海兔素对慢性酒精性肝损伤大鼠肝超微结构及NO和iNOS的影响  

Effects of Aplysin on ultrastructure,NO and iNOS in rats with chronic alcoholic liver injury

作　　者：戈娜[1,2] 梁惠[1] 刘颖[3] 宫安静[4] 王文成[1] 

机构地区：[1]青岛大学公共卫生学院营养研究所,山东青岛266021 [2]内蒙古科技大学包头医学院营养与食品卫生学教研室,内蒙古包头014060 [3]青岛大学基础学院细胞与分子生物学实验室,山东青岛266071 [4]青岛大学附属医院脑外科,山东青岛266003

出　　处：《中国海洋药物》2014年第3期63-68,共6页Chinese Journal of Marine Drugs

基　　金：国家自然科学基金(31171671);"十二五"农村领域国家科技计划课题(2012BAD33B01-2)资助

摘　　要：目的研究海兔素(Aplysin)对酒精所致慢性肝损伤大鼠一氧化氮(NO)水平和诱导型一氧化氮合酶(iNOS)活性及表达的影响,探讨海兔素对酒精性肝损伤的保护作用。方法雄性Wistar大鼠50只,按体质量随机分为5组,每组10只。用电镜观察肝脏超微结构变化;用比色法检测血清中转氨酶和NOS活性以及NO含量;采用Western blotting检测大鼠肝脏中iNOS蛋白表达水平的变化。结果透射电镜下,各剂量海兔素组肝线粒体、内质网结构均较模型组明显改善。与酒精模型组相比,不同剂量的海兔素组血清ALT、AST、TNOS、iNOS活性以及NO含量均有不同程度地降低,且成剂量依赖关系。中、高剂量海兔素可明显抑制大鼠肝组织中iNOS的蛋白表达(P<0.05)。结论iNOS和NO在慢性酒精性肝损伤中起促进作用,海兔素可能通过抑制体内iNOS活性,下调了体内iNOS蛋白表达,减少NO生成,最终达到保肝的作用。Objective To explore the protective effects of Aplysin on level of nitric oxide, activity and pro- tein level of nitric oxide synthase in rats with chronic alcoholic liver injury. Methods Male Wistar rats （n= 10 for each group） were randomly divided into five groups. Apart from the rats in the normal control group, the other animals were initially administered orally with 50% （v/v） ethanol 8ml · kg^-1 day^-1 for 2 weeks following by an increasing intake of ethanol up to 12ml · kg^-1 day^-1 for the remaining 4 weeks. Meanwhile the alcohol＋Aplysin-treated groups were administered daily Aplysin doses （i. e. ,low, medium, and high） of 50, 100, 150mg ·kg^-1 day 1, respectively, by gavage for 42 consecutive days; the other groups received an equal volume of vehicle as a control. Ultrastructural changes in the livers of rats were observed by transmission electron microscope （TEM）. The activities of alanine ami- notransferase （ALT）, aspartate aminotransferase （AST）, nitric oxide synthase （NOS） and nitric oxide （NO） content in serum were determined by colorimetric method. The protein expression of iNOS in liver was detected by Western blotting. Results Hepatic ultrastructure lesions were reduced in different doses Aplysin groups compared with alcohol model group. Compared with the control group, the activi- ties of serum aminopherase and NOS, NO level were significantly increased in the alcohol group （P〈 0.05）. Administration of Aplysin significantly decreased the levels of serum aminopherase , NOS activ- ities and NO levels in a dose-dependent manner; however, there were no significant differences between the Aplysin treatment groups （P〉0. 05）. In addition, medium-, and high-dose Aplysin could significantly inhibit the expression of iNOS（P〈0. 05）. Conclusion NO and iNOS are involved in the chronic liver injury induced by alcohol. However, Aplysin has protective effect on chronic alcoholic liver injury, and the mechanism may be associated with inhibition of iNOS activ

关 键 词：海兔素 酒精性肝损伤 一氧化氮 一氧化氮合酶 超微结构 

分 类 号：R965[医药卫生—药理学]