摘要
目的分析不同时间窗高压氧(HBO)联合鸢尾素治疗对缺氧缺血性脑损伤(HIBD)新生大鼠海马神经元细胞凋亡及脑源性神经营养因子(BDNF)/酪氨酸蛋白激酶B(TrkB)信号通路的影响。方法选取7日龄新生SD大鼠36只,采用随机数字表法分为H0、H1、H2、H3、H4、H5组,每组各6只,除H0组外均建立HIBD模型,其中H2、H3、H4、H5组分别在HIBD后6、24、48、72 h予以HBO联合鸢尾素治疗。分别采用苏木精-伊红染色(HE)、脱氧核糖核苷酸末端转移酶介导的缺口末端标记法(TUNEL)观察海马组织形态和神经元细胞凋亡率,采用逆转录聚合酶链反应及Western blotting法分别测定BDNF和TrkB的基因及蛋白表达水平。结果与H0组比较,其余各组海马神经元细胞受损较严重,大量神经元细胞发生凋亡,其中H1组损伤最明显;H2组神经元细胞凋亡率高于H0组,但低于H1、H3、H4、H5组;H4、H5组神经元细胞凋亡率高于H0、H2、H3组,低于H1组,差异均有统计学意义(P<0.05)。H2组BDNF和TrkB的基因及蛋白表达水平均高于H1、H3、H4、H5组(P<0.05);H4、H5组的BDNF和TrkB的基因及蛋白表达水平高于H1、H3组,低于H0组,差异均有统计学意义(P<0.05);H4、H5组的神经元细胞凋亡率、BDNF和TrkB的基因及蛋白表达水平差异无统计学意义(P>0.05)。结论HIBD发生后48 h内对大鼠予以HBO联合鸢尾素治疗有较好疗效,其中6 h内的效果最佳,能减少海马神经元细胞凋亡,可能与激活BDNF/TrkB信号通路有关。
Objective To analyze the effects of HBO combined with irisin administrated at different time windows on hippocampal neuronal apoptosis and the brain-derived neurotrophic factor(BDNF)/tyrosine protein kinase B(TrkB)signaling pathway in neonatal rats with hypoxic-ischemic brain damage(HIBD).Methods A total of 36 seven-day-old SD rats were selected and divided into six groups(H0,H1,H2,H3,H4,H5)by the random number table method,with six rats in each group.Except for the H0 group,all the rats in the other five groups were established as HIBD models,and the rats in H2,H3,H4,and H5 groups were treated with HBO combined with irisin at 6,24,48,and 72 hours after HIBD,respectively.Hematoxylin and Eosin(H&E)staining and terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling(TUNEL)assay were conducted to observe the morphology of hippocampus and the apoptosis rate of neurons,respectively.Reverse transcription-polymerase chain reaction(RT-PCR)and Western blotting were used to determine the gene and protein expression levels of BDNF and TrkB,respectively.Results Compared with the H0 group,hippocampal neurons in the other groups were more severely damaged,with a large number of neurons undergoing apoptosis.Among them,the H1 group showed the most significant damage,while the H2 group showed the least damage.The rate of neuronal apoptosis in the H2 group was higher than that in the H0 group,but lower than those in the H1,H3,H4,and H5 groups.The rates of neuronal apoptosis in the H4 and H5 groups were higher than those in the H0 and H3 groups,but lower than that in the H1 group,with statistically significant differences(P<0.05).The gene and protein expression levels of BDNF and TrkB in the H2 group were higher than those in the H1,H3,H4,and H5 groups(P<0.05).The gene and protein expression levels of BDNF and TrkB in H4 and H5 groups were higher than those in the H1 and H3 groups,but lower than that in the H0 group,with statistically significant differences(P<0.05).There was no statistically significant difference in the rate of neuronal apoptosis,gene and protein expression levels of BDNF and TrkB between the H4 and H5 groups(P>0.05).Conclusion HBO combined with irisin administrated within 48 hours after the occurrence of HIBD can achieve a good curative effect,with the best effect observed within 6 hours.It can reduce the apoptosis of hippocampal neurons,which may be related to the activation of the BDNF/TrkB signaling pathway.
作者
夏莉
栗红
阴崇娟
陈美华
张钰璇
乔震
阴怀清
Xia Li;Li Hong;Yin Chongjuan;Chen Meihua;Zhang Yuxuan;Qiao Zhen;Yin Huaiqing(Department of Pediatrics,First Hospital of Shanxi Medical University,Taiyuan 030001,China)
出处
《中华航海医学与高气压医学杂志》
CAS
CSCD
2023年第2期206-211,共6页
Chinese Journal of Nautical Medicine and Hyperbaric Medicine
基金
山西省卫生健康委科研计划项目(2022027)。
