Abstract
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.
Highlights
The necessity and advantages of human in the exploration of space have been highlighted by many successful space missions over the past 50 years [1]
No significant difference of the renal index was detected between Tail suspension (TS) group and TS&resistance training (RT) group
A number of studies have demonstrated that renal function is influenced by the environment of weightlessness [31,32,33,34]
Summary
The necessity and advantages of human in the exploration of space have been highlighted by many successful space missions over the past 50 years [1]. As human space travel is more feasible in the twenty-first century, the health and safety of space explorers become the most concerned question. Rattail suspension model was used by National Aeronautics and Space Administration (NASA) to simulate weightlessness on the Earth under laboratory conditions. It was firstly introduced and used by Morey-Holton [2] and later improved by Morey-Holton and Globus [3]. The tail suspension model is considered to be a model to study the effect of body fluid shift which occurred in weightlessness condition [8]
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