Anagnostou A, Vercellotti G, Barone J, Fried W
Blood. 1976 Sep;48(3):425-33.
Current concepts of the pathogenesis of anemia in uremic animals are derived mainly from the results of studies performed either in vitro or in bilaterally nephrectomized animals. These data may not be applicable to the situation which exists in more chronically uremic animals. In 1932, Chanutin and Ferris showed that removal of five-sixths of the renal mass caused rats to become uremic and to remain so for a prolonged period of time. Rats made uremic in this manner were utilized as models for studying the pathogenesis of the anemia of uremia. Removeal of five-sixths of the renal mass of rats caused their BUNs to rise to over 100 mg/100 ml and to remain at this level for over 3 wk. The hematocrits of these uremic rats fell from 42% to approximately 30% in 3 wk. Erythropoietin (Ep) production immediately fell to a barely detectable level postoperatively and did not increase significantly in 3 wk, although the renal remnant hypertrophied. Extrarenal Ep production also remained at a low level and did not increase during the 3-wk observation period. The response of plethoric uremic rats to 2 units of Ep was as great (in some experiments greater) as that of sham-operated ones. A surprising finding was that plethoric uremic rats, injected with saline rather than with Ep, incorporated more 59Fe into their red blood cells than did sham-operated ones. This finding suggested that in uremic rats erythropoiesis was less markedly suppressed by plethora than it was in non-uremic rats.
目前关于尿毒症动物贫血发病机制的概念主要源于体外研究或双侧肾切除动物实验的结果。这些数据可能不适用于慢性尿毒症动物的实际情况。1932年,查努廷和费里斯发现,切除六分之五的肾脏组织会使大鼠患上尿毒症,并在较长时间内维持这种状态。以这种方式造成尿毒症的大鼠被用作研究尿毒症贫血发病机制的模型。切除大鼠六分之五的肾脏组织会使其血尿素氮(BUN)升至100mg/100ml以上,并在3周多的时间里维持在这一水平。这些尿毒症大鼠的血细胞比容在3周内从42%降至约30%。促红细胞生成素(Ep)的产生在术后立即降至几乎检测不到的水平,尽管残余肾脏出现肥大,但在3周内并未显著增加。肾外Ep的产生也维持在较低水平,在3周的观察期内没有增加。充血性尿毒症大鼠对2单位Ep的反应与假手术大鼠一样强烈(在某些实验中更强)。一个令人惊讶的发现是,注射生理盐水而非Ep的充血性尿毒症大鼠,其红细胞摄入的59Fe比假手术大鼠更多。这一发现表明,在尿毒症大鼠中,红细胞生成受多血症的抑制程度不如非尿毒症大鼠明显。