甲基阿魏酸对CCl4诱导肝纤维化大鼠肝脏氧化应激损伤和细胞外基质积聚的影响

摘要

Objective To study the effects of methyl ferulic acid on liver oxidative stress injury and extracellular ma-trix accumulation in rats with liver fibrosis induced by carbon tetrachloride (CCl 4 ). Methods Sixty male SD rats were randomly divided into the normal group,model group,high-dose methyl ferulic acid group (20 mg/ kg),medium-dose methyl ferulic acid group (10 mg/ kg),and low-dose methyl ferulic acid group (5 mg/ kg). CCl 4 was used to replicate the liver fibrosis model,Methyl ferulic acid high-,medium-,and low-dose group were given the appropriate dose of methyl fer-ulic acid by gavage. Hepatic tissues were stained with HE and the pathological changes were observed. Biochemical analy-sis was used to detect the levels of alanine aminotransferase (ALT),aspartate aminotransferase (AST),catalase (CAT), glutathione peroxidase (GSH-Px),superoxide dismutase (SOD),and propane aldehyde (MDA). The content of serum precollagen Ⅲ (PCⅢ),type Ⅳ collagen (Ⅳ-C),hyaluronic acid (HA),and laminin (LN)was measured by enzyme-linked immunosorbent assay (ELISA). The expression of α-SMA,PCI mRNA and protein in liver tissues was detected by reverse transcription-polymerase chain reaction (RT-PCR)and Western blotting. Results Compared with the normal group,the levels of ALT,AST,MDA,PCⅢ,Ⅳ-C,HA,and LN of the model group increased significantly (all P <0. 05);the levels of CAT,GSH-Px,and SOD decreased significantly (P < 0. 05);liver and spleen index significantly in-creased (P < 0. 05);significant characteristics of liver fibrosis were found;the mRNA and protein expression of α-SMA and PCI in the liver tissues were significantly enhanced (both P < 0. 01). The levels of ALT,AST,MDA,PCⅢ,Ⅳ-C, HA,and LN decreased (all P < 0. 01),and the activities of CAT,GSH-Px,and SOD increased (all P < 0. 05),and the liver and spleen index significantly decreased (P < 0. 05),and the mRNA and protein expression of α-SMA and PCI in the liver tissues decreased in the high-,medium-,and low-dose groups as compared with those of the model group (all P <0. 01). Conclusions Methyl ferulic acid can effectively improve the liver oxidative stress injury,reduce the accumulation of extracellular matrix,and alleviate the degree of hepatic fibrosis of rats with hepatic fibrosis induced by CCl%目的 探讨甲基阿魏酸对四氯化碳(CCl 4)诱导肝纤维化大鼠肝脏氧化应激损伤和细胞外基质积聚的影响.方法 将60只雄性成年SD大鼠随机分为正常组、模型组、甲基阿魏酸高、中、低剂量组,用CCl 4复制肝纤维化模型,甲基阿魏酸高、中、低剂量组分别给予20、10、5 mg/kg甲基阿魏酸灌胃.生化分析法测定血清ALT、AST及肝组织中丙二醛(MDA)、超氧化物歧化酶(SOD)、谷胱甘肽过氧化物酶(GSH-Px)、过氧化氢酶(CAT)水平.ELISA法检测血清Ⅲ型前胶原(PCⅢ)、Ⅳ型胶原(Ⅳ-C)、透明质酸(HA)、层黏连蛋白(LN)含量.RT-PCR法和Western blotting法分别检测肝组织中α-SMA、PCⅠmRNA及蛋白表达.结果 与正常组比较,模型组大鼠ALT、AST、MDA及PCⅢ、Ⅳ-C、HA、LN含量升高(P均<0.01),CAT、GSH-Px及SOD活性降低(P均<0.01),肝脾指数升高(P<0.01),有明显的肝纤维化特征,肝组织中α-SMA和PCⅠmRNA及蛋白表达增强(P均<0.01).而甲基阿魏酸高、中、低剂量组与模型组比较,ALT、AST、MDA及PCⅢ、Ⅳ-C、HA、LN降低(P均<0.01),CAT、GSH-Px及SOD活性升高(P均<0.01),肝脾指数降低(P<0.01),肝组织中α-SMA、PCⅠmRNA及蛋白表达降低(P均<0.01).结果 甲基阿魏酸可有效改善CCl 4诱导肝纤维化大鼠的肝脏氧化应激损伤,减少细胞外基质的积聚,减轻肝纤维化程度.