Trojacanec J, Zafirov D, Labacevski N, Jakjovski K, Zdravkovski P, Trojacanec P, Petrusevska G
Department of Preclinical and Clinical Pharmacology with Toxicology, Medical Faculty, Skopje, R. Macedonia.
Pril (Makedon Akad Nauk Umet Odd Med Nauki). 2013;34(1):99-108.
Diabetic nephropathy (DN) is one of the most common causes of terminal stadium damage to the kidneys. The angiotensin-converting enzyme (ACE) represents a significant risk factor for the progression of DN. ACE inhibitors are medications of particular interest knowing the role of angiotensin II in the development of DN. This study aimed to examine the effects of ACE inhibitor treatment perindopril (PER), administered to rats with streptozotocin (STZ) induced DN, that developed albuminuria, renal hypertrophy and mild glomerulussclerosis. DN was induced by a STZ (60 mg/kg ip) single injection to normotensive Wistar rats. The administration of STZ caused diabetes mellitus (DM) with symptoms and signs of DN including poor general condition, body-weight loss, kidney weight increase as well as increased values of BUN and serum creatinine, accompanied by increased diuresis as well as distinct albuminuria. The majority of these symptoms were manifested 4 weeks after, and even more distinctly 8 and 12 weeks after administering STZ. The perindopril treatment (6 mg/kg BW), starting 4 weeks after administering STZ, resulted in a significant improvement of all symptoms and signs of DN, significantly lowering the values of BUN and serum creatinine, albuminuria and diuresis. The histopathological examination of the renal samples at 8 and 12 weeks after the beginning of the study have shown that perindopril significantly lowers the progression of glomerulopathy, and significantly improves the glomerulosclerotic index, as well as the progression of renal histological abnormalities induced with STZ. Thus perindopril treatment ameliorates STZ-induced nephropathic changes in DM rats.
糖尿病肾病（DN）是导致终末期肾脏损害的最常见原因之一。血管紧张素转换酶（ACE）是DN进展的一个重要危险因素。鉴于血管紧张素II在DN发生发展中的作用，ACE抑制剂是特别值得关注的药物。本研究旨在探讨培哚普利（PER）这种ACE抑制剂对链脲佐菌素（STZ）诱导的发生蛋白尿、肾肥大和轻度肾小球硬化的DN大鼠的治疗效果。通过向血压正常的Wistar大鼠单次腹腔注射STZ（60mg/kg）诱导DN。STZ的给药导致糖尿病（DM），伴有DN的症状和体征，包括一般状况不佳、体重减轻、肾脏重量增加以及血尿素氮（BUN）和血清肌酐值升高，同时伴有多尿以及明显的蛋白尿。这些症状大多在给药STZ后4周出现，在8周和12周时更为明显。从给药STZ后4周开始的培哚普利治疗（6mg/kg体重）使DN的所有症状和体征得到显著改善，显著降低了BUN、血清肌酐、蛋白尿和尿量的值。在研究开始后8周和12周对肾脏样本进行的组织病理学检查表明，培哚普利显著降低了肾小球病变的进展，并显著改善了肾小球硬化指数以及STZ诱导的肾脏组织学异常的进展。因此，培哚普利治疗可改善STZ诱导的糖尿病大鼠的肾病性变化。
