中国临床药理学杂志

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

PDF下载

邢二庆 ^1a , 张玉 ^1b , 尚家星 ^1c , 王成祥 ^1a , 谢遂亮 ^1a , 王向华 ^1a , 豆文婷 ^1a

中国临床药理学杂志 | 临床与基础桥接研究 2025,41(4): 512-516

收起

中国临床药理学杂志 |临床与基础桥接研究 2025 , 41 (4) : 512 -516

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

全屏

邢二庆^1a, 张玉^1b, 尚家星^1c, 王成祥^1a, 谢遂亮^1a, 王向华^1a, 豆文婷^1a

作者信息

^1a.新乡市中心医院（新乡医学院第四临床学院），儿科一病区，河南新乡 453000

^1b.新乡市中心医院（新乡医学院第四临床学院），儿科、新生儿科东区，河南新乡 453000

^1c.新乡市中心医院（新乡医学院第四临床学院），心血管内科，河南新乡 453000

通讯作者:

张玉，副主任医师 MP: 15836043975 E-mail: cute_zhangyu@163.com

作者简介:

邢二庆（1985-），女，主治医师，主要从事小儿肾病方面临床诊疗的工作和相关研究

Monosialotetrahexosylganglioside protects brain injury in neonatal rats based on the UCH-L1/BDNF pathway

Er-qing XING^1a, Yu ZHANG^1b, Jia-xing SHANG^1c, Cheng-xiang WANG^1a, Sui-liang XIE^1a, Xiang-hua WANG^1a, Wen-ting DOU^1a

Affiliations

^1a.Pediatric Ward 1, Xinxiang Central Hospital (The Fourth Clinical College of Xinxiang Medical College), Xinxiang 453000, Henan Province, China

^1b.Pediatrics, Neonatology Eastern, Xinxiang Central Hospital (The Fourth Clinical College of Xinxiang Medical College), Xinxiang 453000, Henan Province, China

^1c.Cardiovascular Medicine, Xinxiang Central Hospital (The Fourth Clinical College of Xinxiang Medical College), Xinxiang 453000, Henan Province, China

出版时间: 2025-02-28 doi: 10.13699/j.cnki.1001-6821.2025.04.013

文章导航

摘要

收起

目的

基于泛素羧基末端水解酶-1（UCH-L1）/脑源性神经营养因子（BDNF）信号通路探讨单唾液酸四己糖神经节苷脂（GM1）对新生大鼠缺氧缺血性脑损伤（HIBD）的保护作用。

方法

将20日龄SD大鼠随机分为模型组、假手术组和实验组，每组10只。模型组和实验组大鼠均结扎左侧颈总动脉，置于一定氧氮比（8∶92）的缺氧箱内2 h构建HIBD模型。模型构建成功后，实验组腹腔注射20 mg·kg^-1·d^-1 GM1，模型组和假手术组均腹腔注射0.9% NaCl（0.25 mL·kg^-1）。用改良神经系统严重程度评分（modified neurological severity score，mNSS）评估神经损伤程度，用2，3，5-氯化三苯基四氮唑染色法检测脑梗死情况，用干湿重法测定脑含水量，用Morris水迷宫实验评估认知能力，用原位末端转移酶标记法检测细胞凋亡，用酶联免疫吸附试验法检测炎症因子水平，用蛋白质印迹法检测UCH-L1和BDNF蛋白相对表达水平。

