Sanyal A J, Contos M J, Yager D, Zhu Y N, Willey A, Graham M F
Division of Gastroenterology, Medical College of Virginia, Virginia Commonwealth University, Richmond 23298-0341, USA.
Hepatology. 1998 Jul;28(1):22-32. doi: 10.1002/hep.510280105.
The clinical utility of transjugular intrahepatic portasystemic shunts (TIPS) is frequently complicated by the ingrowth of tissue into the stent lumen, causing stent stenosis. These studies were undertaken to define the cellular and matrix components of the pseudointima, define the phenotype and function of the mesenchymal cells in the pseudointima and maintain them in culture, and to study the differences between stenotic and nonstenosed stents. A total of 35 stents were evaluated. TIPS pseudointima were examined histologically, by immunohistochemistry and in situ hybridization to determine the cellular and connective tissue constituents. Mesenchymal cells were grown from tissue within the TIPS and around it, and their phenotype was studied and compared with control smooth muscle cells and fibroblasts. Masson's trichrome staining of histological sections demonstrated that TIPS tissue was composed of collagen and palisades of mesenchymal cells and was lined by an endothelium. Immunostaining demonstrated strong and uniform alpha-smooth muscle staining in TIPS mesenchymal cells and peri-TIPS cells. Type I procollagen mRNA expression was demonstrated in mesenchymal cells in and around the stent by in situ hybridization. TIPS mesenchymal cells secreted less radiolabeled fibronectin, and far more type III, relative to type I, collagen compared with peri-TIPS cells. TIPS cells also expressed high levels of type III procollagen mRNA compared with peri-TIPS cells. There was no difference between stenotic stents and nonstenosed stents with respect to clinical features, time from stenting, gross morphology, histology, presence of bile fistulae, and cell phenotype. However, smooth muscle cells (SMC) from stenotic stents demonstrated both greater cell proliferation and collagen I and III secretion compared with those from nonstenosed stents. These data demonstrate that TIPS stenosis results from an accumulation of collagen and proliferation of SMC within the stent lumen.
经颈静脉肝内门体分流术（TIPS）的临床应用常因组织长入支架管腔而变得复杂，导致支架狭窄。进行这些研究的目的是确定假内膜的细胞和基质成分，明确假内膜中间充质细胞的表型和功能并使其在培养中得以维持，以及研究狭窄支架与非狭窄支架之间的差异。共评估了35个支架。通过组织学、免疫组织化学和原位杂交对TIPS假内膜进行检查，以确定细胞和结缔组织成分。从TIPS及其周围组织中培养间充质细胞，并研究其表型，与对照平滑肌细胞和成纤维细胞进行比较。组织学切片的Masson三色染色显示，TIPS组织由胶原蛋白和间充质细胞的栅栏组成，并衬有内皮。免疫染色显示TIPS间充质细胞和TIPS周围细胞中有强烈且均匀的α平滑肌染色。通过原位杂交在支架内及其周围的间充质细胞中证实了I型前胶原mRNA的表达。与TIPS周围细胞相比，TIPS间充质细胞分泌的放射性标记纤连蛋白较少，而III型胶原蛋白相对于I型胶原蛋白则多得多。与TIPS周围细胞相比，TIPS细胞还高表达III型前胶原mRNA。在临床特征、支架置入时间、大体形态、组织学检查、胆瘘的存在以及细胞表型方面，狭窄支架与非狭窄支架之间没有差异。然而，与非狭窄支架相比，狭窄支架的平滑肌细胞（SMC）表现出更强的细胞增殖以及I型和III型胶原蛋白分泌。这些数据表明，TIPS狭窄是由支架管腔内胶原蛋白的积累和SMC的增殖所致。
