The Effect Of Calpain On The Diaphragm Injury And Atrophy Under Mechanical Ventilation In Rats

Objective: Controlled mechanical ventilation (CMV) results in a rapid onset ofdiaphragm dysfunction that is primarily due to elevated diaphragmatic proteolysis. Calpainsactivation may also be involved in muscle wasting caused by CMV and play an important rolein ventilator-induced diaphragm injury and atrophy. The study was to discuss the effect ofcalpain on diaphragmatic injury and atrophy under controlled mechanical ventilation in rats.Methods: A total of24Sprague Dawley rats (8in each group) were randomly dividedinto control group,24hours of CMV and treatment with4mg/kg calpeptin group (CMVC).Variants of diaphragm ultrastructure, light microscopic feature and myosin heavy chainexpression were observed.Results:(1) The signs of misalignment of myofibrils, disruption of Z-band and vacuolarmitochondria were found in CMV. The density of muscle injury in CMV (36.0±15.4)×10-2/μm2is significantly higher compared with that in control group (6.0±7.1)×10-2/μm2andthat in CMVC [(16.0±9.6)×10-2/μm2](P<0.05, respectively).(2) Abnormal viable, internalnuclei and swelling of capillary endothelial cells could be observed in CMV. The mean CSAdiaphragm fiber in CMV (6700±614)μm2is significantly lower compared with that incontrol group (14606±1115)μm2and that in CMVC [(10458±1059)μm2](P<0.05,respectively).(3) In CMV, the densities of MHCslowand MHCfastwere lower compared withthe control group, especially MHCfast(61.1%vs.77.1%). However, the densities of MHCslowand MHCfastwere increased after treatment with calpeptin, and MHCslowelevated moresignificantly.Conclusions: Calpeptin reversed the detrimental effects of CMV-induced diaphragmaticinjury and atrophy，which suggested that calpain play an important role in modulating theventilator-induced diaphragm dysfunction.