结果

假手术组、模型组和实验组的mNSS评分分别为（0.10±0.02）、（2.60±0.45）和（1.50±0.20）分，脑梗死率分别为（0.89±0.11）%、（32.56±4.12）%和（18.56±2.52）%，脑含水量分别为（68.25±7.05）%、（88.87±9.26）%和（71.11±8.11）%，潜伏期分别为（22.60±2.86）、（38.60±4.11）和（25.50±3.33）s，平台停留时间分别为（125.50±17.68）、（80.60±9.68）和（115.80±13.89）s，穿越平台次数分别为（2.80±0.35）、（0.70±0.09）和（1.80±0.30）次，凋亡率分别为（6.65±0.74）%、（21.88±3.05）%和（13.62±2.62）%，肿瘤坏死因子-α水平分别为（30.05±3.85）、（121.61±18.85）和（82.14±11.65）pg·mL^-1，白细胞介素-1β水平分别为（92.55±12.15）、（321.25±41.24）和（212.32±25.61）pg·mL^-1，白细胞介素-6水平分别为（184.32±20.54）、（275.62±31.12）和（208.65±22.65）pg·mL^-1，UCH-L1蛋白相对表达水平分别为1.00±0.22、1.75±0.34和1.40±0.28，BDNF蛋白相对表达水平分别为1.00±0.21、1.68±0.38和2.54±0.41。假手术组的上述指标与模型组比较，在统计学上差异均有统计学意义（P<0.01，P<0.001）；模型组的上述指标与实验组比较，在统计学上差异均有统计学意义（P<0.05，P<0.001）。

结论

GM1可通过激活UCH-L1/BDNF信号通路改善神经细胞凋亡与炎性反应，发挥对新生大鼠HIBD的保护作用。

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

Abstract

收起

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-α levels 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.

Key words

monosialotetrahexosylganglioside / ubiquitin carboxy-terminal hydrolase 1 / brain-derived neurotrophic factor / hypoxic ischemic brain injury / nerve cell / neonatal rat

引用本文

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. 中国临床药理学杂志, 2025 , 41 (4) : 512 -516 . DOI: 10.13699/j.cnki.1001-6821.2025.04.013

Er-qing XING, Yu ZHANG, Jia-xing SHANG, Cheng-xiang WANG, Sui-liang XIE, Xiang-hua WANG, Wen-ting DOU. Monosialotetrahexosylganglioside protects brain injury in neonatal rats based on the UCH-L1/BDNF pathway[J]. Chinese Journal of Clinical Pharmacology, 2025 , 41 (4) : 512 -516 . DOI: 10.13699/j.cnki.1001-6821.2025.04.013

基金

收起

河南省医学科技攻关计划基金资助项目(SB201904015)

参考文献

收起

文献

收起

参考文献引证文献

排序方式：

2025年第41卷第4期

PDF下载

引用本文

BibTeX

文章信息

doi: 10.13699/j.cnki.1001-6821.2025.04.013

接收时间：2024-09-20
首发时间：2026-08-04
出版时间：2025-02-28

补充材料

相关文章

文章信息

作者

出版历史

收稿日期：2024-09-20

基金

河南省医学科技攻关计划基金资助项目(SB201904015)

作者信息

^1a.新乡市中心医院（新乡医学院第四临床学院），儿科一病区，河南新乡 453000

^1b.新乡市中心医院（新乡医学院第四临床学院），儿科、新生儿科东区，河南新乡 453000

^1c.新乡市中心医院（新乡医学院第四临床学院），心血管内科，河南新乡 453000

通讯作者:

张玉，副主任医师 MP: 15836043975 E-mail: cute_zhangyu@163.com

参考文献

分享链接

https://castjournals.cast.org.cn/joweb/zglcylxzz/CN/10.13699/j.cnki.1001-6821.2025.04.013

分享至

全文二维码

扫描看全文

引用本文

BibTeX

本文的引用情况

2种不同金属材料的力学参数

科 Family	属数 Number of genus	种数 Number of species	占总种数比例 Percentage of total species (%)	属 Genus	种数 Number of species	占总种数比例 Percentage of total species (%)
鹅膏菌科Amanitaceae	2	11	5.26	鹅膏菌属 Amanita	10	4.78
小菇科 Mycenaceae	2	12	5.74	丝盖伞属 Inocybe	5	2.39
多孔菌科 Polyporaceae	8	14	6.70	蜡蘑属 Laccaria	5	2.39
红菇科 Russulaceae	3	23	11.00	小皮伞属 Marasmius	6	2.87
				小菇属 Mycena	11	5.26
				光柄菇属 Pluteus	5	2.39
				红菇属 Russula	17	8.13
				栓菌属 Trametes	5	2.39

关闭全屏

BibTeX
EndNote
RefWorks
TxT