人脐带间充质干细胞对新生大鼠脑白质损伤后水通道蛋白4的影响

doi:10.3969/j.issn.1006-5725.2026.08.002

Abstract

Abstract:

Objective To observe the effect of human umbilical cord mesenchymal stem cells （HUC-MSCs） transplantation on aquaporin-4（AQP4）after white matter injury（WMI）in neonatal rats，and to evaluate the repair effect on blood-brain barrier and its possible mechanism. Methods A total of 90 2-day-old Sprague-Dawley（SD）rats were randomly divided into three groups：the sham operation group，the WMI group，and the HUC-MSCs group，with 30 rats in each group.The WMI model of neonatal rats was constructed by intraperitoneal injection of low dose lipopolysaccharide（0.05 mg/kg），unilateral common carotid artery ligation combined with hypoxia（8% oxygen + 92% nitrogen）.The HUC-MSCs group was transplanted with 2×10⁵ HUC-MSCs at a dose of 2 μL by a brain stereotaxic apparatus within 2 hours after modeling.Samples were collected and tested at different time points after modeling.The brain water content of rats in each group was detected by wet and dry weight measurement；The pathological changes of brain tissue in each group were observed by hematoxylin-eosin staining； Immunohistochemical staining was used to observe the expression sites and levels of glial fibrillary acidic protein （GFAP）， AQP4 and myelin basic protein （MBP） in brain tissues，the expression levels of AQP4，GFAP and MBP protein in each group were detected by Weston blot，the memory and spatial exploration ability of rats in each group were observed by Morris water maze test，and the concentration of Evans blue in each group was detected by Evans blue test. Results Compared with the sham operation group，the WMI group showed loose nerve fiber arrangement，disordered shape，nuclear pyknosis and nuclear lysis. The situation in the HUC-MSCs group was improved compared with the WMI group. Compared with the sham group， the brain water content in the WMI group increased （all P < 0.05）； Brain water content decreased in the HUC-MSCs group compared with the WMI group （all P < 0.05）. Compared with the sham group， the content of Evans blue in the brain tissue of the WMI group and the HUC-MSCs group increased， and decreased in the HUC-MSCs group compared with the WMI group （all P < 0.05）. The expression of MBP in the WMI group and HUC-MSCs group decreased compared with the sham group， which increased in the HUC-MSCs group compared with the WMI group （all P < 0.05）. And the expression of GFAP in the WMI group and HUC-MSCs group increased compared with the sham group， and it decreased in the HUC-MSCs group compared with the WMI group （all P < 0.05）. AQP4 had the same trend as GFAP （all P < 0.05）. The escape incubation period of WMI group and HUC-MSCs group was prolonged， the number of platforms crossed and the time stayed in the target quadrant were shortened compared with the sham group； and the escape incubation period was shortened， the number of platforms crossed and the time spent in the target quadrant increased in the HUC-MSCs group compared with the WMI group（all P < 0.05）. Conclusion HUC-MSCs have a certain repair effect on WMI blood-brain barrier in neonatal rats， and the mechanism may be related to the inhibition of astrocyte activation and down-regulation AQP4 protein expression.

Key words: white matter injury, human umbilical cord mesenchymal stem cells, blood-brain barrier, astrocytes, aquaporin-4

CLC Number:

R722

Yameng LIU,Chao WANG,Mengxin WANG,Shanning GAN,Yanping ZHU. Effects of human umbilical cord mesenchymal stem cells on aquaporin-4 after white matter injury in neonatal rats[J]. The Journal of Practical Medicine, 2026, 42(8): 1312-1321.

Figures/Tables 8

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References 38

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组别	脑含水量
组别	7 d	14 d	t值	P值
假手术组	85.74 ± 0.18	82.81 ± 0.18	28.339	< 0.001
WMI组	86.40 ± 0.25^*	83.94 ± 0.27^*	16.172	< 0.001
HUC-MSCs组	85.76 ± 0.50^#	82.91 ± 0.13^#	13.492	< 0.001
F值	7.235	56.961
P值	0.006	< 0.001

组别	MBP		GFAP		AQP4
组别	平均光密度值	相对蛋白表达量	平均光密度值	相对蛋白表达量	平均光密度值	相对蛋白表达量
假手术组	0.22 ± 0.01	1.27 ± 0.11	0.17 ± 0.01	0.82 ± 0.08	0.16 ± 0.02	0.82 ± 0.09
WMI组	0.16 ± 0.00^*	0.76 ± 0.07^*	0.26 ± 0.02^*	1.19 ± 0.09^*	0.24 ± 0.17^*	1.18 ± 0.10^*
HUC-MSCs组	0.20 ± 0.01^*#	1.01 ± 0.08^*#	0.23 ± 0.02^*#	1.01 ± 0.04^*#	0.20 ± 0.01^*#	0.99 ± 0.04^*#
F值	106.690	46.550	42.125	37.641	48.215	29.828
P值	< 0.001	< 0.001	< 0.001	< 0.001	< 0.001	< 0.001

组别	逃逸潜伏期/s					穿越平台次数	目标象限停留时间/s
组别	DAY1	DAY2	DAY3	DAY4	DAY5	穿越平台次数	目标象限停留时间/s
假手术组	53.82 ± 3.34	43.11 ± 2.06	36.87 ± 3.10	23.53 ± 2.11	9.06 ± 2.36	8.33 ± 1.75	48.60 ± 3.63
WMI组	51.39 ± 6.47	52.44 ± 4.54^*	46.13 ± 5.05^*	35.89 ± 1.82^*	21.47 ± 5.80^*	4.83 ± 0.75^*	35.32 ± 3.03^*
HUC-MSCs组	54.58 ± 3.98	47.12 ± 2.18^*#	41.46 ± 2.07^*#	28.96 ± 1.26^*#	14.85 ± 2.13^*#	6.67 ± 0.82^*#	42.08 ± 5.90^*#
F值	0.723	13.292	9.789	85.813	15.876	12.830	13.880
P值	0.501	< 0.001	0.002	< 0.001	< 0.001	0.001	< 0.001

Effects of human umbilical cord mesenchymal stem cells on aquaporin-4 after white matter injury in neonatal rats

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