摘要
背景:Claudin蛋白家族是构成细胞紧密连接的重要分子,其中claudin-2是一种在肝细胞和胆管细胞中高表达的细胞旁通道形成蛋白,具有水分子和阳离子的选择渗透性,在消化和泌尿系统中发挥至关重要的生理调控作用。目的:探讨claudin-2在胆固醇结石形成和胆汁分泌过程中的作用及其机制。方法:收集claudin-2基因敲除(Cldn-2-/-)小鼠和野生型(Cldn-2+/+)小鼠的肝脏和胆囊组织,以蛋白质印迹法检测claudin蛋白家族的表达,HE染色、免疫荧光染色和电镜观察敲除claudin-2基因对肝脏和胆囊组织结构的影响。并分析claudin-2蛋白对胆汁成分和流速的调控作用。结果:Claudin家族蛋白在Cldn-2+/+小鼠肝脏和胆囊组织中高表达。与Cldn-2+/+小鼠相比,Cldn-2-/-小鼠肝脏和胆囊组织结构无明显差异,胆汁流速明显降低(P<0.05),胆汁浓度明显增加(P<0.05),肝脏和胆囊胆汁中的胆汁酸、胆固醇、胆红素、磷脂含量显著增加(P<0.05)。结论:Claudin-2蛋白通过调控胆汁成分和细胞紧密连接中的水分子旁分泌过程,影响胆汁的形成,这一过程的失调显著增加了小鼠对胆固醇结石相关疾病的易感性。
Background:Claudin protein family is an important component for construction of tight cell junction.Claudin-2 is a forming protein of paracellular channel and is highly expressed in hepatocytes and bile duct cells,which has selective permeability of water molecules and cations.Claudin-2 plays a vital role in the physiological regulation of digestive and urinary systems.Aims:To investigate the role and mechanism of claudin-2 in formation of cholesterol gallstone and bile secretion.Methods:Liver and gallbladder tissues from claudin-2 knockout(Cldn-2-/-)and wild type(Cldn-2+/+)mice were collected.Expressions of claudin family protein were determined by Western blotting.HE staining,immunofluorescence staining,electron microscope were used to analyze the effect of claudin-2 gene knockout on liver and gallbladder tissue structure.Regulatory roles of claudin-2 in bile component and flow were analyzed.Results:Claudin family proteins were highly expressed in liver and gallbladder tissue in Cldn-2+/+mice.No significant difference in structure of liver and gallbladder tissue was found between Cldn-2-/-mice and Cldn-2+/+mice.Compared with Cldn-2+/+mice,bile flow rate was significantly decreased(P<0.05),concentration of bile was significantly increased(P<0.05),and contents of bile acid,cholesterol,bilirubin,phospholipid in liver and gallbladder bile were significantly increased in Cldn-2-/-mice(P<0.05).Conclusions:Claudin-2 regulates paracellular water flow which is required for proper regulation of bile composition and flow.Dysregulation of this process increases the susceptibility to cholesterol gallstone related diseases in mice.
作者
陈跃
冯亚东
赵向阳
CHEN Yue;FENG Yadong;ZHAO Xiangyang(Department of Gastroenterology,Nanjing Lishui People’s Hospital(Zhongda Hospital Lishui Branch Hospital,Southeast University),Nanjing,211200;Department of Gastroenterology, Zhongda Hospital, Southeast University, Nanjing)
出处
《胃肠病学》
2019年第11期667-670,共4页
Chinese Journal of Gastroenterology
基金
南京市卫生科技发展专项资金项目(YKK18215)
