Seiken G, Grillo F G, Schaudies R P, Johnson J P
Department of Nephrology, Walter Reed Army Institute of Research, Washington, D.C.
Kidney Int. 1994 Jun;45(6):1622-7. doi: 10.1038/ki.1994.213.
Administration of either thyroid hormone or epidermal growth factor (EGF) ameliorates injury in a variety of experimental acute renal failure (ARF) models. Since thyroid hormone augments EGF release and EGF receptor expression, a hypothesis suggesting that the mechanism of thyroid action is via EGF appears attractive. The present study is an attempt to evaluate the role of EGF in thyroid mediated protection from ARF induced in rats by dichromate. Renal parenchymal levels of acid extractable endogenous EGF were measured by RIA in dichromate exposed, otherwise untreated animals and in those receiving dichromate followed by thyroid. In the untreated case serum creatinine peaked at 2.5 mg % on the third day following dichromate exposure. Endogenous levels of EGF closely paralleled serum creatinine with a six-fold increase observed at peak injury. The source of EGF increase appeared to be a membrane bound precursor as soluble levels of EGF rose in injured kidneys at the expense of Triton-X-100 extractable, immunoreactive material that upon treatment with trypsin yielded additional EGF. T3 administered one hour following dichromate resulted in significant functional protection (peak injury serum creatinines 2.63 +/- 0.76 control vs. 0.98 +/- 0.14 with T3) as well as an approximate doubling in renal EGF levels at 24, 48 and 72 hours (4.7 +/- 0.3 vs. 9.7 +/- 0.8 at 24 hr, 33.5 +/- 6.5 vs. 63.2 +/- 20.0 at 48 hr, and 23.1 +/- 10.0 vs. 44.1 +/- 8.7 ng/g wet weight at 72 hr). There was no beneficial effect of exogenous EGF on renal function either when given in conjunction with T3 or when used alone.(ABSTRACT TRUNCATED AT 250 WORDS)
给予甲状腺激素或表皮生长因子（EGF）均可改善多种实验性急性肾衰竭（ARF）模型中的损伤。由于甲状腺激素可增加EGF的释放及EGF受体的表达，因此认为甲状腺作用机制是通过EGF的这一假说颇具吸引力。本研究旨在评估EGF在甲状腺介导的对重铬酸盐诱导的大鼠ARF的保护作用中的角色。通过放射免疫分析法（RIA）测定重铬酸盐暴露但未接受其他处理的动物以及接受重铬酸盐后再给予甲状腺激素的动物肾实质中酸可提取的内源性EGF水平。在未处理的情况下，重铬酸盐暴露后第三天血清肌酐峰值达到2.5mg%。内源性EGF水平与血清肌酐密切平行，在损伤峰值时观察到增加了6倍。EGF增加的来源似乎是一种膜结合前体，因为受损肾脏中EGF的可溶性水平升高，而牺牲了经Triton-X-100可提取的免疫反应性物质，该物质经胰蛋白酶处理后可产生额外的EGF。重铬酸盐暴露1小时后给予T3可产生显著的功能保护作用（损伤峰值时血清肌酐：对照组为2.63±0.76，T3组为0.98±0.14），并且在24、48和72小时时肾EGF水平大约翻倍（24小时时分别为4.7±0.3和9.7±0.8，48小时时分别为33.5±6.5和63.2±20.0，72小时时分别为23.1±10.0和44.1±8.7ng/g湿重）。外源性EGF无论是与T3联合给予还是单独使用，对肾功能均无有益作用。（摘要截短至250字）
