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该文探讨了脂氧素A4受体激动剂BML-111[5(S),6(R),7-trihydroxyheptanoic acid methyl ester]对四氯化碳(carbon tetrachloride,CCl4)诱导的大鼠肝纤维化模型氧化和抗氧化平衡的影响。40只SD(Sprague-Dawley)大鼠皮下注射40%CCl4以建立肝纤维化模型,干预处理为在不同时间段皮下注射1 mg/kg BML-111。经不同的方式处理过的40只SD大鼠被分为4组,分别为对照组、CCl4组、治疗组和预防组。通过观察肝脏表面的颜色、光滑度及结节确定大鼠肝纤维化程度;通过病理组织切片HE(hematoxylin-eosin)染色对大鼠肝脏损伤和炎症细胞浸润情况进行评估;通过检测肝组织匀浆中丙氨酸转氨酶(alanine transaminase,ALT)和天冬氨酸转氨酶(aspartate transaminase,AST)活性进行评价大鼠肝功能情况;通过检测肝组织中脂质氧化产物丙二醛(malondialdehyde,MDA)含量、抗氧化酶如谷胱甘肽过氧化物酶(glutathione peroxidase,GSH-Px)、超氧化物歧化酶(superoxide dismutase,SOD)和过氧化氢酶(catalase,CAT)活性以及肝组织中总抗氧化能力(total antioxidative capacity,T-AOC)对大鼠体内氧化/抗氧化平衡状态进行评价。结果显示,CCl4组大鼠肝脏颜色明显偏黄,表面失去光滑,结节化程度最严重;BML-111预防或治疗后,其症状明显改善。BML-111可以抑制CCl4诱导的大鼠肝脏损伤和炎症细胞浸润。CCl4组肝组织匀浆液中ALT和AST活性明显降低;BML-111能够提高ALT和AST的活性(P<0.05)。CCl4组MDA含量明显升高,而GSHPx、SOD和CAT的活性降低,总抗氧化能力T-AOC下降。BML-111预防或治疗处理后,MDA含量明显下降(P<0.05),T-AOC增强(P<0.05),GSH-Px、CAT和SOD的活性均明显回升(P<0.05)。由此可知,BML-111可以抑制CCl4诱导的大鼠肝纤维化,此效应与其调节肝组织的氧化/抗氧化平衡相关。
This article explored the effect of lipoxygenin A4 receptor agonist BML-111 [5 (S), 6 (R), 7-trihydroxyheptanoic acid methyl ester on rat liver fibrosis induced by carbon tetrachloride (CCl4) Effects of oxidative and antioxidative balance on the model. Forty SD rats (Sprague-Dawley) were subcutaneously injected with 40% CCl4 to establish a liver fibrosis model, and the intervention was subcutaneous injection of 1 mg / kg BML-111 at different time points. Forty Sprague-Dawley rats treated in different ways were divided into four groups: control group, CCl4 group, treatment group and prevention group. The degree of liver fibrosis was determined by observing the color, smoothness and nodules of the liver surface. Hepatic injury and inflammatory cell infiltration were evaluated by hematoxylin-eosin (HE) staining. The liver tissue homogenate Alanine transaminase (ALT) and aspartate transaminase (AST) activity in rats were evaluated for liver function. The contents of malondialdehyde (MDA) , Antioxidant enzymes such as glutathione peroxidase (GSH-Px), superoxide dismutase (SOD) and catalase (CAT) activity, and total hepatic The total antioxidant capacity (T-AOC) was used to evaluate the oxidative / antioxidant balance in rats. The results showed that the color of liver in CCl4 group was obviously yellow, the surface was not smooth and the degree of nodularity was the most serious. After the prevention or treatment of BML-111, the symptoms were obviously improved. BML-111 can inhibit CCl4-induced liver injury and inflammatory cell infiltration in rats. The activities of ALT and AST in CCl4 group were significantly decreased. BML-111 increased the activity of ALT and AST (P <0.05). The content of MDA in CCl4 group increased obviously while the activities of GSHPx, SOD and CAT decreased while the total antioxidant capacity T-AOC decreased. After treatment with BML-111, the content of MDA was significantly decreased (P <0.05), T-AOC was increased (P <0.05), and the activities of GSH-Px, CAT and SOD were significantly increased (P <0.05). Thus, BML-111 can inhibit CCl4-induced hepatic fibrosis in rats, the effect of its regulation of liver tissue oxidation / antioxidant balance.