Herouy Yared, Kahle Birgit, Idzko Marco, Eberth Ingo, Norgauer Johannes, Pannier Felizitas, Rabe Eberhard, Jünger Michael, Bruckner-Tuderman Leena
Dermato-Phlebologische Praxis, D-76530 Baden-Baden, Germany.
Int J Mol Med. 2006 Jul;18(1):215-9.
Tight junctions (TJs) provide a barrier function, inhibiting solute and water flow through the paracellular space. There had been no analysis until now as to how tight junction molecules could be involved in the pathology of patients with chronic venous insufficiency. The aim of the study was to analyse the expression pattern of TJ-molecules occludin (OCLN), claudin-1 (CLDN-1), claudin-3 (CLDN-3) and claudin-5 (CLDN-5) on mRNA and protein level in patients with edema, venous leg ulcers and healthy controls. Biopsy specimens were taken in healthy individuals and in patients before, and four weeks after compression therapy. mRNA-expression was determined by using reverse-transcriptase and polymerase chain reaction (RT-PCR) and the protein-expression was determined by Western blotting from tissue specimens. Quantification performed determining the expression for TJ-molecules displayed diminished expression for CLDN-1 (p<0.01) and CLDN-5 (p<0.01) in patients with chronic venous insufficiency in comparison with healthy controls on mRNA as well as protein level. No statistical differences were detected for OCLN and CLDN-3 between the edema group and healthy controls. There was a significantly elevated expression (p<0.01) on mRNA and protein level between the leg ulcer group and healthy controls for OCLN and CLDN-3. Densitometric evaluation revealed a more significantly elevated expression (p<0.01) for CLDN-1 and CLDN-5 on mRNA and protein level after four weeks of compression therapy in comparison with prior to treatment for the edema as well as the leg ulcer group. Compression therapy tightens the paracellular barrier via elevated expression of specific TJs and prevents thereby the progression of chronic venous insufficiency due to inhibited permeability of fluid into the perivascular tissue.
紧密连接（TJs）具有屏障功能，可抑制溶质和水通过细胞旁间隙流动。迄今为止，尚未有关于紧密连接分子如何参与慢性静脉功能不全患者病理过程的分析。本研究的目的是分析紧密连接分子闭合蛋白（OCLN）、紧密连接蛋白-1（CLDN-1）、紧密连接蛋白-3（CLDN-3）和紧密连接蛋白-5（CLDN-5）在水肿患者、下肢静脉溃疡患者及健康对照者的mRNA和蛋白质水平上的表达模式。在健康个体以及患者接受压迫治疗前和治疗四周后采集活检标本。通过逆转录酶和聚合酶链反应（RT-PCR）测定mRNA表达，通过蛋白质印迹法从组织标本中测定蛋白质表达。定量分析显示，与健康对照相比，慢性静脉功能不全患者CLDN-1（p<0.01）和CLDN-5（p<0.01）在mRNA和蛋白质水平上的表达均降低。水肿组与健康对照组之间，OCLN和CLDN-3未检测到统计学差异。下肢静脉溃疡组与健康对照组相比，OCLN和CLDN-3在mRNA和蛋白质水平上的表达显著升高（p<0.01）。密度测定评估显示，与治疗前相比，水肿组和下肢静脉溃疡组在接受四周压迫治疗后，CLDN-1和CLDN-5在mRNA和蛋白质水平上的表达升高更为显著（p<0.01）。压迫治疗通过提高特定紧密连接的表达来收紧细胞旁屏障，从而由于抑制液体向血管周围组织的渗透而防止慢性静脉功能不全的进展。
