N-乙酰-5-羟色胺对大鼠肝缺血再灌注损伤后细胞凋亡的影响  

Effect of N-acetylserotonin on hepatocyte apoptosis after liver ischemia-reperfusion injury in rats

作　　者：姜政辰[1] 梁翠宏[2] 王海亮[3] 陈悦[1] 郑洁[4] 于树娜[2] 蒋吉英[2] 

机构地区：[1]潍坊医学院 [2]潍坊医学院解剖学教研室,山东省潍坊市261053 [3]潍坊医学院外科学教研室,山东省潍坊市261053 [4]潍坊医学院病理学教研室,山东省潍坊市261053

出　　处：《世界华人消化杂志》2015年第9期1387-1394,共8页World Chinese Journal of Digestology

基　　金：山东省自然科学基金资助项目;Nos.ZR2010HM006;ZR2014HL020;ZR2014HL021;山东省教育厅基金资助项目;No.J11LF14;山东省"泰山学者"建设工程专项基金资助自主项目;山东省医药卫生科技发展计划基金资助项目;No.2014WS0464;潍坊医学院科技创新研究基金资助项目;No.K1301001;潍坊医学院大学生科技创新基金资助项目;No.KX2013001~~

摘　　要：目的:探讨N-乙酰-5-羟色胺(N-acetylserotonin,NAS)对肝缺血再灌注(ischemia-reperfusion,I/R)损伤后细胞凋亡的作用.方法:♂成年未经产SD大鼠,随机分为假手术(Sham)组、I/R组和I/R+NAS组.采用夹闭至肝中叶和左叶肝蒂的分支的方法制作肝I/R模型,冰冻切片,HE染色检测肝细胞形态;RT-PCR和免疫组织化学染色观察激活型Caspase3、Bcl-2和Bax的表达;TUNEL法检测细胞凋亡并计算肝细胞凋亡指数(apoptosis index,AI).结果:(1)HE染色显示,I/R组肝细胞出现明显的水样变性和局灶性坏死,NAS可减轻I/R损伤所引起的肝组织结构的破坏;(2)与Sham组相比,I/R损伤后AI、激活型Caspase3、B c l-2和B a x的表达升高,B c l-2/B a x降低(P<0.01),N A S干预可使A I降低(P<0.01),Caspase3和Bax的表达降低,Bcl-2的表达及Bcl-2/Bax显著升高(P<0.01).结论:NAS可通过提高Bcl-2、降低Bax的表达,抑制Caspase3的激活,减轻肝I/R损伤所致的肝细胞凋亡.AIM： To investigate the effect of N-acetylserotonin（NAS） on hepatocyte apoptosis after liver ischemiareperfusion（I/R） injury in rats. METHODS： Adult male SD rats weighting 200-250 g were used. The afferent vessels of the left and median lobes were occluded by a microvascular bulldog clamp and then reperfused after 60 min with or without NAS. The morphologic changes and hepatocyte apoptosis were evaluated by hematoxylineosin（HE） staining and TUNEL（terminal deoxynucleotidyl transferase d UTP nick end labeling） staining, respectively. The expression of Bcl-2, Bax and activated Caspase3 was evaluated by immunohistochemistry. RESULTS： The hepatocytes exhibited markedballooning hydropic degeneration and focal necrosis in the I/R group. NAS pretreatment rescued the morphological damage. Compared with the sham operation group, the expression of cleaved Caspase3, Bcl-2 and Bax in the liver tissue was increased, and the ratio of Bcl-2/Bax was decreased in the I/R group（P 0.01）. The apoptosis index（AI） and expression of cleaved Caspase3 and Bax were decreased in the NAS intervention group compared with the I/R group（P 0.01）, and the expression of Bcl-2 and Bcl-2/Bax ratio were increased（P 0.01）.CONCLUSION： NAS could attenuate hepatocyte apoptosis after liver I/R injury via mechanisms possibly associated with induction of Bcl-2 protein expression and inhibition of Bax protein expression in hepatocytes.

关 键 词：缺血再灌注损伤 细胞凋亡 N-乙酰-5-羟色胺 肝 大鼠 

分 类 号：R575[医药卫生—消化系统]