Study Of The Calcium Sensing Receptor In Apoptosis Of Nerve Cell After Traumatic Brain Injury In Rats

Objective: To investigate the expression of calcium-sensing receptor(Ca SR)in neurons after traumatic brain injury(TBI).Analyzing the change of the expression of Ca SR and Caspase-3 with the relationship between the neuronal apoptosis.Methods: Fifty-four healthy male SD rats were randomly divided into three groups: the normal matched group,TBI group and inhibitor group(n=18),the each group was divided into 3 subgroups: 6 hours,24 hours,and 72 hours(n=6).TBI animal models of the TBI groups and inhibitor groups were established using Feeney's method,Ca SR antagonist NPS2390(1.5mg/kg)was infused caudal vein for 2 days before the establishment of the inhibitor groups.Modified Neurological Severity Scores(m NSS)was used to evaluate the neural behavior of rats in each group.Real-Time PCR was used to detect Ca SR,Caspase-3 m RNA expression.Western blot was used to detect Ca SR,Caspase-3 protein expression.Tunel assay was used to detect neuronal apoptosis.The data were analyzed by one way ANOVA analysis.Results :(1)HE staining observed a large number of red cell accumulation in subarachnoid space.(2)The results showed that the neurobehavioral scores of TBI group compared with the control group and inhibitor group increased in 6h,24 h,72h after modeling m NSS score(P<0.01).(3)The show of Real-Time PCR transcription and Western blotting protein in each group: TBI group compared with the inhibitor group and control group,the expression of Ca SR and Caspase-3 were increased and decreased expression in inhibitor groups,reached the peak value at 24h(P<0.01).Compared with the control group and the inhibitor group,the expression of Ca SR m RNA and its protein were increased in the TBI group(P<0.01).The expression of Caspase-3 were higher than that of the control group and the inhibitor group in 24h(P<0.05).(4)The results of TUNEL assay showed that the 24 h apoptotic cells reached the peak value after the TBI model was made(P<0.05).The TBI group compared inhibitor group and control group,the number of apoptotic cells were significantly increased(P<0.01).(5)There was a positive correlation between Ca SR western-blot and Caspase-3 western-blot and neuronal apoptosis(r=0.300,r=0.371,P<0.05).Ca SR and Caspase-3 western-blot were both found to have a positive correlation(r=3.434,P<0.01).There was a positive correlation between Ca SR m RNA and Caspase-3 m RNA and neuronal apoptosis(r=0.300,r=0.371,P<0.05).Ca SR and Caspase-3 m RNA were both found to have a positive correlation(r=3.434,P<0.01).Conclusion : In traumatic brain injury,the expression of Ca SR is signif icantly increased in brain injury.Ca SR antagonist NPS2390 could down-regulate the expression of Ca SR,improve neurobehavioral scores,and reduce apoptosis.It expression is involved in the development of traumatic brain injury.