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国家自然科学基金(30901431)

作品数:4 被引量:14H指数:3
相关作者:施晓雷檀家俊丁义涛肖江强张玲更多>>
相关机构:南京大学医学院附属鼓楼医院东南大学更多>>
发文基金:国家自然科学基金更多>>
相关领域:医药卫生化学工程更多>>

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Fabrication IL-1Ra loaded galactosylated chitosan nanoparticles for liver targeting
2012年
Galactosylated chitosan (GC) is synthesized and used to prepare IL-1Ra loaded GC nanoparticles by an electrospraying technique. Polyethylene oxide (PEO) is mixed with GC to enhance the electrospraying ability. The effect of the spraying solution properties on particle formation is investigated. The IL-1Ra loaded nanoparticles with an average diameter of 530 nm and a regularly spherical shape are observed by the scanning electron microscopy (SEM). The amount of the IL-1Ra is measured by the enzyme-linked immunosorbent assay (ELISA) kit. The loading capacity of the nanoparticle is (1.52± 0.04)% (n = 3) and the encapsulation efficiency reaches (90. 36 ± 3.46) % (n = 3). For the evaluation of GC nanoparticles' hepatocytes targeting efficacy, hepatocytes and mesenchymal stem cells (MSCs) are incubated with FITC-labeled GC nanoparticles for 24 h as the experimental and control groups. Results of the fluorescence microscope show that the fluorescence signals observed in hepatocytes are significantly higher than in the MSCs, indicating that the developed GC nanoparticles have an obvious liver targeting property.
张玲檀家俊施晓雷徐师许茜
关键词:NANOPARTICLEELECTROSPRAYING
白介素1受体拮抗剂壳聚糖纳米颗粒联合骨髓间充质干细胞移植治疗急性肝衰竭的实验研究被引量:4
2013年
目的探讨炎症因子白细胞介素1受体拮抗剂(IL-1Ra)与骨髓间充质干细胞(MSCs)移植联合治疗肝功能衰竭的协同效应及其机制。方法采用静电喷射法制备IL-1Ra壳聚糖纳米颗粒,酶联免疫吸附法测定IL-1Ra纳米颗粒体外缓释作用,荧光显微镜和流式细胞术观察纳米颗粒肝细胞靶向性。将IL-1Ra纳米颗粒与MSCs联合治疗急性肝衰竭(ALF)幼猪,具体方法为:D-氨基半乳糖诱导建立猪ALF模型,34头中华实验小型猪随机分为5组,造模对照组经门静脉注射等渗盐水;IL-1Ra组经门静脉注射等渗盐水6h前耳背大静脉推注IL-1Ra;MSCs组经门静脉移植MSCs;IL-1Ra联合MSCs组和IL-1Ra纳米颗粒联合MSCs组先由耳背大静脉分别推注IL-1Ra或IL-1Ra纳米缓释颗粒,再经门静脉移植异体MSCs。移植后4周内定期检测肝功能、炎症因子变化和病理改变,并监测移植细胞体内存活、转化和分淤情况。组间数据比较用独立样本t检验。结果IL-1Ra纳米颗粒在磷酸盐缓冲液中呈现缓慢释放过程;绿色荧光显示乳糖酰基化的纳米颗粒能特异性地靶向到肝细胞。IL-1Ra纳米颗粒联合MSCs组具有显著炎症环境改善作用,与对照组相比,肿瘤坏死因子α在术后1周即明显下降,而IL-6水平在各时间点均明显降低;且IL—IRa纳米颗粒联合MSCs有促进肝功能恢复和肝脏细胞增殖的作用[术后第3周,每个200倍视野下的细胞数为(68.8±9.1)个,与对照组的(21.2±2.5)个相比,t=5.173,P〈0.01];免疫组织化学及荧光显微镜显示该组MSCs存活数量明显增多;Westernblot结果显示该组分泌肝细胞生长因子及血管内皮生长因子较其余各组明显增多。结论IL-1Ra乳糖酰基壳聚糖纳米颗粒具有良好的肝脏靶向和药物缓释作用,联合MSCs移植具有明显协同作用,通过改善炎症环境和分泌多种细胞因子显著改善D-氨基半乳糖诱导的ALF动�
