Effect Of MG53 Gene Knockout On The Expression Of Endoplasmic Reticulum Stress Protein GRP78 And Caspase12 In Triceps Muscles After A One-time Downhill Run In Mice

Objective: Endoplasmic reticulum stress response as an endogenous protective mechanism has important pathophysiological significance for the body's exercise skeletal muscle injury.Sustained or high-intensity endoplasmic reticulum stress response activates the endoplasmic reticulum stress pathway.Apoptotic signaling pathway leads to apoptosis.In recent years,studies have found that a membrane damage repair protein MG53 that is specifically expressed in skeletal muscle/myocardium plays a central role in membrane damage repair.Exercise skeletal muscle injury process leads to damage to the membrane and endoplasmic reticulum stress,so whether MG53 has an effect on endoplasmic reticulum stress is unknown.Therefore,this article explores the effects of MG53 knockdown on the skeletal muscle endoplasmic reticulum stress response after a one-time downhill run-induced skeletal muscle motor injury,repairs the skeletal muscle injury and reduces the exercise-induced endoplasmic reticulum.Stress response provides a new perspective.Subjects and methods: 60 healthy MG53 knockout(KO)mice and 60 wild-type(WT)mice,aged 11-12 weeks,were randomly divided into KO WT quiet control group and KO WT exercise group,the KO WT exercise group is divided into immediate group after exercise(E0),2h after exercise(E2),24 h after exercise(E24),48 h after exercise(E48),and 72 h after exercise(E72),10 per group.Movement model: the first 20 minutes of exercise,the movement speed is 16m/min,the gradient is gradually reduced from 0%(grade)to-14%(grade);after 20 minutes of exercise,the movement speed is adjusted to 22m/min,and the slope is maintained at-14%(grade)The total length of exercise is 150 minutes.After the exercise,each group of mice was sacrificed at 0h,2h,24 h,48h,72 h.The mice were harvested with eyeballs to detect changes in serum CK and LDH activity;the left and right triceps muscles were taken,the left side was used for observation of muscle tissue under electron microscope,and the right side was detected by Western blot for endoplasmic reticulum stress-related protein expression.And SOD,MDA determination.Image acquisition and data processing were performed using Tanon-5200 chemiluminescence imager and Tanon Gis analysis software,and statistical analysis was performed using SPSS20.0 software.Results: Immediately after a one-time downhill run,the activities of serum CK and LDH in KO and WT mice increased,followed by a downward trend.The serum CK activity of KO-E0 and KO-E24 phase groups was significantly higher than that of WT-.EO,WT-E24 phase group(P<0.01),KO-E0,KO-E2,KO-E24 phase group mice serum LDH activity was significantly and significantly higher than WT-E0(P<0.01),WT-E2(P<0.01)and WT-E24(P<0.05)phase group;the changes of SOD,MDA and SOD/MDA levels in skeletal muscle of mice did not differ between the two genotype groups;endoplasmic reticulum stress-related protein expression In addition,the expression of GRP78 in skeletal muscle of KO-E24 phase group was significantlyhigher than that in WT-E24 phase group(P<0.01),and the expression of Caspase12 in skeletal muscle of KO-E2 and KO-E24 group was significantly higher than that of WT-E2,WT-E24 phase group(P<0.05);in the ultrastructural observation of skeletal muscle,the ultrastructure of skeletal muscle was significantly changed in each phase of KO and WT movement compared with the quiet control group,and the change had Delayed characteristics,skeletal muscle appears irregular arrangement of myofibrillar fibers,Z-line distortion becomes shallow,light and dark bands are not clear,interstitial edema,endoplasmic reticulum,mitochondria and other organelle structures Often,especially in 24 hours and 48 hour group most obvious,but mice WT KO mice compared with the extent of damage in skeletal muscle ultrastructure of small,fast recovery time.Conclusion: Exercise induces endoplasmic reticulum stress response in skeletal muscle of mice.MG53 protein knockout exacerbates the structural damage of mouse skeletal muscle cells induced by exercise,and the imbalance of myocyte homeostasis leads to the change of endoplasmic reticulum stress duration.Long and endoplasmic reticulum stress intensity increases and muscle cells have a tendency to apoptosis.