中国临床药理学杂志2025，Vol.41Issue(4)：512-516,5.DOI:10.13699/j.cnki.1001-6821.2025.04.013
单唾液酸四己糖神经节苷脂基于UCH-L1/BDNF通路保护新生大鼠脑损伤
Monosialotetrahexosylganglioside protects brain injury in neonatal rats based on the UCH-L1/BDNF pathway
摘要
Abstract
Objective To investigate the protective effects of monosialotetrahexosylganglioside(GM1)on hypoxic-ischemic brain damage(HIBD)in neonatal rats based on the ubiquitin C-terminal hydrolase L1(UCH-L1)/brain-derived neurotrophic factor(BDNF)signaling pathway.Methods Twenty-day-old SD rats were randomly divided into model group,sham group and experimental group,with 10 rats in each group.Rats in model group and experimental group were lapped with left common carotid artery and placed in anoxic chamber with a certain oxygen to nitrogen ratio(8∶92)for 2 h to construct HIBD model.After the successful construction of the model,the experimental group was intraperitoneally injected with 20 mg·kg-1·d-1GM1,and the model group and sham group were injected with 0.9％NaCl(0.25 mL·kg-1).The modified neurological severity score(mNSS)was used to evaluate the degree of neurological damage in the treated rats.Cerebral infarction was detected by 2,3,5-triphenyte-trazoliumchloride staining method;cerebral water content was determined by wet and dry weight method;cognitive ability was assessed by Morris water maze test;apoptosis was detected by terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling;inflammatory factors were detected by enzyme-linked immunosorbent assay;UCH-L1 and BDNF protein levels were detected by Western blot.Results After different treatments,the mNSS scores of sham group,model group and experimental group were(0.10±0.02),(2.60±0.45)and(1.50±0.20)points;the cerebral infarction rates were(0.89±0.11)％,(32.56±4.12)％and(18.56±2.52)％;the cerebral water content were(68.25±7.05)％,(88.87±9.26)％and(71.11±8.11)％;the latent period were(22.60±2.86),(38.60±4.11)and(25.50±3.33)s;the platform residence time were(125.50±17.68),(80.60±9.68)and(115.80±13.89)s;the platform crossing times were(2.80±0.35),(0.70±0.09)and(1.80±0.30)times;the apoptosis rates were(6.65±0.74)％,(21.88±3.05)％and(13.62±2.62)％;the tumor necrosis factor-αlevels were(30.05±3.85),(121.61±18.85)and(82.14±11.65)pg·mL-1;the levels of interleukin-1 beta were(92.55±12.15),(321.25±41.24)and(212.32±25.61)pg·mL-1;interleukin-6 levels were(184.32±20.54),(275.62±31.12)and(208.65±22.65)pg·mL-1;UCH-L1 protein levels were 1.00±0.22,1.75±0.34 and 1.40±0.28;BDNF protein levels were 1.00±0.21,1.68±0.38 and 2.54±0.41.There were statistically significant differences between sham group and model group(P＜0.01,P＜0.001).There were statistically significant differences between model group and experimental group(P＜0.05,P＜0.001).Conclusion GM1 can improve nerve cell apoptosis and inflammatory response by activating UCH-L1/BDNF signaling pathway,and play a protective role in neonatal rat HIBD.关键词
单唾液酸四己糖神经节苷脂/泛素羧基末端水解酶-1/脑源性神经营养因子/缺氧缺血性脑损伤/神经细胞/新生鼠Key words
monosialotetrahexosylganglioside/ubiquitin carboxy-terminal hydrolase 1/brain-derived neurotrophic factor/hypoxic ischemic brain injury/nerve cell/neonatal rat分类
医药卫生引用本文复制引用
邢二庆,张玉,尚家星,王成祥,谢遂亮,王向华,豆文婷..单唾液酸四己糖神经节苷脂基于UCH-L1/BDNF通路保护新生大鼠脑损伤[J].中国临床药理学杂志,2025,41(4):512-516,5.基金项目
河南省医学科技攻关计划基金资助项目(SB201904015) （SB201904015）