肖江强施晓雷檀家俊张玲许茜丁义涛
关键词:间质干细胞移植壳聚糖白细胞介素1受体拮抗剂
白细胞介素1受体拮抗剂联合骨髓间充质干细胞移植治疗猪急性肝衰竭被引量:4
2012年
目的观察白细胞介素1受体拮抗剂(IL-1Ra)联合同种异体骨髓间充质干细胞(MSCs)移植对猪急性肝功能衰竭的协同治疗作用。方法采用D-氨基半乳糖(D-Gal)诱导建立猪急性肝功能衰竭模型。21只中华实验小型猪随机分为3组(n=7),对照组(A):诱导24h后,门静脉移植生理盐水40ml;单纯MSCs移植组(B):诱导24h后,门静脉移植8×10^7个MSCs;联合治疗组(C):诱导24h后,门静脉移植8×10^7个MSCs。分别在移植前6h、移植后1、3d猪耳背大静脉推注IL-1Ra共10mg。移植后4周内定期检测肝功能、病理改变和炎性因子变化并监测移植细胞体内存活转化情况。结果联合治疗组在促进肝功能恢复、改善炎症环境和减轻肝脏损伤方面较对照组和单纯MSCs移植组差异有统计学意义(P〈0.05);免疫组织化学显示联合治疗组肝细胞增殖率在1周后分别为67.70±9.47、71.80±9.45和40.04±4.60,显著高于对照组和单纯移植组,与对照组差异有统计学意义(P〈0.05);免疫组织化学和荧光染色法均可见联合治疗组干细胞植入数要高于单纯移植组。IL-1Ra在改善肝衰竭炎症内环境中发挥重要作用,通过对宿主炎症反应的有效控制可以显著提高移植细胞的植入率,促进肝细胞再生。结论IL-1Ra联合MSCs移植治疗具有协同作用,可以显著改善D-Gal诱导的猪急性肝衰竭的肝功能指标,促进肝组织再生。
施晓雷檀家俊肖江强任昊桢丁义涛
关键词:白细胞介素1受体拮抗剂骨髓间充质干细胞细胞移植急性肝衰竭
Effects of xenogeneic adipose-derived stem cell transplantation on acute-on-chronic liver failure被引量:7
2013年
BACKGROUND:Adipose-derived stem cells(ADSCs) are particularly attractive in future clinical applications of stem cell-based therapy for acute-on-chronic liver failure(ACLF) This study was undertaken to evaluate the therapeutic potential of ADSCs on ACLF.METHODS:ADSCs isolated from porcine fat tissue were expanded and labeled with BrdU.Rabbit models of ACLF were created by administration of D-Gal following CCl 4-induced cirrhosis.One day after administration of D-Gal,rabbits of the ACLF/ADSCs group(n=15) were received ADSCs transplantation,while those in the ACLF/saline group(n=15) were treated with the same volume of saline.Biochemical parameters and histomorphological scoring were evaluated;the distribution and characteristics of transplanted ADSCs as well as the pathology of the liver were examined.RESULTS:ADSCs transplantation improved the survival rate and the liver function of rabbits with ACLF.Biochemical parameters of the ACLF/ADSCs group were improved compared with those of the ACLF/saline group,and histomorphological scoring of the ACLF/ADSCs group was significantly lower than that of the ACLF/saline group.ADSCs were identified in the periportal region of the liver after cell transplantation.CONCLUSION:Xenogenic ADSCs have therapeutic efficacy in the ACLF rabbit model.
Wei ZhuXiao-Lei ShiJiang-Qiang XiaoGuang-Xiang GuYi-Tao DingZheng-Liang Ma
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