative damage in endothelial cells in mouse hepatic sinus

目的探索天然的酚类化合物紫檀芪(pterostilbene,PTE)减轻小鼠肝窦内皮细胞氧化损伤的机制。方法40只C57小鼠分为对照组、模型组、治疗组建立70%肝脏缺血/再灌注(缺血60 min)模型,并通过灌注和消化法分离原代肝窦内皮细胞(liver sinusoidal endothelial cells,LSECs)。通过HE染色观察肝脏结构;透射电镜(TEM)观察肝窦内皮细胞超微结构;扫描电镜(SEM)观察LSECs窗孔的结构;Western blot检测LSECs内血红素氧化酶-1(heme oxygenase 1,HO-1)表达水平。结果HE染色显示,PTE能够改善肝脏缺血性损伤;TEM观察到PTE对肝窦内皮细胞具有保护作用;扫描电镜观察发现,空白对照组LSECs窗孔数量较多,模型组窗孔数量减少;与模型组比较,治疗组LSECs窗孔数量有所增加。Western blot结果显示,PTE能够诱导LSECs中HO-1表达。结论PTE通过诱导血红素氧化酶-1表达减轻小鼠肝窦内皮细胞氧化损伤,保护肝脏免受缺血/再灌注损伤。

Aim To explore the mechanism of the natural phenolic compound pterostilbene(PTE)in the protection of liver ischemic/reperfusion.Methods A total of 40 C57 mice were divided into control group,model group,drug delivery group and treatment group and a 70%liver ischemic/reperfusion(ischemic 60 min)model was established,then primary LSECs were isolated by perfusion and digestion.Hepatic structural disruption was observed by HE staining.The ultrastructure of hepatic sinus endothelial cells was observed by transmission electron microscopy(TEM).The structure of LSECs fenestrae was observed by scanning electron microscopy(SEM).The expression level of heme oxygenase 1(HO-1)in LSECs was detected by Western blot.Results HE staining showed that PTE protected against hepatic ischemic injury.TEM observed that PTE had a protective effect on hepatic sinus endothelial cells,and the number of LSECs fenestrae in the blank control group was larger and the number of fenestrae in the liver I/R model group was reduced.The number of LSECs fenestrae in the liver I/R model group treated with PTE increased compared with the untreated liver I/R model group.Western blot result showed that PTE was able to induce HO-1 expression in LSECs.Conclusions PTE alleviates oxidative damage of endothelial cells in mouse hepatic sinus by inducing HO-1expression,and protects the liver from ischemia/reperfusion injury.