Zhang Qingping, Zhang Shitao, Chen Hongquan, Chen Gang, Cui Chunhong, Zhang Junxin, Wang Weiming, Zhang Qinghua, Guo Shiwen
Department of Neurosurgery, The First Affiliated Hospital of Xi'an Jiaotong University, No. 277 Xi'an Yanta West Road, Xi'an, 710061, Shaanxi, China.
Department of Neurosurgery, The 6th Affiliated Hospital of Shenzhen University Medical School (Shenzhen Nanshan People's Hospital), No. 89 Taoyuan Road, Nanshan District, Shenzhen, 518052, Guangdong, China.
Mol Neurobiol. 2023 May;60(5):2632-2643. doi: 10.1007/s12035-023-03208-y. Epub 2023 Jan 24.
Mucosa-associated lymphoid tissue lymphoma translocation protein 1 (MALT1) is involved in neural injury, neuroinflammation, microglia activation, and polarization, while its function in spinal cord injury (SCI) remains unclear. Thus, this study aimed to evaluate the role of MALT1 modification on SCI recovery and its underlying mechanism. SCI surgery or sham surgery was performed in Sprague-Dawley rats. Then, MALT1 knockdown or negative control lentivirus was injected into SCI rats. Subsequently, MALT1 expression, locomotor capability, neural injury, markers for microglia activation and polarization, inflammatory cytokine expressions, and nuclear factor (NF)-κB pathway were detected. SCI rats exhibited higher MALT1 expression, microglia activation and M1 polarization, neuroinflammation, and NF-κB pathway activation, while worse locomotor capacity compared to sham rats (all P < 0.05). In SCI rats, MALT1 knockdown alleviated Basso, Beattie, and Bresnahan score from 10 to 28 days and attenuated HE staining reflected neural injury (all P < 0.05). Besides, MALT1 knockdown declined the number of IBA1 cells, IBA1 iNOS cells, and IBA1 CD86 cells, while enhanced the number of IBA1 Arg1 cells and IBA1 CD206 cells in SCI rats (all P < 0.05). Meanwhile, MALT1 knockdown declined the expressions of IL-1β, IL-6, and TNF-α in SCI (all P < 0.05), but did not affect IL-10 expression (P > 0.05). Furthermore, MALT1 knockdown suppressed NF-κB pathway activation validated by immunofluorescence staining and western blot assays (all P < 0.05). MALT1 knockdown improves functional recovery, attenuates microglia activation, M1 polarization, and neuroinflammation via inhibiting NF-κB pathway in SCI.
黏膜相关淋巴组织淋巴瘤易位蛋白1（MALT1）参与神经损伤、神经炎症、小胶质细胞激活和极化，但其在脊髓损伤（SCI）中的作用仍不清楚。因此，本研究旨在评估MALT1修饰对SCI恢复的作用及其潜在机制。对Sprague-Dawley大鼠进行SCI手术或假手术。然后，将MALT1基因敲低或阴性对照慢病毒注入SCI大鼠体内。随后，检测MALT1表达、运动能力、神经损伤、小胶质细胞激活和极化标志物、炎性细胞因子表达以及核因子（NF）-κB通路。与假手术大鼠相比，SCI大鼠表现出更高的MALT1表达、小胶质细胞激活和M1极化、神经炎症以及NF-κB通路激活，而运动能力更差（所有P<0.05）。在SCI大鼠中，MALT1基因敲低在10至28天减轻了Basso、Beattie和Bresnahan评分，并减轻了HE染色反映的神经损伤（所有P<0.05）。此外，MALT1基因敲低减少了SCI大鼠中IBA1细胞、IBA1 iNOS细胞和IBA1 CD86细胞的数量，同时增加了IBA1 Arg1细胞和IBA1 CD206细胞的数量（所有P<0.05）。同时，MALT1基因敲低降低了SCI中IL-1β、IL-6和TNF-α的表达（所有P<0.05），但不影响IL-10表达（P>0.05）。此外，通过免疫荧光染色和蛋白质印迹分析验证，MALT1基因敲低抑制了NF-κB通路激活（所有P<0.05）。MALT1基因敲低通过抑制SCI中的NF-κB通路改善功能恢复，减轻小胶质细胞激活、M1极化和神经炎症。
