Hall R L, Wilke W L, Fettman M J
Toxicol Appl Pharmacol. 1986 Jan;82(1):164-74. doi: 10.1016/0041-008x(86)90448-5.
The progression of adriamycin-induced nephrotic syndrome in rats was studied over a 3-month period. The effect of an angiotensin-converting enzyme inhibitor, captopril, on this model of renal disease, was also studied. Two weeks following a single iv injection of adriamycin, rats were divided into two treatment groups: one received a daily po dose of captopril and the other received a placebo. Measurements of renal function were performed at 4, 8, and 11 weeks following the initiation of therapy. Necropsies and light microscopic evaluation of the kidneys were performed at the end of the treatment period. Functional and morphologic alterations in both groups of rats were compared to each other and to normal age/weight-matched control rats studied over the same time period. At 13 weeks following the administration of adriamycin, both treatment groups had significant renal dysfunction when compared to normal controls. In addition to severe proteinuria, rats receiving adriamycin exhibited polyuria, polydipsia, increased plasma urea nitrogen and plasma creatinine, and decreased endogenous creatinine clearance. They had severe generalized kidney lesions characterized by tubular dilation and atrophy, cast formation, interstitial fibrosis and lymphocytic infiltration, and focal, global glomerulosclerosis. The histopathologic ranking of the kidneys was correlated with some antemortem laboratory parameters but not with the degree of proteinuria. Captopril had no ameliorating effects on the progression of renal disease. Certain findings indicate that captopril may actually have promoted the deterioration of renal function. We conclude that adriamycin-induced nephrotic syndrome in the rat is a progressive disease resulting in generalized renal dysfunction, and that captopril, at the dose given in this experiment, is unable to slow the progression of the disease.
在3个月的时间里研究了阿霉素诱导的大鼠肾病综合征的进展情况。还研究了血管紧张素转换酶抑制剂卡托普利对这种肾脏疾病模型的影响。单次静脉注射阿霉素两周后，将大鼠分为两个治疗组：一组每日口服卡托普利，另一组服用安慰剂。在开始治疗后的第4、8和11周进行肾功能测量。在治疗期结束时进行肾脏尸检和光学显微镜评估。将两组大鼠的功能和形态学改变相互比较，并与在同一时期研究的正常年龄/体重匹配的对照大鼠进行比较。在给予阿霉素13周后，与正常对照组相比，两个治疗组均出现明显的肾功能障碍。除严重蛋白尿外，接受阿霉素的大鼠还表现出多尿、多饮、血浆尿素氮和血浆肌酐升高，以及内生肌酐清除率降低。它们有严重的全身性肾脏病变，其特征为肾小管扩张和萎缩、管型形成、间质纤维化和淋巴细胞浸润，以及局灶性、全球性肾小球硬化。肾脏的组织病理学分级与一些生前实验室参数相关，但与蛋白尿程度无关。卡托普利对肾脏疾病的进展没有改善作用。某些发现表明卡托普利实际上可能促进了肾功能的恶化。我们得出结论，阿霉素诱导的大鼠肾病综合征是一种进行性疾病，会导致全身性肾功能障碍，并且在本实验中给予的剂量下，卡托普利无法减缓疾病的进展。
