The Study On The Difference Of Pathogenic Mechanism And Characteristics Of Endoplasmic Reticulum Stress-mediated Apoptosis In Different Age Rats With Crush Syndrome

ObjectiveCrush syndrome is the second leading cause of death after earthquake,in addition to direct traumatic death.So for,there is no study on the relationship between age and the pathogenesis of crush syndrome.This study will focus on the pathophysiological characteristics of the crush syndrome in different age rats,and the pathogenicity and mechanism of apoptosis mediated by endoplasmic reticulum stress in the crush syndrome in different week-old rats.MethodsThere were 144 healthy male Wistar rats with different weeks of age,48 of which were child,adult and elderly rats respectively.Each age group was randomly divided into control group(n = 16),12 h group(n = 16)and 72 h group(n = 16).The rats were pressed at the pressure of 15 times their own body weight on the muscles of the lower limbs to create CS models.After 16 h of compression and 12 h or 72 h of decompression,survival rates were recorded.The serum biochemical indexes,IL-6,IL-10,TNF-α,High Mobility Group Box 1(HMGB1),myoglobin(Mb)and renal tissue Mb contents were measured.Tissue samples were evaluated by histopathological analysis.TUNEL staining was performed on the compressed muscle tissue and renal tissue to observe apoptosis.Apoptotic and endoplasmic reticulum stress-related protein expression was detected by immunohistochemistry.The control group was not treated while the sampling method was the same as the CS model group.ResultsThe survival rates of different age groups were different.The survival rate of the elderly group was the lowest(50%,8/16),while that of the adult group was 75%(12/16)and the child group was the highest(93.75%,15/16).The levels of serum K+,CK,BUN,Cr,ALT,AST,LDH,IL-6,IL-10,TNF-α,serum and renal myoglobin were significantly increased in the model group rats.Compared with child and adult model rats,the elderly group rats have the biggest changes in most of these indicators.Pathological result showed that the muscles,kidneys and lungs of all age groups rats showed varying degrees of injury.The pathological damage was most severe in elderly model rats.The degree of renal tissue damage in the child group was lower than that in the adult and elderly groups.The ratio of apoptotic cells,and the expressions of Caspase-3,Caspase-12,CHOP in renal and muscle tissue of rats in model group were significantly higher than those in control group(P <0.01).The expression changes vary with the age of the rat.The elderly rats had the highest expression level.Conclusions1.Age is an independent risk factor for the occurrence of crush syndrome,which is closely related to the development and prognosis of disease.The degree of injury,pathogenesis,pathophysiological characteristics and prognosis of crush syndrome in different week-old rats is not the same.2.After decompression,the content of renal Mb and the degree of damage of renal tissue in the child group were lower than that of the adult group and the elderly group.The degree of damage of renal tissue was most significant in the elderly group.3.The degree of apoptosis of renal tubular epithelial cell mediated by endoplasmic reticulum stress in different age rats is not the same.The ER stress-mediated apoptosis in the elderly group was the most significant,and the ER stress-mediated apoptosis in the child group was lower than that in the adult group and the elderly group.4.Inflammation and HMGB1 expression may participate in the activation of endoplasmic reticulum stress and apoptosis.5.This study provides strategies and experimental evidence for the individualized treatment of crush syndrome in different ages.