Differences And Significance Of Endoplasmic Reticulum Stress Induced Apoptosis Of Neurons In Different Levels Of Craniocerebral Injury

Objective: Traumatic brain injury(TBI)is a common cause of disability and death in the world.TBI can be divided into primary craniocerebral injury and secondary craniocerebral injury,and secondary craniocerebral injury is the main factor leading to disability and mortality after TBI.Secondary injury,which lasts several minutes or even months,involves reactive oxygen species(ROS)generation,inflammation,endoplasmic reticulum(ER)stress,mitochondrial dysfunction,and apoptosis.This experiment is to observe the expression of the pathway proteins related to neuronal apoptosis induced by endoplasmic reticulum(ER)stress in the brain tissue of patients with different degrees of head injury,and to explore the correlation between the expression level and the degree of head injury.To better understand the pathophysiology and molecular changes of the secondary craniocerebral injury,and provide directions for more accurate treatment in the future.Methods:1.Collect 22 brain tissue samples from patients with traumatic brain injury as the experimental group,divided into three groups according to GCS scores: moderate head injury(GCS 9-12),severe head injury(GCS 6-8),and extra severe head injury(GCS 3-5);5 normal brain tissues were used as the control group.Specimens were first placed in a 2ml refrigerated tube and immediately frozen in liquid nitrogen for 5 seconds,then stored in a-80 degree refrigerator.2.The TUNEL method(color rendering method)measures its contrast index(AI).3.Western blot method(Western blot method)to detect the protein expressions of the GRP78,p-IRE1,p-PERK,ATF6,p-JNK,ATF4,Chop,caspase3,bcl-2,Bax.Results:1.The TUNEL method detected the normal control group and different head injury groups and AI values.The AI values of the normal control group,moderate craniocerebral injury group,severe craniocerebral injury group,extra severe craniocerebral injury group were:14.738±2.852,29.473±1.156,43.435±2.521,67.905±8.370.The AI value of the brain injury group was higher than that of the normal control group(P <0.05),and the AI value of the brain injury group increased with the increase of the brain injury degree(r=0.969,P = 0.000).2.Western blot method(protein labeling method)showed that compared with the normal control group,in the brain injury group,the expressions of the initial proteins GRP78,p-IRE1,p-PERK,and ATF6 increased(P<0.05);the expression of the key pathway proteins ATF4,p-JNK and Chop increased(P<0.05);the expression of the apoptosis protein Bax increased(P<0.05);the expression of inhibitor apoptosis protein bcl-2 decreased(P<0.05);the expression of execute apoptosis protein caspase3 increased(P<0.05).In the craniocerebral injury group,with the degree of the brain injury increased,the expression of the initial proteins GRP78,p-IRE1,p-PERK,and ATF6 increased(P <0.05);the expressions of the key pathway proteins ATF4,p-JNK,and Chop increased.the expression of the apoptosis protein Bax increased(P <0.05);the expression of inhibitor apoptosis protein bcl-2 decreased(P <0.05);the expression of execute apoptosis protein caspase3 increased(P <0.05).Conclusions:1.The apoptotic index(AI)value of the experimental group of head injury was higher than that of the normal control group.In the experimental group: the AI value of the moderate craniocerebral injury group,severe craniocerebral injury group,extra severe craniocerebral injury group gradually increased.This indicates that apoptosis occurred after craniocerebral injury,and the degree of apoptosis may be positively correlated with the severity of craniocerebral injury.2.Compared with the control group,The expression of the experimental group's endoplasmic reticulum stress-dependent apoptosis pathway-related proteins:the GRP78,p-IRE1,p-PERK,ATF6,ATF4,p-JNK,Chop,pro-apoptotic protein Bax,and execute apoptosis protein caspase3 increased,while the inhibitor apoptosis protein bcl-2 decreased.This shows that endoplasmic reticulum stress-induced apoptosis may be initiated and executed in craniocerebral injury.3.In the experimental group: moderate craniocerebral injury group,severe craniocerebral injury group,extra severe craniocerebral injury group endoplasmic reticulum stress-dependent apoptosis pathway-related proteins: the GRP78,p-IRE1,p-PERK,ATF6,ATF4,p-JNK,Chop,proapoptotic protein Bax,and executive apoptotic protein caspase3 showed an increasing trend,while apoptotic protein bcl-2 showed a decreasing trend.This shows that endoplasmic reticulum stress-induced apoptosis may be positively correlated with the degree of the brain.4.The increase of the apoptosis index and the expression of related proteins caused by endoplasmic reticulum stress in the brain injury group,this indicates that the endoplasmic reticulum stress response is involved in the physiological mechanism of post-traumatic brain injury,which provides a basis for guiding the precise treatment of clinical secondary brain injury.