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In 1957, Jacobson et al performed bilateral nephrectomies on rats and showed that these animals no longer responsed to phlebotomy or cobalt administration with increased Ep production. Rats that only had their ureters ligated and that developed similar elevations of the blood urea nitrogen still responded to cobalt or phlebotomy in the usual fashion .Similiar results were found in mice , rabbits , baboons , and dogs .In humans , Ep levels were found to be low in the serum of anemic patients with severe uremia , but after successful renal transplantation increases in blood Ep levels and hematocrit were observed. Furthermore , erythropoietic activity was detected in the perfusates from isolated rabbit kidneys and was produced by renal cell cultures in vitro . Although the evidence to support the renal origin of Ep was substantial , Ep had not been extracted from normal kidneys or from various normal kidney fractions until very recently. To explain this difficulty , three different hypotheses have been proposed . Current evidence indicates that the stimulation of Ep production by hypoxia or ischemia may be mediated via increases in renal prostaglandin and cyclic AMP levels . The administration of cyclic AMP to plethoric mice increased Ep production and led to and increased red cell mass in normal mice . prostaglandin raised the renal cyclic AMP concentration in isolated perfused dog kidneys as well as the amount of Ep in the perfusates ;the administration of prostaglandin to polycythemic mice increased both prostaglandin E and Ep blood levels in dogs . The effect on both these parameters as well as on hypoxia-induced Ep production was blocked by indomethacin, a known inhibitor of prostaglandin synthesis .Since prostaglandins are located mainly in the renal medulla , while Ep has been identified by fluorescent antibodies in the renal cortex , these observations are most consistent with the hypothesis that renal hypoxia or ischemia produces a medullary release of prostaglandin which in turn elevates renal corticla cyclic AMP levels. The newly formed cyclic AMP THEN may activate a protein kinase that leads to increased Ep production , possibly through phosphorylation of a precursor renal erythropoietic factor. Although the kidney is the major site controlling Ep formation , after bilateral nephrectomy the production of hormone and erythropoiesis continues in most species , but at a considerably lower level .Anephric mice and rats retain about 10%of their original capacity to increase Ep production in the presence of hypoxia , while anephric patients who become very anemic have Ep in their plasma .The extrarenal Ep of rats appears to be similar to Ep of renal origin since it stimulates heme synthesis by marrow cells and is neutralized by antiserum to urinary Ep . Several lines of study point to the liver as the primary site of extrarenal Ep production. Ep is produced primarily in the liver during fetal life .Hepatectomy abolishes hypoxia-stimulated hormone production in anephric rats , but not in animals with intact kidneys . In partially hepatectomized rats , the