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人脐带间充质干细胞通过 p38 丝裂原活化蛋白激酶/核因子-κB 通路促进急性脊髓损伤后膀胱功能的重建。

Human umbilical cord mesenchymal stem cells contribute to the reconstruction of bladder function after acute spinal cord injury via p38 mitogen-activated protein kinase/nuclear factor-kappa B pathway.

机构信息

Department of Nursing, Shenzhen Hospital, Southern Medical University, Shenzhen, Guangdong, 518101, P.R. China

School of Nursing, Southern Medical University, Guangzhou, Guangdong, 510515, P.R. China

出版信息

Bioengineered. 2022 Mar;13(3):4844-4856. doi: 10.1080/21655979.2022.2036397.

DOI:10.1080/21655979.2022.2036397
PMID:35152833
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8973731/
Abstract

The association between spinal cord injury (SCI) and bladder symptoms has been intensively described. Human umbilical cord mesenchymal stem cell (hUC-MSC) treatment is beneficial to the recovery of bladder function after SCI, but its mechanism is unclear. We established an SCI model, and prepared hUC-MSCs in advance, followed by verification using flow cytometry. The Basso, Beattie and Bresnahan (BBB) score and urodynamic index were employed to evaluate motor function and bladder functions, respectively. Hematoxylin-eosin staining, luxol fast blue staining, and Masson's trichrome staining were utilized to assess pathological changes. Real-time quantitative PCR and Western blot were used to determine the mRNA and protein expressions in bladder tissues. The immunophenotypes of the HUC-MSCs were CD90 and CD105, but CD34, CD45 and HLA-DR. Rats appeared severe motor dysfunction after SCI, but the BBB score was increased in hUC-MSCs after the second week. Pathologically, the improvement of the lesion area on the dorsal spinal cord, augmented anterior gray horn neuron cells of the spinal cord and lessened bladder tissue remodeling (fibrosis, collagen deposition) as well as modulated inflammation could be observed. Besides, SCI increased bladder weight, bladder capacity, urine volume and residual urine volume, and decreased urination efficiency. HUC-MSCs ameliorated SCI-induced pathological changes and bladder functions, the expressions of Collagen I, Collagen III, fibroblast growth factor 2 (FGF2), phospho-p38, transient receptor potential vanilloid 1, Toll-like receptor 4 and phospho-nuclear factor-kappa B (p-NF-κB). To sum up, HUC-MSCs contribute to the reconstruction of bladder function after SCI by repressing p38 MAPK/NF-κB pathway.

摘要

脊髓损伤(SCI)与膀胱症状之间的关联已得到深入描述。人脐带间充质干细胞(hUC-MSC)治疗有益于 SCI 后膀胱功能的恢复,但其机制尚不清楚。我们建立了 SCI 模型,并事先准备 hUC-MSCs,然后通过流式细胞术进行验证。Basso、Beattie 和 Bresnahan(BBB)评分和尿动力学指标分别用于评估运动功能和膀胱功能。苏木精-伊红染色、卢索快速蓝染色和 Masson 三色染色用于评估病理变化。实时定量 PCR 和 Western blot 用于检测膀胱组织中的 mRNA 和蛋白表达。HUC-MSCs 的免疫表型为 CD90 和 CD105,但 CD34、CD45 和 HLA-DR。大鼠 SCI 后出现严重的运动功能障碍,但 hUC-MSCs 治疗后第二周 BBB 评分增加。病理上,观察到背侧脊髓损伤部位的病变面积改善,脊髓前角灰质神经元细胞增多,膀胱组织重构(纤维化、胶原沉积)减轻,炎症得到调节。此外,SCI 增加了膀胱重量、膀胱容量、尿量和残余尿量,降低了排尿效率。HUC-MSCs 改善了 SCI 引起的病理变化和膀胱功能,下调了 Collagen I、Collagen III、成纤维细胞生长因子 2(FGF2)、磷酸化 p38、瞬时受体电位香草酸 1、Toll 样受体 4 和磷酸化核因子-κB(p-NF-κB)的表达。总之,HUC-MSCs 通过抑制 p38 MAPK/NF-κB 通路有助于 SCI 后膀胱功能的重建。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2f33/8973731/312190339d90/KBIE_A_2036397_F0005_OC.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2f33/8973731/0ceedbdd2462/KBIE_A_2036397_UF0001_OC.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2f33/8973731/353ad66278b3/KBIE_A_2036397_F0002_OC.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2f33/8973731/2453aaa9074a/KBIE_A_2036397_F0003_OC.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2f33/8973731/2d80ae33b797/KBIE_A_2036397_F0004_OC.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2f33/8973731/312190339d90/KBIE_A_2036397_F0005_OC.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2f33/8973731/0ceedbdd2462/KBIE_A_2036397_UF0001_OC.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2f33/8973731/7e29e465a77c/KBIE_A_2036397_F0001_OC.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2f33/8973731/353ad66278b3/KBIE_A_2036397_F0002_OC.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2f33/8973731/2453aaa9074a/KBIE_A_2036397_F0003_OC.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2f33/8973731/2d80ae33b797/KBIE_A_2036397_F0004_OC.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2f33/8973731/312190339d90/KBIE_A_2036397_F0005_OC.jpg

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