Effect of diet, age and sex on the renal response to immune injury in the rat.
Effect of diet, age and sex on the renal response to immune injury in the rat.
复制标题
饮食、年龄和性别对大鼠肾脏对免疫损伤反应的影响。
DOI：
10.1038/ki.1988.34
复制
发表时间：
1988
影响因子：
19.6
通讯作者：
Ichikawa,I
中科院分区：
文献类型：
--
作者：
Yared,A;Miyazawa,H;Purkerson,ML;Klahr,S;Salant,DJ;Ichikawa,I
饮食、年龄和性别对大鼠免疫损伤后肾小球反应的影响。我们研究了三个因素的影响，即膳食蛋白质摄入量，年龄和性别，对肾小球的敏感性结合的抗肾小球基底膜抗体（抗GBM）在早期（异源）阶段的抗GBM肾炎，并随之降低肾小球滤过率（GFR）测定菊粉清除率（CIn）。在喂食40%高（HP）或6%低（LP）蛋白质饮食的108周龄雌性Munich-Wistar大鼠中检查饮食的影响，并在6周龄或10月龄的雄性和雌性大鼠中检查性别和年龄的影响。静脉注射放射性标记的致肾炎抗GBM（3 - 20 µg/g体重）后，评估肾小球功能，然后定量分离肾小球中的抗GBM结合（根据GBM表面积校正的值）。在给定的血浆抗体水平下，HP大鼠的抗GBM结合程度略高于LP喂养大鼠，但显著高于LP喂养大鼠; HP大鼠的GFR降低显著高于LP喂养动物。抗GBM结合的量在成年动物中显著大于幼年动物;然而，随之而来的GFR降低在幼年动物中比成年动物更明显。在抗GBM结合或GFR降低方面，性别依赖性不可辨别。在所有上述实验组中，抗GBM结合的程度与血浆抗GBM水平密切相关，但与通过PAH清除率测量的有效肾血浆流速无关。通过部分主动脉收缩和saralasin给药，对单独的大鼠组进行单个肾单位GFR、肾小球毛细血管液压和肾小球血浆流速的实验操作。使用示踪量的非致肾炎性抗GBM的这组实验揭示了肾小球抗GBM结合不依赖于任何上述参数。研究表明，饮食蛋白质摄入量和年龄，而不是性别，是决定肾小球对急性免疫损伤敏感性的因素。由于抗GBM的结合是由肾小球本身的亲和力性质决定的，而不是由流行的血液动力学模式决定的，所观察到的对功能损害的易感性对年龄和蛋白质摄入的依赖性似乎也反映了肾小球的性质，其受年龄和饮食蛋白质摄入程度的影响。
Effect of diet, age and sex on the glomerular response to immune injury in the rat. We investigated the effect of three factors, namely dietary protein intake, age and sex, on the susceptibility of the renal glomerulus to the binding of antiglomerular basement membrane antibody (anti-GBM) in the early (heterologous) phase of anti-GBM nephritis, and the consequent reduction in glomerular filtration rate (GFR) as measured by inulin clearance (CIn). The effect of diet was examined in ≈ 8 week-old female Munich-Wistar rats fed a 40% high (HP) or a 6% low (LP) protein diet, and that of sex and age in male and female rats, 6 week or 10 month old. Following an intravenous dose (3 to 20 µg/g body wt) of radiolabeled nephritogenic anti-GBM, assessment of glomerular function was followed by quantitation of anti-GBM binding (values corrected for GBM surface area) in isolated glomeruli. At a given plasma level of antibody, the degree of binding of anti-GBM was slightly but significantly higher in HP than LP-fed rats; the decrease in GFR was significantly more pronounced in HP than LP-fed animals. The amount of anti-GBM binding was significantly greater in adult than young animals; however, the consequent decrease in GFR was more pronounced in the young than adult animals. Sex dependency was not discernible in anti-GBM binding or reduction in GFR. In all of the above experimental groups, the degree of anti-GBM binding was closely correlated with the plasma level of anti-GBM, but not with effective renal plasma flow rate, measured by PAH clearance. Separate groups of rats were subjected to experimental manipulation of single nephron GFR, glomerular capillary hydraulic pressure and glomerular plasma flow rate, by partial aortic constriction and saralasin administration. This set of experiments, using a tracer amount of non-nephritogenic anti-GBM, revealed that glomerular anti-GBM binding is independent of any of the above parameters. The studies indicate that dietary protein intake and age, but not sex, are among the factors determining the susceptibility of the glomerulus to acute immune injury. Since the binding of anti-GBM is determined by the affinity property of the glomerulus per se, and not by the prevailing hemodynamic pattern, the observed dependence of susceptibility to functional impairment on age and protein intake appears to also reflect a property of the glomerulus, which is influenced by age and the degree of dietary protein intake.