extrarenal Ep response to hypoxia correlates directly with liver regeneration and is most increased during the period of greatest proliferation . Administration of colloidal carbon or zymosan, which induces liver reticuloendothelial cell hyperplasia, enhances Ep production in nephrectomized rats exposed to hypoxia .This effect, which is also blocked by hepatectomy , suggests that the liver reticuloendothelial system may be and important factor in extrarenal Ep production . |
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ringzhu(金币+10): 辛苦~~ 2011-03-17 15:20:37
ringzhu(金币+10): 辛苦~~ 2011-03-17 15:20:37
| In 1957, Jacobson et al performed bilateral nephrectomies on rats and showed that these animals no longer responsed to phlebotomy or cobalt administration with increased Ep production. 1957年，Jacobson等人对小白鼠进行了双肾切除实验，双肾切除后的小白鼠的上皮细胞数量增加，但对放血和钴刺激无任何反应。Rats that only had their ureters ligated and that developed similar elevations of the blood urea nitrogen still responded to cobalt or phlebotomy in the usual fashion .而输尿管结扎并血液尿素氮的含量增加的小白鼠通常对放血和钴刺激仍有反应。Similiar results were found in mice , rabbits , baboons , and dogs .对老鼠，兔子，狒狒和狗进行实验，也发现了相同的结果。In humans , Ep levels were found to be low in the serum of anemic patients with severe uremia , 而人体实验表明严重尿毒症患者血清中上皮细胞数量低，but after successful renal transplantation increases in blood Ep levels and hematocrit were observed. 但经成功的肾脏移植手术后，血液中的上皮细胞数量增加并观察到有血细胞（hematocrit,这个单词查了，还是不清楚）Furthermore , erythropoietic activity was detected in the perfusates from isolated rabbit kidneys and was produced by renal cell cultures in vitro . 另外，我们从切割下的兔子的肾脏中和在试管中培养的肾细胞中检测到了红细胞。Although the evidence to support the renal origin of Ep was substantial , Ep had not been extracted from normal kidneys or from various normal kidney fractions until very recently.虽然目前有足够的证据能证明上皮细胞来源于肾脏，但是也只是最近才在正常的肾脏中或肾脏的不同组织中才提取出上皮细胞To explain this difficulty , three different hypotheses have been proposed .为了解释这个问题，人们提出了三种假设。 |
6楼2011-03-09 15:48:12
wjmsicuan(金币+1, 翻译EPI+1): 很差劲，不过还是慰问下！！ 2011-03-06 19:43:10
 在1957年，Jacobson 等人对大鼠首先进行双侧肾切除，之后放血或用钴处理，发现Ep不增高，然而，如果预先只是将大鼠输尿管结扎，其血液尿素含量增高，之后放血或用钴处理，其Ep，和正常鼠一样，增高。在小鼠，家兔，狒狒和狗身上做相同的实验，获得的结果相似。在人群中，伴有严重尿毒症的白血病患者的血液Ep水平较低，但在肾移植手术成功后，血液Ep水平升高，且血细胞计数也有所增加。此外，对分离的家兔的肾灌流液，即体外培养的肾细胞的红血球生成活性进行检测。虽然支持Ep 来源于肾的证据可靠，但直到现在，人们还没能从正常的肾或不同的肾fractions提取出 Ep 。为了解释这个难题，三个不同的假说被提出。最新证据显示，由组织缺氧和局部缺血诱导的 Ep的产生是通过上调肾脏前列腺素和cAMP水平来介导的。用cAMP处理多血症小鼠可增加Ep的产生，处理正常小鼠可导致红细胞块的增加。前列腺可以上调体外灌流的狗肾脏的cAMP浓度，同时也可以上调灌流液中Ep含量。用前列腺素处理红细胞增多小鼠，可以增加血液前列腺素E含量，也可以增加狗的血Ep含量。对这2个参数的影响和组织缺氧诱导的Ep增多可以被消炎药茚甲新阻断，茚甲新是前列腺素合成的抑制剂。由于前列腺素主要分布于肾髓，而Ep已通过荧光抗体被鉴定存在于肾皮质， 这些观察结果与假设一致，即肾缺氧或缺血诱导肾髓释放前列腺素，而前列腺素反过来又上调肾皮质的cAMP浓度。新生成的cAMP，接下来可能可以激活蛋白激酶增加Ep的产生，很可能是通过磷酸化肾红血球生成因子前体来实现的。 虽然肾是控制Ep生成的主要场所，在大多数物种经历双肾切除手术之后，激素和红血球产生过程仍然继续，只是以相当低的速度。无肾小鼠和无肾大鼠在缺氧条件下仍然保留约10%生产Ep的能力,但无肾的病人，常表现为严重贫血，在血浆中含有Ep。大鼠肾外的Ep和肾来源的Ep很相似，也可以刺激骨髓细胞生成亚铁血红素，可以被抗尿Ep的抗血清中和。一些研究团队认为肝脏是肾外Ep产生的最初部位。在胎儿期 Ep主要在肝脏中产生。在无肾大鼠中，肝脏切除可以阻断低氧诱导激素的产生，但在有完整肾的动物中肝脏切除不可阻断。在部分肝脏切除的大鼠中， 肾外Ep对低氧的反应直接与肝再生相关，且在增殖最旺盛期肾外Ep增加最快。 用胶状碳或酵母聚糖诱导肝网状内皮组织增生，可以促进受低氧胁迫的肾切除大鼠的Ep的产生。这个效应同样可以被肝切除手术阻断，提示肝网状内皮系统 可能是肾外Ep产生的重要因素。 第一次翻译，凑活着看啊 |
2楼2011-03-05 20:56:56
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