Cooper M E, Cao Z, Rumble J R, Jandeleit K, Allen T J, Gilbert R E
Department of Medicine, University of Melbourne, Austin & Repatriation Medical Centre, Heidelberg, Victoria, Australia.
Metabolism. 1998 Dec;47(12 Suppl 1):24-7. doi: 10.1016/s0026-0495(98)90367-5.
Vascular disease is now the major cause of morbidity and mortality in the diabetic population. Our group explored the vascular changes associated with experimental diabetes and examined whether these changes can be ameliorated by angiotensin-converting enzyme (ACE) inhibition. The ACE inhibitor perindopril (PE) was administered to streptozotocin-induced diabetic rats for 24 weeks. At death, mesenteric vessels were perfused in vivo followed by assessment of the vascular architecture by quantitative histomorphometry. In a subgroup of animals, RNA was extracted from the mesenteric vasculature for assessment of gene expression of the prosclerotic cytokine, transforming growth factor beta 1 (TGFbeta1), and the matrix protein, type IV collagen. Diabetes was associated with smooth muscle hypertrophy and extracellular matrix (ECM) accumulation. ECM accumulation, particularly collagen deposition, was observed in the medial and adventitial layers. ACE inhibition prevented mesenteric vascular hypertrophy after 24 weeks of diabetes. In addition, overexpression of TGFbeta1 in the vessels of diabetic animals was prevented by PE treatment. Similarly, type IV collagen mRNA levels were increased in diabetic vessels, and this overexpression was also prevented by PE therapy. In summary, ACE inhibition attenuates many of the vascular changes observed in experimental diabetes and may have important clinical implications as a vasoprotective agent in human diabetes.
血管疾病现已成为糖尿病患者发病和死亡的主要原因。我们的研究小组探讨了与实验性糖尿病相关的血管变化，并研究了这些变化是否可以通过抑制血管紧张素转换酶（ACE）来改善。将ACE抑制剂培哚普利（PE）给予链脲佐菌素诱导的糖尿病大鼠，持续24周。在处死时，对肠系膜血管进行体内灌注，然后通过定量组织形态计量学评估血管结构。在一组动物中，从肠系膜血管系统中提取RNA，以评估促硬化细胞因子转化生长因子β1（TGFβ1）和基质蛋白IV型胶原的基因表达。糖尿病与平滑肌肥大和细胞外基质（ECM）积聚有关。在中膜和外膜层观察到ECM积聚，特别是胶原沉积。糖尿病24周后，ACE抑制可预防肠系膜血管肥大。此外，PE治疗可防止糖尿病动物血管中TGFβ1的过度表达。同样，糖尿病血管中IV型胶原mRNA水平升高，PE治疗也可防止这种过度表达。总之，ACE抑制可减轻实验性糖尿病中观察到的许多血管变化，作为一种血管保护剂，可能对人类糖尿病具有重要的临床意义。
