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透骨消痛胶囊调控Nav1.7减轻膝骨关节炎小鼠软骨细胞退变
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作者 付长龙 林艳铭 +4 位作者 兰书洁 陈悦 李超 陆诗雨 林晴 《南方医科大学学报》 CAS CSCD 北大核心 2024年第11期2074-2081,共8页
目的从Nav1.7调控软骨细胞外基质稳态角度,研究透骨消痛胶囊对减轻膝骨关节炎(KOA)软骨细胞退变的作用机制。方法选择40只2月龄C57BL/6小鼠,通过随机数字表法将其分为空白组(n=10)和造模组(n=30)。造模组小鼠通过Hulth法手术建立KOA模型... 目的从Nav1.7调控软骨细胞外基质稳态角度,研究透骨消痛胶囊对减轻膝骨关节炎(KOA)软骨细胞退变的作用机制。方法选择40只2月龄C57BL/6小鼠,通过随机数字表法将其分为空白组(n=10)和造模组(n=30)。造模组小鼠通过Hulth法手术建立KOA模型后,随机分为模型组(生理盐水灌胃)、透骨消痛胶囊组(368 mg/kg剂量灌胃)、阳性药物组(10 mg/kg双氯芬酸钠灌胃),10只/组;空白组为生理盐水灌胃,干预6次/周,共4周。干预后5%异氟醚麻醉处死,获得膝关节软骨组织。形态学染色观察软骨组织结构变化,实时荧光定量PCR检测Nav1.7 mRNA水平,Western blotting分析Nav1.7、MMP-3、ADAMTS-5、COX-2蛋白表达变化。荧光原位杂交检测软骨细胞中Nav1.7的表达量。此外,利用慢病毒载体敲减Nav1.7(sh-Nav1.7)转染软骨细胞,实时荧光定量PCR分析转染后sh-Nav1.7在软骨细胞中mRNA水平变化。Western blotting分析在sh-Nav1.7条件下,透骨消痛胶囊对KOA软骨细胞MMP-3、MMP-13、ADAMTS-4、ADAMTS-5、COX-2蛋白的调控。结果形态学结果显示,和模型组对比,透骨消痛胶囊组和阳性药物组软骨层结构更完整,关节结构破坏程度减轻。透骨消痛胶囊组和阳性药物组的Nav1.7蛋白与mRNA水平降低(P<0.05),MMP-3、ADAMTS-5、COX-2蛋白表达减少(P<0.05)。荧光原位杂交结果显示,透骨消痛胶囊能降低IL-1β诱导的Nav1.7的荧光强度。在Nav1.7敲减实验中,与IL-1β组相比,IL-1β+sh-Nav1.7组中Nav1.7水平下降(P<0.05);与IL-1β+TGXTC组相比,IL-1β+sh-Nav1.7+TGXTC组中Nav1.7水平下降(P<0.05)。Western blotting结果表明,IL-1β组软骨细胞中升高的MMP-3、MMP-13、ADAMTS-4、ADAMTS-5、COX-2蛋白被透骨消痛胶囊干预后显著抑制(P<0.05),但在Nav1.7敲低后,透骨消痛胶囊对这些蛋白的调控作用减弱(P<0.05)。结论透骨消痛胶囊通过调控Nav1.7减轻KOA软骨细胞外基质代谢紊乱,从而发挥减轻软骨细胞退变的作用。 展开更多
关键词 透骨消痛胶囊 Nav1.7 软骨退变 膝骨关节炎
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Functional biomaterials for modulating the dysfunctional pathological microenvironment of spinal cord injury 被引量:1
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作者 Dezun Ma Changlong Fu +5 位作者 Fenglu Li Renjie Ruan yanming lin Xihai Li Min Li Jin Zhang 《Bioactive Materials》 SCIE CSCD 2024年第9期521-543,共23页
Spinal cord injury(SCI)often results in irreversible loss of sensory and motor functions,and most SCIs are incurable with current medical practice.One of the hardest challenges in treating SCI is the development of a ... Spinal cord injury(SCI)often results in irreversible loss of sensory and motor functions,and most SCIs are incurable with current medical practice.One of the hardest challenges in treating SCI is the development of a dysfunctional pathological microenvironment,which mainly comprises excessive inflammation,deposition of inhibitory molecules,neurotrophic factor deprivation,glial scar formation,and imbalance of vascular function.To overcome this challenge,implantation of functional biomaterials at the injury site has been regarded as a potential treatment for modulating the dysfunctional microenvironment to support axon regeneration,remyelination at injury site,and functional recovery after SCI.This review summarizes characteristics of dysfunctional pathological microenvironment and recent advances in biomaterials as well as the technologies used to modulate inflammatory microenvironment,regulate inhibitory microenvironment,and reshape revascularization microenvironment.Moreover,technological limitations,challenges,and future prospects of functional biomaterials to promote efficient repair of SCI are also discussed.This review will aid further understanding and development of functional biomaterials to regulate pathological SCI microenvironment. 展开更多
关键词 Spinal cord injury Dysfunctional pathological microenvironment Functional biomaterials Axon regeneration Functional recovery
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