上海交通大学学报（医学版）2025，Vol.45Issue(9)：1161-1170,10.DOI:10.3969/j.issn.1674-8115.2025.09.008
负载白细胞介素-4的水凝胶微球调控卒中后免疫微环境对神经功能修复的影响
Effects of hydrogel microspheres loaded with interleukin-4 on neural functional recovery by modulating the immune microenvironment after stroke
摘要
Abstract
Objective·To explore the effects of hydrogel microsphere(MP)loaded with the immunoregulatory factor interleukin-4(IL-4)on the regeneration and repair after stroke injury.Methods·IL-4-loaded nanoparticles were prepared using an emulsification method and subsequently incorporated into polyvinyl alcohol(PVA)hydrogel microspheres via an airflow technique to obtain IL-4-loaded PVA hydrogel microspheres(MP@IL-4).The morphology of MP@IL-4 was characterized by optical microscopy.BV2 microglia were cultured in vitro and treated with MP@IL-4.Cell viability and survival were detected by the CCK-8 assay and live/dead cell staining,respectively.Subsequently,BV2 microglia were further treated with lipopolysaccharide(LPS),and the expression levels of the pro-inflammatory marker inducible nitric oxide synthase(iNOS)and the anti-inflammatory marker arginase 1(Arg-1)were detected by immunofluorescence staining.Meanwhile,a mouse stroke model was constructed using the middle cerebral artery occlusion method,and the mice were randomly divided into the sham operation group(Sham group),the ischemic stroke(IS)group and the microsphere treatment group(IS-MP@IL-4 group).The neurobehavioral functions of mice in the three groups were detected by the modified Neurological Severity Score,elevated body swing test,and hanging wire test.The brain atrophy volume was detected by cresyl violet staining.Immunofluorescence staining was used to assess the expression levels of the pro-inflammatory factor CD86 and the anti-inflammatory factor CD206 in microglia.Results·Optical microscopy confirmed the successful fabrication of MP@IL-4 with a particle size of 200 μm,which did not affect the cell viability and survival of BV2 microglia.Both in vitro and in vivo experiments demonstrated that MP@IL-4 downregulated the expression of pro-inflammatory markers and upregulated the expression of anti-inflammatory markers in microglia.Moreover,compared with the IS group,the neurobehavioral function of mice in the IS-MP@IL-4 group was significantly improved(P<0.05),and the brain atrophy volume was reduced(P<0.001).Conclusion·MP@IL-4 can exert a therapeutic effect on post-stroke neurofunctional injury by improving the immune microenvironment.关键词
水凝胶微球/药物递送/缺血性卒中/抑炎作用/神经修复Key words
hydrogel microsphere/drug delivery/ischemic stroke(IS)/anti-inflammatory effect/neural repair分类
医药卫生引用本文复制引用
徐彤彤,阮慧瞳..负载白细胞介素-4的水凝胶微球调控卒中后免疫微环境对神经功能修复的影响[J].上海交通大学学报（医学版）,2025,45(9):1161-1170,10.基金项目
国家自然科学基金(82372120) （82372120）
上海交通大学医学院"双百人"项目(2024-0701). National Natural Science Foundation of China(82372120) （2024-0701）
"Two-hundred Talents"Program of Shanghai Jiao Tong University School of Medicine(2024-0701). （2024-0701）
