Abstract: Objective To investigate the molecular mechanisms of diaphragm injury in rats with liver cirrhosis. Methods Thirty
adult male Sprague-Dawley rats were randomized into control group (n=10) and carbon tetrachloride-induced liver cirrhosis
group (LC group, n=20). In the 9th week, the rat body weight and diaphragm to body weight ratio were measured, and the
parameters of diaphragm contractility including peak twitch tension (Pt), maximum tetanic tension (Po), time to peak
contraction (CT), half relaxation time (1/2RT), and force-frequency curve were assessed using a Medlab-U/4C biological signal
collecting system. The activities of superoxide dismutase (SOD), succinic dehydrogenase (SDH) and myeloperoxidase (MPO)
and malondiadehyde (MDA) content in the diaphragm were detected. The mRNA expression levels of sarcoplasmic reticulum
calcium ATPase (SERCA) and cytoskeletal proteins (titin and nebulin) in the diaphragm were detected by RT-PCR, and the
diaphragm ultrastructure was examined with electron microscopy. Results Compared with those in the control group, body
weight, diaphragm to body weight ratio, Pt, Po, and tetanic force under the stimulus frequency of 10, 20, 40, 60, 100 Hz were all
significantly decreased (P<0.01), while CT and 1/2RT were significantly prolonged in LC group (P<0.01). SOD and SDH
activities were significantly lowered (P<0.01) while the contents of MDA and MPO activity were significantly increased in LC
group (P<0.01) with significantly decreased SERCA, titin and nebulin mRNA expressions in the diaphragm (P<0.01). Electron
microscopy of the diaphragm in LC group revealed myofibrillar degeneration, absence of the Z line, and mitochondria
swelling and edema. Conclusions Liver cirrhosis increases free radicals and aggravates inflammatory response and lipid
peroxidation in the diaphragm, thus leading to mitochondrial damages and decreased expressions of cytoskeletal proteins and
SERCA to cause diaphragmatic dysfunction.