D'Orléans-Juste P, Chakir M, Berthiaume N, Plante G E
Département de pharmacologie, Faculté de médecine, Université de Sherbrooke, Québec, Canada.
Therapie. 1997 Sep-Oct;52(5):407-13.
Among numerous complications associated with diabetes, the alterations of the normal properties of various microcirculation circuits lead to important dysfunctions which may contribute to target organ damage. As the endothelium plays a crucial role in the microcirculatory circuits, it is suggested that diabetes may influence both the physical and endocrine properties of that cell layer. In 1995, we reported an important increase in plasma extravasation in a model of diabetes in rats treated with streptozotocin. The increase of plasma extravasation was particularly significant in the pulmonary, skin and splanchnic areas. In that particular study, it was of interest that inhibitors of neutral endopeptidases, such as thiorphan, phosphoramidon and SQ 28,603 (specific inhibitor of the recombinant neutral endopeptidases2) corrected almost completely the increase of plasma extravasation induced by diabetes when compared with control rats. It is also worthy of note that the three above-mentioned inhibitors failed to normalize in any case the hyperglycaemia associated with the diabetes in these animals. The present document is a summary synthesis of the putative role of neutral endopeptidases and of the beneficial effects of the inhibitors of these enzymes in diabetes-induced plasma extravasation in the rat.
在与糖尿病相关的众多并发症中，各种微循环回路正常特性的改变会导致重要功能障碍，这可能促使靶器官损伤。由于内皮细胞在微循环回路中起关键作用，有人提出糖尿病可能会影响该细胞层的物理和内分泌特性。1995年，我们报道在用链脲佐菌素治疗的糖尿病大鼠模型中，血浆外渗显著增加。血浆外渗的增加在肺、皮肤和内脏区域尤为明显。在该特定研究中，有趣的是，与对照大鼠相比，中性内肽酶抑制剂，如硫丙酰胺、磷酰胺脒和SQ 28,603（重组中性内肽酶2的特异性抑制剂）几乎完全纠正了糖尿病诱导的血浆外渗增加。同样值得注意的是，上述三种抑制剂在任何情况下都未能使这些动物与糖尿病相关的高血糖正常化。本文是关于中性内肽酶的假定作用以及这些酶的抑制剂对糖尿病诱导的大鼠血浆外渗的有益作用的总结综述。
