脂氧素A_4受体激动剂BML-111对大鼠肝纤维化模型氧化/抗氧化平衡的影响  

BML-111, A Lipoxin A_4 Receptor Agonist, Regulated the Balance of Oxidation and Antioxidation in Rat Model with Hepatic Fibrosis

作　　者：余忠建[1,2] 胡泉东 徐方云[3] 黄永红[3] 朱俊[3] 周晓燕[3] 

机构地区：[1]南昌大学药学院药理学教研室,南昌330006 [2]江西省肿瘤医院,南昌330006 [3]南昌大学基础医学院病理生理系,南昌330006

出　　处：《中国细胞生物学学报》2016年第10期1208-1213,共6页Chinese Journal of Cell Biology

基　　金：国家自然科学基金(批准号:81100299;81460126)资助的课题~~

摘　　要：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。In order to confirm the effect of BML- 111, a lipoxin A4 receptor agonist, in regulating the balance of oxidation and antioxidation in CCh-induced experimental hepatic fibrosis, forty Sprague-Dawley （SD） rats were used to build the model of hepatic fibrosis through hypodermic injection of 40% CCl4. And 1 mg/kg BML- 111 wasadministrated via subcutaneous for prevention and treatment. These SD rats were respectively divided into 4 groups via treating with different ways： control group, CC14 group, treatment group and prevention group. The severity of hepatic fibrosis was defined by observing the change in color, surface glossy and the extent of nodule in rat liver. The degree of hepatic injury and inflammatory infiltration was assessed by hematoxylin-eosin （HE） staining for the hepatic tissue sections. The liver function was evaluated by detecting the activities of alanine transaminase （ALT） and aspartate transaminase （AST） in hepatic homogenate. The balance of oxidation and antioxidation was evaluated by detecting the content of malondialdehyde （MDA）, the activities of antioxidant enzyme, including GSH-Px, superoxide dismutase （SOD） and catalase （CAT）, and the total antioxidative capacity （T-AOC）. Through the above experiments, several results were found. When compared to the control group, the livers of CC14 treated rats looked obviously slant yellow, lost surface glossy, and performed lots of nodules, which could be improved by BML-111, both in the prevention and the treatment groups. BML-111 could inhibit CC14-induced hepatic injury and inflammatory cell infiltration in rats. CC14 treated rats performed obviously lower activity of AST and ALT in hepatic homogenate, which was reversed when BML-111 was injected （P〈0.05）. BML-111, both in the prevention and the treatment groups, the content of CC14-induced MDA was decreased, but the level of T-AOC and the activities of SOD, GSH-Px and CAT were all increased. The results showed that BML-111 could inhibit CC14- induced experime

关 键 词：脂氧素 肝纤维化 肝功能 氧化 抗氧化 

分 类 号：R575.2[医药卫生—消化系统] R-332[医药卫生—内科学]