title: [Changes of sarcoplasmic reticulum calcium ATPase, titin, and nebulin expressions in the diaphragm of rats with liver cirrhosis].
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.
authors.affiliation: Department of Pharmacology, Bengbu Medical College, Bengbu 233030, China. E-mail: geminbbmc@163.com.
authors.forename: Min
authors.initials: M
authors.lastname: Ge
authors.forename: Li
authors.initials: L
authors.lastname: Ma
authors.forename: Yingyan
authors.initials: Y
authors.lastname: Fang
authors.forename: Weiping
authors.initials: W
authors.lastname: Zhang
authors.forename: Sudong
authors.initials: S
authors.lastname: Guan
mesh_terms: D000818:Animals; D001835:Body Weight; D002251:Carbon Tetrachloride; D064211:Connectin / Q000378:metabolism*; D003964:Diaphragm / Q000378:metabolism*; D015227:Lipid Peroxidation; D008099:Liver / Q000201:enzymology / Q000473:pathology; D008103:Liver Cirrhosis / Q000378:metabolism*; D008297:Male; D009119:Muscle Contraction; D009124:Muscle Proteins / Q000378:metabolism*; D010084:Oxidation-Reduction; D051381:Rats; D017207:Rats, Sprague-Dawley; D053498:Sarcoplasmic Reticulum Calcium-Transporting ATPases / Q000378:metabolism*
chemical_list: D064211:Connectin; D009124:Muscle Proteins; C577295:Ttn protein, rat; C035620:nebulin; D002251:Carbon Tetrachloride; D053498:Sarcoplasmic Reticulum Calcium-Transporting ATPases