Impact of Curcumin Regulating BDNF/TrkB Signaling Pathway on Neuronal Apoptosis in Neonatal Rat with Bacterial Meningitis
Objective:To investigate the impact of curcumin(Cur)regulating the brain-derived neurotrophic factor(BDNF)/tropomyosin related kinase B receptor(TrkB)signaling pathway on neuronal apoptosis in neonatal rat with bacterial meningitis(BM).Methods:15 rats were randomly selected as non-infected group(NF group),other rats injected streptococcus pneumoniae ATCC49619 suspension into frontal subarachnoid space to construct BM rat model,the successful BM model was randomly divided into BM group,L-Cur group(1.25 mg/kg),M-Cur group(2.5 mg/kg),H-Cur group(5 mg/kg),H-Cur+K252a group(5 mg/kg Cur+2.5 μg/kg K252a),15 rats in each group,once a day,the injections were given continuously for 3 weeks.The rats were weighed and clinical scored,HE staining and Nissl staining were used to observe the damage of nerve cells;TUNEL staining was used to evaluate neuronal apoptosis.The levels of glial fibrillary acid protein(GFAP)and spinal cord calcium ion adaptor protein-1(IBA-1)were detected by immunofluorescence staining.The levels of inflammatory factors and chemokines in brain tissue were detected by real-time fluorescence quantitative polymerase chain reaction(qRT-PCR).Western blot was used to detect the expression of apoptosis protein and BDNF/TrkB pathway protein in brain tissue.Results:The brain tissue structure of the NF group was normal,large area of blue Nissl bodies appeared in the cytoplasm of neurons.In the BM group,a large amount of inflammatory exudate and inflammatory cell infiltration appeared in the subarachnoid space,the cell bodies were enlarged,the processes contracted,and the morphology was irregular;the number of Nissl bodies,weight,the levels of Bcl-2,BDNF,and p-TrkB/TrkB protein decreased obviously(P＜0.05),the clinical score,the relative fluorescence intensity values of IBA-1 and GFAP,the relative expression of chemokine ligand-2(CCL-2),chemokine ligand-3(CCL-3),tumor necrosis factor-α(TNF-α),interleukin-6(IL-6),the rate of neuronal apoptosis,and the level of BCL2-Associated X protein(Bax)protein increased obviously(P＜0.05).The inflammatory exudate and cell infiltration of brain tissue were reduced,the number of Nissl bodies,weight,the levels of B-lymphoblastoma-2 gene(Bcl-2),BDNF,and p-TrkB/TrkB protein increased obviously in each group after Cur treatment(P＜0.05),the clinical score,the relative fluorescence intensity values of IBA-1 and GFAP,the relative expression of CCL-2,CCL-3,TNF-α,and IL-6,the rate of neuronal apoptosis,and the level of Bax protein decreased obviously(P＜0.05),the higher the addition dose of Cur,the more obvious the change;the effect of H-Cur+K252a group was similar to that of BM group,K252a reversed the improvement effects of Cur on neuron apoptosis and damage in BM rat.Conclusion:Cur might reduced neuronal apoptosis in BM rat by activating BDNF/TrkB signaling pathway.
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