Glasser R J, Velosa J A, Michael A F
Lab Invest. 1977 May;36(5):519-26.
An experimental model of focal sclerosis (FS) following chronic administration of aminonucleoside (AMNS) is described in rats with pathologic features similar to those observed in human steroid-resistant idiopathic nephrotic syndrome. Six groups of rats were given intraperitoneal injections of either 0.9% normal saline or aminonucleoside (13 mg. per 100 gm. of body weight); four groups underwent a right nephrectomy on day 22; a second series of injections of saline or aminonucleoside were then administered to all six groups: group I (five animals), saline-saline; group II (10 animals), AMNS-AMNS; group III (10 animals), AMNS-nephrectomy-AMNS; group IV (five animals), AMNS-nephrectomy-saline; group V (five animals), saline-nephrectomy-AMNS; group VI (five animals), saline-nephrectomy-saline. A relationship between the percentage of glomeruli with focal sclerosis and the total amount of protein excreted during the course of the experiment was observed (r=0.80). An apparent threshold level of protein excretion essential for the development of FS was also noted in that all rats excreting greater than 2.2 integral units developed FS whereas those excreting less than this amount did not. The highest incidence of FS was seen in rats that had received AMNS after unilateral nephrectomy: 62% of glomeruli with FS in group III and 26% in group V; whereas no FS was seen in groups I and VI or in rats evaluated 7 to 23 days after a single injection of AMNS. These studies indicate a quantitative relationship between the breakdown in the permeability barrier to protein and the ultimate development of FS. The prior demonstration of epithelial cell alteration in acute AMNS disease and the morphologic changes presented in this and the subsequent paper (Velosa JA, Glasser RJ, Nevins TE, Michael AF: Lab Invest 36:527, 1977) support the concept that irreversible epithelial cell injury may be the primary event in the development of FS.
本文描述了一种在大鼠中通过长期给予氨基核苷（AMNS）建立的局灶性节段性肾小球硬化（FS）实验模型，其病理特征与人类激素抵抗性特发性肾病综合征中观察到的相似。将六组大鼠分别腹腔注射0.9%生理盐水或氨基核苷（每100克体重13毫克）；四组在第22天进行右肾切除术；然后对所有六组大鼠再次注射生理盐水或氨基核苷：第一组（五只动物），生理盐水-生理盐水；第二组（十只动物），AMNS-AMNS；第三组（十只动物），AMNS-肾切除-AMNS；第四组（五只动物），AMNS-肾切除-生理盐水；第五组（五只动物），生理盐水-肾切除-AMNS；第六组（五只动物），生理盐水-肾切除-生理盐水。观察到局灶性节段性肾小球硬化的肾小球百分比与实验过程中蛋白质排泄总量之间存在相关性（r = 0.80）。还注意到FS发生所必需的蛋白质排泄明显阈值水平，即所有排泄量大于2.2积分单位的大鼠发生了FS，而排泄量小于此值的大鼠则未发生。FS发生率最高的是单侧肾切除后接受AMNS的大鼠：第三组中62%的肾小球有FS，第五组中为26%；而第一组和第六组或单次注射AMNS后7至23天评估的大鼠中未观察到FS。这些研究表明蛋白质通透性屏障破坏与FS最终发展之间存在定量关系。先前在急性AMNS疾病中上皮细胞改变的证明以及本文和后续论文（Velosa JA、Glasser RJ、Nevins TE、Michael AF：实验室研究36:527，1977）中呈现的形态学变化支持了不可逆上皮细胞损伤可能是FS发生的主要事件这一概念。
