The Effect Of P25/CDK5-HDAC1 Pathway In Neuronal Damage Induced By Benzo[a]pyrene

Objective:The expression of P25,CDK5 and HDAC1 in the central nervous system caused by benzo [a] pyrene was detected by intracerebroventricular injection of benzo [a] pyrene in SD rats.The expression of P25/CDK5-HDAC1 pathway i n benzo [a] pyrene induced neuronal damage,so as to provide a theoretical ba sis for the relationship between learning and memory impairment induced by b enzo[a]pyrene and neurodegenerative diseases.Methods:1.Toxicity: 32 SD rats were randomly divided into control group,low dose group,middle dose group and high dose group.The experimental group was treated with B(a)P 2.5 mmol / L,B[a]P 5 mmol / L and B[a]P 10 mmol / L;Control group treated with dimethyl sulfoxide,once a week,each injection of 10?L,sustained exposure to 3weeks.2.Use Y-maze test to assess the ability of different concentrations of SD rats to identify memory and reference memory.3.The experimental animals were sacrificed and the brain tissue of each group was taken and the hippocampus was free.HE staining was used to observe the morphological indexes of brain tissue injury.4.The expression of P25 / P35,CDK5 and HDAC1 were detected by SABC immunohistochemistry.5.The expression of ?-actin,P25 / P35,CDK5 and HDAC1 in brain tissue were detected by Western-blotting and the results were analyzed by gel imaging system.6.RT-PCR was used to detect the expression of GAPDH,P25 / P35,CDK5 andHDAC1.7.Data analysis with SPSS22.0 software,the results of the indicators to mean ±standard using paired t test and one-way analysis of variance analysis(ANOVA),there was significantly difference when P<0.05Results:1.Rat learning and memory ability test: Compared with the learning group,the memory loss of the 2.5 mmol / L group increased(P<0.01),and the middle dose group(5 mmol / L)and high dose group(10 mmol / L)were significantly higher than those in low dose group(P <0.05).2.In the experimental group,hematoxylin-eosin(HE)staining showed that the cells in the control group and the low dose groups did not show obvious abnormalities under the microscope.The neurons in the middle and high dose group showed obvious abnormalities For cell integrity damage(cell contour blur and cell disruption)and cell morphology irregularities.3.Immunohistochemical technique(SABC)showed that the hippocampal cells in the middle and high dose groups were sparse,loose,and unclear,the cytoplasm was yellow and the color depth was.Some of the cells were visible in the empty area.The number of P25 / P35 and CDK5-positive cells was more loose,and the number of neurons in each group was significantly different.The morphology of HDAC1-positive cells was opposite.4.The expression of P25 / P35 and CDK5 protein in SD rats exposed to benzo [a]pyrene showed an increasing trend,while the expression of HDAC1 protein showed a decreasing trend.The results of Western Blotting showed that the expression of HDAC1 protein was decreased Compared with the solvent control group was statistically significant(P <0.01,P <0.05).5.Compared with DMSO group,the expression of P25 / P35 and CDK5 gene in the exposed group showed an increasing trend,while the HDAC1 gene expression decreased(P <0.01).Conclusion:1.Intracerebroventricular injection of benzo[a]pyrene can cause pathological changes of hippocampal CA1 region,affecting its learning and memory ability,B [a]P with neurotoxicity.2.The expression of P25 / CDK5 was up-regulated and the expression of HDAC1 was decreased,which indicated that B [a] P might be the initiation of P25 /CDK5-HDAC1 signaling pathway,leading to overexpression of P25 / p53,induction of neurons Cell damage.