Compensatory thrombopoietin production from the liver and bone marrow stimulates thrombopoiesis of living rat megakaryocytes in chronic renal failure.

Nephron Extra Pub Date : 2011-01-01 Epub Date: 2011-10-22 DOI:10.1159/000333018

Itsuro Kazama, Yasuhiro Endo, Hiroaki Toyama, Yutaka Ejima, Shin Kurosawa, Yoshimichi Murata, Mitsunobu Matsubara, Yoshio Maruyama

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Abstract

Background/aims: Decreased thrombopoiesis has been ascribed a role in the pathogenesis of uremic bleeding in chronic renal failure (CRF). However, serum thrombopoietin (TPO) levels are usually elevated in CRF patients, suggesting increased thrombopoiesis. The aim of this study was to determine the thrombopoietic activity in CRF.

Methods: Male Sprague-Dawley rats that underwent 5/6 nephrectomy were used as the model of CRF. Age-matched sham-operated rats were used as controls. Single megakaryocytes were isolated from the rat bone marrow, and their size distribution was examined. Megakaryocyte membrane invaginations were monitored by confocal imaging of di-8-ANEPPS staining, and patch clamp whole-cell recordings of membrane capacitance. TPO gene expression was assessed in various tissues.

Results: Circulating platelet counts and the number of large megakaryocytes were increased in the bone marrow of CRF rats. Massive di-8-ANEPPS staining and increased membrane capacitance in large megakaryocytes demonstrated increased membrane invaginations. Unaffected Kv1.3-channel currents per cell surface area demonstrated unaltered channel densities. TPO transcription was decreased in the renal cortex but increased in the liver and bone marrow of CRF rats.

Conclusion: Increased thrombopoiesis in CRF was thought to be a reactive mechanism to platelet dysfunction. Increased TPO production from the liver and bone marrow compensated for decreased production from damaged kidneys.

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肝脏和骨髓产生的补偿性血小板生成素可刺激慢性肾衰竭大鼠巨核细胞的血栓形成。

背景/目的：慢性肾功能衰竭（CRF）尿毒症出血的发病机制之一是血栓形成减少。然而，慢性肾功能衰竭患者的血清血小板生成素（TPO）水平通常升高，表明血栓生成增加。本研究旨在确定慢性肾功能衰竭患者的血栓生成活性：方法：以接受 5/6 肾切除术的雄性 Sprague-Dawley 大鼠为 CRF 模型。以年龄匹配的假手术大鼠为对照组。从大鼠骨髓中分离出单个巨核细胞，并检测其大小分布。通过双8-ANEPPS染色共焦成像和膜电容膜片钳全细胞记录监测巨核细胞膜内陷。对不同组织中的 TPO 基因表达进行了评估：结果：CRF 大鼠骨髓中的循环血小板计数和大巨核细胞数量增加。大巨核细胞的di-8-ANEPPS染色和膜电容增加表明膜内陷增加。每个细胞表面积的 Kv1.3 通道电流未受影响，这表明通道密度没有改变。TPO转录在CRF大鼠的肾皮质中减少，但在肝脏和骨髓中增加：结论：CRF 大鼠血栓生成增加被认为是血小板功能障碍的一种反应机制。肝脏和骨髓产生的 TPO 增加可补偿受损肾脏产生的 TPO 减少。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Nephron Extra

自引率

0.00%

发文量

审稿时长

12 weeks

期刊介绍： An open-access subjournal to Nephron. ''Nephron EXTRA'' publishes additional high-quality articles that cannot be published in the main journal ''Nephron'' due to space limitations.