title: Study of histopathological and molecular changes of rat kidney under simulated weightlessness and resistance training protective effect.
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.
authors.affiliation: Department of Veterinary Pathology, Key Laboratory of Zoonosis of Ministry of Agriculture, College of Veterinary Medicine, China Agricultural University, Beijing, China.
authors.forename: Ye
authors.initials: Y
authors.lastname: Ding
authors.forename: Jun
authors.initials: J
authors.lastname: Zou
authors.forename: Zhili
authors.initials: Z
authors.lastname: Li
authors.forename: Jijing
authors.initials: J
authors.lastname: Tian
authors.forename: Saed
authors.initials: S
authors.lastname: Abdelalim
authors.forename: Fang
authors.initials: F
authors.lastname: Du
authors.forename: Ruiping
authors.initials: R
authors.lastname: She
authors.forename: Desheng
authors.initials: D
authors.lastname: Wang
authors.forename: Cheng
authors.initials: C
authors.lastname: Tan
authors.forename: Huijuan
authors.initials: H
authors.lastname: Wang
authors.forename: Wenjuan
authors.initials: W
authors.lastname: Chen
authors.forename: Dongqiang
authors.initials: D
authors.lastname: Lv
authors.forename: Lingling
authors.initials: L
authors.lastname: Chang
mesh_terms: D000818:Animals; D017209:Apoptosis; D015153:Blotting, Western; D000091342:Endoplasmic Reticulum Chaperone BiP; D006360:Heat-Shock Proteins / Q000378:metabolism; D007150:Immunohistochemistry; D007668:Kidney / Q000033:anatomy & histology* / Q000378:metabolism / Q000648:ultrastructure; D046529:Microscopy, Electron, Transmission; D010805:Physical Conditioning, Animal; D016133:Polymerase Chain Reaction; D051381:Rats; D015854:Up-Regulation; D014893:Weightlessness
chemical_list: D000091342:Endoplasmic Reticulum Chaperone BiP; D006360:Heat-Shock Proteins