Assimakopoulos Stelios F, Vagianos Constantine E, Charonis Aristides S, Alexandris Ilias H, Spiliopoulou Iris, Thomopoulos Konstantinos C, Nikolopoulou Vassiliki N, Scopa Chrisoula D
Department of Internal Medicine, School of Medicine, University of Patras, Greece.
World J Gastroenterol. 2006 Jun 7;12(21):3410-5. doi: 10.3748/wjg.v12.i21.3410.
To investigate the influence of experimental obstructive jaundice and exogenous bombesin (BBS) and neurotensin (NT) administration on the expression of the tight junction (TJ)-protein claudin-4 in intestinal epithelium of rats.
Forty male Wistar rats were randomly divided into five groups: I = controls, II = sham operated, III = bile duct ligation (BDL), IV = BDL+BBS (30 microg/kg per d), V = BDL+NT (300 microg/kg per d). At the end of the experiment on d 10, endotoxin was measured in portal and aortic blood. Tissue sections of the terminal ileum were examined histologically and immunohistochemically for evaluation of claudin-4 expression in intestinal epithelium.
Obstructive jaundice led to intestinal barrier failure demonstrated by significant portal and aortic endotoxemia. Claudin-4 expression was significantly increased in the upper third of the villi in jaundiced rats and an upregulation of its lateral distribution was noted. Administration of BBS or NT restored claudin-4 expression to the control state and significantly reduced portal and aortic endotoxemia.
Experimental obstructive jaundice increases claudin-4 expression in intestinal epithelium, which may be a key factor contributing to the disruption of the mucosal barrier. Gut regulatory peptides BBS and NT can prevent this alteration and reduce portal and systemic endotoxemia.
研究实验性梗阻性黄疸以及外源性给予蛙皮素（BBS）和神经降压素（NT）对大鼠肠上皮紧密连接（TJ）蛋白claudin-4表达的影响。
40只雄性Wistar大鼠随机分为五组：I组=对照组，II组=假手术组，III组=胆管结扎（BDL）组，IV组=BDL+BBS（每日30微克/千克），V组=BDL+NT（每日300微克/千克）。在实验第10天结束时，检测门静脉和主动脉血中的内毒素。对回肠末端组织切片进行组织学和免疫组织化学检查，以评估肠上皮中claudin-4的表达。
梗阻性黄疸导致肠屏障功能衰竭，表现为门静脉和主动脉内毒素血症显著升高。黄疸大鼠绒毛上三分之一处claudin-4表达显著增加，且其侧向分布上调。给予BBS或NT可使claudin-4表达恢复至对照状态，并显著降低门静脉和主动脉内毒素血症。
实验性梗阻性黄疸可增加肠上皮中claudin-4的表达，这可能是导致黏膜屏障破坏的关键因素。肠道调节肽BBS和NT可预防这种改变，并降低门静脉和全身内毒素血症。
