Morphology and Molecular Mechanisms of Hepatic Injury in Rats under Simulated Weightlessness and the Protective Effects of Resistance Training

Abstract

This study investigated the effects of long-term simulated weightlessness on liver morphology, enzymes, glycogen, and apoptosis related proteins by using two-month rat-tail suspension model (TS), and liver injury improvement by rat-tail suspension with resistance training model (TS&RT). Microscopically the livers of TS rats showed massive granular degeneration, chronic inflammation, and portal fibrosis. Mitochondrial and endoplasmic reticulum swelling and loss of membrane integrity were observed by transmission electron microscopy (TEM). The similar, but milder, morphological changes were observed in the livers of TS&RT rats. Serum biochemistry analysis revealed that the levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) were significantly higher (p<0.05) in TS rats than in controls. The levels of ALT and AST in TS&RT rats were slightly lower than in RT rats, but they were insignificantly higher than in controls. However, both TS and TS&RT rats had significantly lower levels (p<0.05) of serum glucose and hepatic glycogen than in controls. Immunohistochemistry demonstrated that the expressions of Bax, Bcl-2, and active caspase-3 were higher in TS rats than in TS&RT and control rats. Real-time polymerase chain reaction (real-time PCR) showed that TS rats had higher mRNA levels (P < 0.05) of glucose-regulated protein 78 (GRP78) and caspase-12 transcription than in control rats; whereas mRNA expressions of C/EBP homologous protein (CHOP) and c-Jun N-terminal kinase (JNK) were slightly higher in TS rats. TS&RT rats showed no significant differences of above 4 mRNAs compared with the control group. Our results demonstrated that long-term weightlessness caused hepatic injury, and may trigger hepatic apoptosis. Resistance training slightly improved hepatic damage.

Hepatitis E Virus Induces Hepatocyte Apoptosis via Mitochondrial Pathway in Mongolian Gerbils

“…Bax acts downstream in the mitochondrial apoptotic pathway and it represents a key molecule in this process. As a component of the mitochondrial electron transfer chain, cytochrome c can initiate caspase activation following its release from mitochondria, binding to Apaf-1 ( Du et al, 2015 ). Afterward, Apaf-1-cytochrome c complex forms apoptosome, which recruits procaspase-9 and initiates the formation of the caspase-9 holoenzyme that cleaves and activates downstream caspases, such as caspase-3.…”

“…Afterward, Apaf-1-cytochrome c complex forms apoptosome, which recruits procaspase-9 and initiates the formation of the caspase-9 holoenzyme that cleaves and activates downstream caspases, such as caspase-3. Furthermore, the recruitment of Bax leads to permeabilization of mitochondrial outer membrane ( Wang, 2001 ; Du et al, 2015 ), which is considered one of the key control switches of the apoptotic process ( Ferreira et al, 2008 ). Here, we demonstrated that cytochrome c was released into the cytosol in the inoculated group, and this represents a biomarker indicating the activation of the mitochondrial apoptotic pathway ( Pan et al, 2014 ).…”

“…A total of 15 fields per gerbil (three fields per section, five sections per gerbil, 400× magnification) were randomly selected and analyzed. The positive staining intensity was calculated as the ratio of the stained area to the total field assessed ( Du et al, 2015 ).…”

Estrogen inhibits the overgrowth of Escherichia�coli in the rat intestine under simulated microgravity

“…The animals were treated as previously described ( 13 ). Briefly, Male Wistar rats (Eight-week-old, approximately 250 g) were purchased from the Experimental Animal Center, Academy of Military Medical Sciencs.…”

The Effects of Two Anesthetics, Propofol and Sevoflurane, on Liver Ischemia/Reperfusion Injury

“…As in this study, once the expression of pro-apoptotic proteins such as Bax and Bak or of antiapoptotic proteins such as Bcl-2 and Bcl-xl was altered, cytochrome c would be released from the intermembrane space. As a component of the mitochondrial electron transfer chain, cytochrome c could initiate caspase activation, including caspase 9 and caspase 3, ultimately induced apoptosis in hepatic injury [43]. A number of studies reported that p38 MAPK and AKT were activated by ROS and cytokines [44][45][46].…”