水通道蛋白3、8和9的异常亚细胞分布参与大鼠酒精性肝病的发病  

Disrupted subcellular distribution of aquaporin-3,8 and 9 promoted rat alcoholic liver disease

作　　者：李静 赵广西 孙剑勇 LI Jing;ZHAO Guang-xi;SUN Jian-yong(Department of Gastroenterology^Zhongshan Hospital,Fudan University,Shanghai,China))

机构地区：[1]复旦大学附属中山医院消化内科,上海200032

出　　处：《复旦学报（医学版）》2018年第2期177-184,共8页Fudan University Journal of Medical Sciences

基　　金：上海市自然科学基金(13ZR1406700;13DZ1930908)~~

摘　　要：目的研究水通道蛋白(aquaporin,AQP)3、8和9在大鼠酒精性肝病模型中的表达和亚细胞分布的情况。方法将18只SPF级雄性SD大鼠随机分为3组:正常对照组,配对对照组和酒精造模组,每组各6只,分别给予正常啮齿类固体饲料、配对液体饲料和含酒精的液体饲料,喂养6周。通过免疫组化染色、Western blot、实时荧光定量PCR和免疫电镜等方法研究大鼠酒精性肝病动物模型中AQP3、8和9的表达水平及亚细胞分布情况。结果 AQP8、AQP9分布于毛细胆管膜、线粒体内膜等亚细胞结构。酒精摄入可以使大鼠肝脏细胞膜AQP8、AQP9的表达增加;减少AQP8在肝细胞毛细胆管膜和线粒体内膜上的分布并且增加AQP9在肝细胞毛细胆管膜上的分布;增加回肠AQP3和AQP8的膜浆表达比;而在结肠,慢性酒精摄入使AQP8和AQP9的膜浆表达比均下降。结论 AQP3、AQP8和AQP9在大鼠酒精性肝病模型中亚细胞分布异常可能参与酒精性肝病的发病过程。Objective To study the expression profile and subcellular distribution of aquaporin(AQP)3.8 and 9 in SD rat alcoholic liver disease(ALD)models.Methods Eighteen male SPF SD rats were randomized into three groups,which received different treatments for 6 weeks;normal rodent chow-fed group(NC)rats were allowed to consume normal food and water ad libitum ethanolfed group(EtOH)rats and pair-fed group(PF)rats were fed an ethanol-containing Lieber-DeCarli liquid diet and a pair-fed isocaloric high-fat non-ethanol-containing Lieber-DeCarli liquid diet,respectively.We used immunohistochemistry assay,immunoblot,quantitative real-time PCR,and immunoelectron microscopy to determine the expression and subcellular distribution of AQP3,AQP8 and AQP9.Results Our result showed that AQP8 and AQP9 were distributed in bile canaliculus membrane,inner mitochondrial membrane and other subcellular structures in rat hepatocytes.After chronic alcohol intake>AQP8 and AQP9 membranous expression in liver were reduced;in hepatocytes,labeling density of AQP8 in bile canaliculus membrane and inner mitochondrial membrane were downregulated while labeling density of AQP9 in bile canaliculus membrane was increased.The membranous/cytoplasmic expression ratio of AQP3 and AQP8 in ileum were both upregulated;the membranous/cytoplasmic expression ratio of AQP8 and AQP9 in colon were downregulated.In conclusion,our study showed that chronic alcohol intake altered the expression and subcellular distribution of AQP3,AQP8 and AQP9.Conclusions Our study suggested that disordered subcellular distribution of AQP3,8 and 9 participate in the development of ALD.

关 键 词：水通道蛋白 酒精性肝病 亚细胞分布 大鼠 

分 类 号：R575[医药卫生—消化系统]