欧当归内酯A对实验性纤维化肝脏NO及内皮细胞功能的影响

Effect of Levistilide A on NO and Endothelial Cell Function in Experimental Fibrosis

目的:探讨欧当归内酯A调节纤维化肝脏NO释放的抗肝纤维化作用机制。方法:40只Wistar大鼠随机分为正常组、模型组、欧当归内酯A 3 mg/kg组、欧当归内酯A 6 mg/kg组,每组10只。以四氯化碳(CCl4)与高脂低蛋白饮食复合因素诱导肝纤维化模型,连续6周。药物观察组于造模第4周腹腔注射给药至结束。观察肝组织炎性反应及胶原沉积、eNOS表达及MDA、SOD、NO、NOS水平。体外以800μmol/L氯化钴作用于SK-HEP-1细胞24 h诱导细胞缺氧损伤,药物处理后观察细胞活力、vWF表达、上清及胞内NO水平。结果:与模型组比较,欧当归内酯A各组肝细胞变性和炎性反应坏死有所减轻,纤维化改善;高剂量组SOD和MDA显著改善,NO和NOS降低,eNOS阳性表达下降(P<0.05)。体外实验显示,药物干预后细胞活力得到改善,vWF平均荧光强度减弱,NO释放显著改善(P<0.05)。结论:欧当归内酯A具有抗肝纤维化的作用,其机制可能与抗脂质过氧化损伤,改善内皮细胞功能,调节NO释放有关。

Objective:To explore the effects of levistilide A on anti-hepatic fibrosis mechanism of regulating the release of NO from fibrotic liver.Methods:A total of 40 Wistar rats were randomly divided a control group,a model group,a levistilide A 3 mg/kg group and a levistilide 6 mg/kg group,with 10 rats in each group.The liver fibrosis model was induced by a combination of carbon tetrachloride(CCl4)and a high-fat and low-protein diet for 6 consecutive weeks.The drug treatment group was given intraperitoneal injection to the end on the 4th week of modeling.Liver tissue inflammatory reaction and collagen deposition,eNOS expression and MDA,SOD,NO,NOS levels were observed.In vitro,800μmol/L cobalt chloride was applied to SK-HEP-1 cells for 24 h to induce cell hypoxia.After drug treatment,cell viability,vWF expression,supernatant and intracellular NO levels were observed.Results:Compared with those in the model group,the degeneration and inflammatory necrosis of Levistilide A in each group were reduced,and the fibrosis was improved;the high-dose group SOD and MDA significantly improved,NO and NOS decreased,and the positive expression of eNOS decreased(P<0.05).In vitro experiments showed that cell viability was improved after drug intervention,the average fluorescence intensity of vWF was weakened,and the release of NO was significantly improved(P<0.05).Conclusion:Levistilide A can inhibit liver fibrosis,the mechanism may be related to Levistilide A,anti-lipid peroxidation,and regulate the release of NO.