Department of Veterinary Pathology, Key Laboratory of Zoonosis of Ministry of Agriculture, College of Veterinary Medicine, China Agricultural University, Beijing, China.
PLoS One. 2011;6(5):e20008. doi: 10.1371/journal.pone.0020008. Epub 2011 May 23.
To explore the effects of long-term weightlessness on the renal tissue, we used the two months tail suspension model to simulate microgravity and investigated the simulated microgravity on the renal morphological damages and related molecular mechanisms. The microscopic examination of tissue structure and ultrastructure was carried out for histopathological changes of renal tissue morphology. The immunohistochemistry, real-time PCR and Western blot were performed to explore the molecular mechanisms associated the observations. Hematoxylin and eosin (HE) staining showed severe pathological kidney lesions including glomerular atrophy, degeneration and necrosis of renal tubular epithelial cells in two months tail-suspended rats. Ultrastructural studies of the renal tubular epithelial cells demonstrated that basal laminas of renal tubules were rough and incrassate with mitochondria swelling and vacuolation. Cell apoptosis in kidney monitored by the expression of Bax/Bcl-2 and caspase-3 accompanied these pathological damages caused by long-term microgravity. Analysis of the HSP70 protein expression illustrated that overexpression of HSP70 might play a crucial role in inducing those pathological damages. Glucose regulated protein 78 (GRP78), one of the endoplasmic reticulum (ER) chaperones, was up-regulated significantly in the kidney of tail suspension rat, which implied that ER-stress was associated with apoptosis. Furthermore, CHOP and caspase-12 pathways were activated in ER-stress induced apoptosis. Resistance training not only reduced kidney cell apoptosis and expression of HSP70 protein, it also can attenuate the kidney impairment imposed by weightlessness. The appropriate optimization might be needed for the long term application for space exploration.
为了探究长期失重对肾脏组织的影响，我们使用了为期两个月的尾部悬吊模型来模拟微重力，并研究了模拟微重力对肾脏形态损伤和相关分子机制的影响。通过组织学结构和超微结构的显微镜检查，对肾脏组织形态的病理变化进行了研究。采用免疫组织化学、实时 PCR 和 Western blot 技术，探讨了与观察结果相关的分子机制。苏木精和伊红（HE）染色显示，在两个月尾部悬吊大鼠中，肾脏出现严重的病理损伤，包括肾小球萎缩、肾小管上皮细胞变性和坏死。对肾小管上皮细胞的超微结构研究表明，肾小管基底膜粗糙增厚，线粒体肿胀、空泡化。Bax/Bcl-2 和 caspase-3 的表达表明，细胞凋亡伴随着这些由长期微重力引起的病理损伤。HSP70 蛋白表达的分析表明，HSP70 的过度表达可能在诱导这些病理损伤中起关键作用。葡萄糖调节蛋白 78（GRP78）是内质网（ER）伴侣蛋白之一，在尾部悬吊大鼠肾脏中显著上调，这表明 ER 应激与细胞凋亡有关。此外，CHOP 和 caspase-12 途径在内质网应激诱导的细胞凋亡中被激活。阻力训练不仅减少了肾脏细胞凋亡和 HSP70 蛋白的表达，还能减轻失重对肾脏的损伤。为了长期应用于太空探索，可能需要进行适当的优化。
