木犀草素对四氯化碳致大鼠肝纤维化的保护作用及其机制研究

Preventive effect of luteolin on rat hepatic fibrosis induced by carbon tetrachloride and its mechanism

目的观察木犀草素对四氯化碳(CC l4)致大鼠肝纤维化的保护作用。方法用CC l4复制大鼠中毒性肝纤维化模型,观察木犀草素对大鼠血清中透明质酸(HA)、层黏蛋白(LN)、丙氨酸氨基转移酶(ALT/GPT)、天冬氨酸氨基转移酶(AST/GOT)、总蛋白(TP)、白蛋白(A lb)、肝组织病理学及超氧化物歧化酶(SOD)、丙二醛(MDA)、羟脯氨酸(Hyp)的变化;MTT比色法检测木犀草素对大鼠肝星状细胞(HSC)和人肝星状细胞(Lx-2)的增殖的影响。结果与模型组比较,木犀草素给药组血清学指标(HA、LN)明显降低(P<0.05),ALT、AST减少,TP、A lb升高,病理组织学检查明显改善,肝组织内SOD升高,MDA、Hyp降低,并对HSC、Lx-2细胞的增殖有抑制作用(P<0.05)。结论木犀草素对CC l4致大鼠肝纤维有较好的保护作用,其机制可能与抑制肝内胶原合成、降低自由基生成、减轻脂质过氧化及抑制HSC增殖活化有关。

Purpose To investigate the protective effect of luteolin on CCl4-induced hepatic fibrosis in rats.Methods Hepatic fibrosis models were induced by subcutaneous injection of CCl4 in rats.At the end of the experiment the rats were killed.The level of serum hyaluronic acid（HA）,laminin（LN）,alanine aminotransferase（ALT）,aspartate aminotransferase（AST）,total protein（TP）,albumi（Alb）were assayed,and hematoxylin and eosin（HE）staining was used to examine the changes in liver histopathology,and hepatic tissue activity of superoxide dismutase（SOD）,and hepatic tissue contents of malondialdehyde（MDA）,and hydroxyproline（Hyp）were determined too.Hepatic stellate cells（HSC）proliferation was evaluated by MTT assay.Results Luteolin treatment groups compared with model control group：the levels of HA,LN in serum were lowered obviously（P〈0.05）,also it decreased the serum levels of ALT,AST and the contents of Hyp,MDA in liver tissue,while the levels of SOD and Alb were increased,the hepatic fibrosis of rats was improved obviously after prevention and luteolin can significantly inhibited hepatic stellate cells proliferation（P〈0.05）.Conclusion Luteolin has protective effect on experimental hepatic fibrosis formation.It was suggested that the possible mechanisms were associated with inhibiting fibrogenesis and fibrosis accumulation,decreasing lipid peroxidation,inhibiting HSC activation and proliferation.