摘要
目的观察5-脂氧酶(5-LO)抑制剂咖啡酸对慢性铝负荷所致大鼠肝损伤的保护作用,并初步探讨其可能的机制。方法将SD大鼠分为空白对照组、慢性铝负荷模型组、咖啡酸低剂量组和咖啡酸高剂量组,除空白对照组外,每组大鼠每天灌胃给予葡萄糖酸铝(Al3+200 mg·kg-1·d-1),给药组大鼠在给铝后1周分别灌胃给予2个剂量的咖啡酸,每周5 d,连续20周。建模完成后,用生化法检测大鼠血清中丙氨酸氨基转移酶(ALT),天门冬氨酸氨基转移酶(AST)和碱性磷酸酶(ALP)活性,以及肝组织丙二醛(MDA)含量,超氧化物歧化酶(SOD)活性,采用苏木精-伊红染色法观察大鼠肝脏组织形态学变化,用免疫组织化学法检测大鼠肝组织5-LO蛋白表达情况。结果与空白对照组大鼠比较,慢性铝负荷模型组大鼠血清ALT、AST、ALP活性显著升高,肝组织MDA含量显著增加,SOD活性显著下降,肝细胞出现明显空泡性变、点状坏死、肝细胞排列紊乱,肝组织5-LO在血管周围肝细胞胞浆中表达明显。与铝负荷模型组比较,给予咖啡酸后大鼠肝细胞损伤减轻,血清ALT、AST、ALP活性明显降低,肝组织MDA含量显著减少,SOD活性显著上升,肝组织5-LO表达明显减少。结论咖啡酸能减轻慢性铝负荷所致肝损伤,机制可能与其抑制5-LO表达、减轻氧化应激反应损伤有关。
Objective To study the protective effect and primary mechanism of caffeic acid on liver damage that induced by chronic aluminum overload in rats. Methods The SD rats were divided into 4 groups ： normal control group, chronic a- luminum-overload group, and caffeic acid 10 mg ·kg-1 and 30 mg · kg-1 treated groups. Except the normal control group, the rats were given aluminum gluconate （ Al3· 200 mg · kg-1 ） intragastrically once a day, 5 days a week for 20 weeks. The 5-LO inhibitor caffeic acid （10 mg· kg-1,30 mg·kg-1 ） was intragastrically administered 1 hour after aluminum adminis- tration. The biochemical method was used to detect the alanine aminotransferase （ ALT）, aspartate aminotransferase （AST） and alkaline phosphatase （ALP） activity in rat serum, and the malondialdehyde （MDA） content and superoxide dismutase （SOD） activity in liver. HE staining was used to observe the morphological changes in liver, the 5-LO protein production was detected using the immunohistochemical method. Results Compared with the normal control group, the serum＇ s ALT, AST, and ALP activity of experimental groups were increased significantly. The MDA content was elevated significantly, while the SOD activity of aluminum-overload rats＇ liver was decreased significantly. Liver cells in chronic aluminum-over- load rats showed a significant vacuolar degeneration, necrosis and irregular arrangement. 5-LO protein was highly expressed in aluminum-overload rat liver cells. Compared with that of aluminum-overload group, liver injury in caffeic acid-treated group was significantly improved. Administration of caffeic acid significantly impaired the increase of ALT, AST, and ALP activity, and significantly increased the SOD activity. Caffeic acid also significantly decreased the MDA content and downregulated the 5-LO protein expression in the liver. Conclusions Caffeic acid can alleviate liver injury induced by chronicaluminum overload. The inhibition of 5-LO protein expression and oxidative stress were involved in the protective mechanisms of caffeic acid.
出处
《四川动物》
北大核心
2015年第2期251-255,共5页
Sichuan Journal of Zoology
基金
重庆市卫生局医学科研计划项目(2012-02-047)
重庆市基础与前沿研究计划项目(cstc2013jcyj A10004)
关键词
咖啡酸
铝负荷
肝损伤
5-脂氧酶
氧化应激
caffeic acid
aluminum overload
liver injury
5-1ipoxygenase
oxidative stress
