Diabetes and hypercholesterolemia experimental study on inhibition of liver fibrosis by angiotensin converting enzymes

Abstract

Purpose: The aim of this study was to evaluate the effect of angiotensin-converting enzyme (ACE) inhibitor on the liver histopathological changes in hypercholesterolemic and diabetic rabbits. Methods: New Zealand rabbits were treated by a single dose of alloxan (100mg iv) and were fed a chow with 0.5% cholesterol for 12weeks. The animals were divided into four groups according to the level of blood glucose: ≥250 mg/dL for groups I (n =10) and II (n=8) or <250mg/dL for groups III (n=12) and IV (n=12) and the groups II and IV were treated with an ACE inhibitor, quinapril (30mg/d) added to the diet. Total serum cholesterol and glucose levels and ACE activity were determined. Histological analysis was performed on liver samples stained with hematoxylin and eosin and picrosirius red. Liver fibrosis was analyzed by Metavir classification and was quantified by Image Tool software in picrosirius polarized images. Results: The four groups were hypercholesterolemic, without significant statistical differences in cholesterol levels among them. ACE activity was lower in the plasma of animals treated with ACE inhibitor (groups II and IV, p<0,01). We observed lower collagen area determined histomorphometrically in the both groups treated with ACE inhibitors, although only in the group with blood glucose control, there have been statistically significant. (p<0.05; group IV

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血管紧张素转换酶抑制糖尿病和高胆固醇血症肝纤维化的实验研究

目的:探讨血管紧张素转换酶(ACE)抑制剂对高胆固醇血症和糖尿病家兔肝脏组织病理学改变的影响。方法:用单剂量四氧嘧啶(100mg iv)治疗新西兰兔，以含0.5%胆固醇的饲料喂养12周。根据血糖水平分为4组:ⅰ组(n= 10)和ⅱ组(n=8)≥250mg/dL，ⅲ组(n=12)和ⅳ组(n=12) <250mg/dL，ⅱ组和ⅳ组在日粮中添加ACE抑制剂喹诺普利(30mg/d)。测定血清总胆固醇、葡萄糖水平及ACE活性。对苏木精、伊红、小天狼星红染色的肝脏标本进行组织学分析。用Metavir分类分析肝纤维化，并用Image Tool软件对微天狼星偏振图像进行量化。结果:四组患者均为高胆固醇血症，各组胆固醇水平差异无统计学意义。ACE抑制剂组血浆ACE活性降低(II组和IV组，p< 0.01)。我们观察到，在ACE抑制剂治疗的两组中，组织形态学测定的胶原面积都较低，尽管只有血糖控制组有统计学意义。(p < 0.05;第四组< III)。结论:我们的研究结果表明，在高胆固醇血症和糖尿病家兔中使用ACE抑制剂对肝脏有保护作用。这项研究强调了肾素-血管紧张素系统在保护受高水平脂质和葡萄糖影响的器官中的重要性。内皮素1被认为是该细胞系最强大的收缩剂，在刺激这些细胞后观察到。抑制不同组织中胶原类型和扩张间质。一些研究显示，卡托普利治疗大鼠胆总管结扎后肝脏中TGF-β 1和前胶原I信使RNA水平降低，支持Ang II在肝星状细胞中的作用假说。24日,30

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