Bruck R, Hershkoviz R, Lider O, Shirin H, Aeed H, Halpern Z
Department of Gastroenterology, Wolfson Medical Center, Holon, Israel.
Isr Med Assoc J. 2000 Jul;2 Suppl:74-80.
In chronic viral hepatitis, autoimmune hepatitis, and some chronic cholestatic liver diseases, T lymphocytes serve as effector cells of the immunostimulatory processes. Cellular interactions of immune cells with extracellular matrix components are regulated primarily via the beta 1 subfamily of integrin receptors. The target epitope of several such integrin receptors is the Arg-Gly-Asp sequence, a cell adhesion motif shared by several matrix-associated adhesive glycoproteins. We review the use of synthetic non-peptidic analogs of RGD in the prevention of immune-mediated, concanavalin A-induced liver damage in mice and in inhibiting the development of liver cirrhosis in rats. The Con A-induced elevation of serum transaminases and tumor necrosis factor-alpha and the infiltration of liver tissue by inflammatory cells were inhibited by pretreatment of the mice with the synthetic RGD mimetics. In rats, the progression of thioacetamide-induced liver cirrhosis was markedly inhibited by the co-administration of the RGD mimetic SF-6,5. The compounds described here may be examined therapeutically for pathological conditions in the liver, manifested as necro-inflammation and fibrosis.
在慢性病毒性肝炎、自身免疫性肝炎以及一些慢性胆汁淤积性肝病中，T淋巴细胞作为免疫刺激过程的效应细胞。免疫细胞与细胞外基质成分的细胞间相互作用主要通过整合素受体的β1亚家族进行调节。几种此类整合素受体的靶表位是精氨酸-甘氨酸-天冬氨酸序列，这是几种与基质相关的黏附糖蛋白共有的细胞黏附基序。我们综述了RGD的合成非肽类似物在预防小鼠免疫介导的、伴刀豆球蛋白A诱导的肝损伤以及抑制大鼠肝硬化发展方面的应用。用合成的RGD模拟物对小鼠进行预处理，可抑制伴刀豆球蛋白A诱导的血清转氨酶和肿瘤坏死因子-α升高以及炎性细胞对肝组织的浸润。在大鼠中，RGD模拟物SF-6,5的共同给药显著抑制了硫代乙酰胺诱导的肝硬化进程。本文所述的化合物可针对表现为坏死性炎症和纤维化的肝脏病理状况进行治疗性研究。
