Acatalasemic mice are mildly susceptible to adriamycin nephropathy and exhibit increased albuminuria and glomerulosclerosis.
Acatalasemic mice are mildly susceptible to adriamycin nephropathy and exhibit increased albuminuria and glomerulosclerosis.
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DOI：
10.1186/1471-2369-13-14
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发表时间：
2012-03-25
期刊：
影响因子：
2.3
通讯作者：
Makino H
中科院分区：
文献类型：
--
作者：
Takiue K;Sugiyama H;Inoue T;Morinaga H;Kikumoto Y;Kitagawa M;Kitamura S;Maeshima Y;Wang DH;Masuoka N;Ogino K;Makino H
过氧化氢酶是一种重要的抗氧化酶，调节细胞内过氧化氢和羟自由基的水平。过氧化氢酶缺乏对蛋白尿和进行性肾小球硬化的影响尚未完全阐明。阿霉素（ADR）肾病模型被认为是局灶节段性肾小球硬化的实验模型。在该模型中，功能性过氧化氢酶缺乏被假设为加剧蛋白尿和肾小球硬化的进展。对纯合子无丙氨酸转氨酶突变小鼠（C3 H/AnLCsbCsb）和对照野生型小鼠（C3 H/AnLCsaCsa）静脉注射ADR。在疾病诱导后8周，比较两组之间肾脏的功能和形态学改变，包括蛋白尿、肾功能、足细胞、肾小球和肾小管间质损伤以及过氧化氢酶活性。此外，Toll样受体4（tlr 4）基因的突变，这是以前报道的C3 H/HeJ株的存在下，在这两个组进行了研究。ADR处理的小鼠出现了显著的蛋白尿和肾小球硬化，并且ADR处理的无丙氨酸血症小鼠中这些状况的程度高于野生型小鼠。ADR仅在无凝血酶血症小鼠中诱导进行性肾纤维化、肾萎缩和脂质过氧化物蓄积。此外，在实验期间，过氧化氢酶活性水平在无丙氨酸血症小鼠的肾脏中显著低于野生型小鼠。野生型小鼠注射ADR后，过氧化氢酶活性增加，但在氧化应激下，无血症小鼠没有能力增加其过氧化氢酶活性。C3 H/AnL株tlr 4基因突变阴性。这些数据表明，过氧化氢酶缺乏在ADR肾病模型中肾损伤的进展中起重要作用。
Catalase is an important antioxidant enzyme that regulates the level of intracellular hydrogen peroxide and hydroxyl radicals. The effects of catalase deficiency on albuminuria and progressive glomerulosclerosis have not yet been fully elucidated. The adriamycin (ADR) nephropathy model is considered to be an experimental model of focal segmental glomerulosclerosis. A functional catalase deficiency was hypothesized to exacerbate albuminuria and the progression of glomerulosclerosis in this model. ADR was intravenously administered to both homozygous acatalasemic mutant mice (C3H/AnLCsbCsb) and control wild-type mice (C3H/AnLCsaCsa). The functional and morphological alterations of the kidneys, including albuminuria, renal function, podocytic, glomerular and tubulointerstitial injuries, and the activities of catalase were then compared between the two groups up to 8 weeks after disease induction. Moreover, the presence of a mutation of the toll-like receptor 4 (tlr4) gene, which was previously reported in the C3H/HeJ strain, was investigated in both groups. The ADR-treated mice developed significant albuminuria and glomerulosclerosis, and the degree of these conditions in the ADR-treated acatalasemic mice was higher than that in the wild-type mice. ADR induced progressive renal fibrosis, renal atrophy and lipid peroxide accumulation only in the acatalasemic mice. In addition, the level of catalase activity was significantly lower in the kidneys of the acatalasemic mice than in the wild-type mice during the experimental period. The catalase activity increased after ADR injection in wild-type mice, but the acatalasemic mice did not have the ability to increase their catalase activity under oxidative stress. The C3H/AnL strain was found to be negative for the tlr4 gene mutation. These data indicate that catalase deficiency plays an important role in the progression of renal injury in the ADR nephropathy model.