共 48 条
Duraplasty of PHBV/PLA/Col membranes promotes axonal regeneration by inhibiting NLRP3 complex and M1 macrophage polarization in rats with spinal cord injury
被引:13
作者:
Zhao, Tengfei
[1
]
Xu, Kan
[1
]
Wu, Qionghua
[1
]
Wang, Chenggui
[1
]
Xiao, Shining
[1
]
Li, Heyangzi
[2
,3
]
He, Teng
[2
,3
]
Wang, Linlin
[2
,3
]
Li, Fangcai
[1
]
Chen, Qixin
[1
]
机构:
[1] Zhejiang Univ, Affiliated Hosp 2, Sch Med, Dept Orthoped Surg, 88 Jiefang Rd, Hangzhou 310009, Peoples R China
[2] Zhejiang Univ, Dept Basic Med Sci, Sch Med, Hangzhou, Peoples R China
[3] Zhejiang Univ, Sir Run Run Shaw Hosp, Dept Orthopaed, Sch Med, Hangzhou, Peoples R China
基金:
中国国家自然科学基金;
关键词:
duraplasty after decompression;
inflammasome;
macrophage;
PHBV;
PLA;
Col membranes;
polarization;
spinal cord injury;
EARLY SURGICAL DECOMPRESSION;
DURAL SUBSTITUTE;
NANOFIBROUS SCAFFOLDS;
NEUROTROPHIC FACTORS;
LOCOMOTOR FUNCTION;
REPAIR;
MODEL;
FABRICATION;
PRESSURE;
EFFICACY;
D O I:
10.1096/fj.202000190RR
中图分类号:
Q5 [生物化学];
Q7 [分子生物学];
学科分类号:
071010 ;
081704 ;
摘要:
Duraplasty after decompression decreases the lesion size and scar formation, promoting better functional recovery, but the underlying mechanism has not been clarified. Here, we fabricated a series of poly(hydroxybutyrate-co-hydroxyvalerate)/polylactic acid/collagen (PHBV/PLA/Col) membranes and cultured them with VSC4.1 motor neurons. The material characteristics and in vitro biological characteristics were evaluated. In the subcutaneous implantation test, PHBV/PLA/COl scaffolds supported the cellular infiltration, microvasculature formation, and decreased CD86-positive macrophage aggregation. Following contusion spinal cord injury at T10 in Sprague-Dawley rats, durotomy was performed with allograft dura mater or PHBV/PLA or PHBV/PLA/Col membranes. At 3 days post-injury, Western blot assay showed decreased the expression of the NLRP3, ASC, cleaved-caspase-1, IL-1 beta, TNF-alpha, and CD86 expression but increased the expression of CD206. Immunofluorescence demonstrated that duraplasty with PHBV/PLA/Col membranes reduced the infiltration of CD86-positive macrophages in the lesion site, decreased the glial fibrillary acidic protein expression, and increased the expression of NF-200. Moreover, duraplasty with PHBV/PLA/Col membranes improved locomotor functional recovery at 8 weeks post-injury. Thus, duraplasty with PHBV/PLA/Col membranes decreased the glial scar formation and promoted axon growth by inhibiting inflammasome activation and modulating macrophage polarization in acute spinal cord injury.
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页码:12147 / 12162
页数:16
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