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国家自然科学基金(30570865)

作品数:4 被引量:16H指数:2
相关作者:李晓陈楠周同毛朝明许春娣更多>>
相关机构:上海交通大学医学院附属瑞金医院上海交通大学上海血液学研究所更多>>
发文基金:国家自然科学基金上海市基础研究重大(重点)项目上海市自然科学基金更多>>
相关领域:医药卫生更多>>

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Valsartan Inhibited the Accumulation of Dendritic Cells in Rat Fibrotic Renal Tissue被引量:5
2006年
To observe the accumulation of dendritic cells (DCs) in rat remnant kidney and its contribution to tubulointerstitial fibrosis, under influence of valsartan on DCs, a rat remnant kidney model was established by subtotal nephrectomy. Four experimental groups were included: normal, sham, model (SNx) and the group treated with Valsartan (SNxV). Rats were killed at week 1, 4 and 12, respectively. CD1a^+CD80^+ DCs were assayed by double immunostaining method and the images were analyzed with Axioplan 2 microscopy. The expressions of P-selectin, TGF-β1, α-SMA, collagen Ⅲ and fibronectin were analyzed by immunohistochemistry or semi- quantitative RT-PCR, and the level of tubulointerstitial firosis (TIF) was scored. CD1a^+CD80^+ DCs were gradually increased among renal tubules, interstitium and vessels, especially in interstitium, and the number of DCs in model group at week 12 was much more than that in model groups at week 1 or 4. The expressions of P-selectin, TGF-β1, α-SMA, collagen Ⅲ and fibronectin in tubulointerstitial areas and the degree of TIF were increased substantially in model group at week 12. The accumulation of DCs in interstitium was well associated with the loss of renal function and the progression of tubulointerstitial fbrosis. Valsartan treatment inhibited the local accumulation of DCs and attenuated renal tubulointerstitial damage. The local DCs accumulation was related to tubulointerstitial fibrosis and renal dysfunction following renal ablation. Blockade to angiotensin II might be a potent way to attenuate renal immuno-inflammatory injury. Cellular & Molecular Immunology. 2006;3(3):213-220.
Kaiyin WuTong ZhouGuizhi SunWeiming WangYumei ZhangYanyun ZhangLi HaoNan Chen
关键词:NEPHRECTOMYVALSARTAN
DC-SIGN and Immunoregulation被引量:12
2006年
Dendritic cells (DCs) are known to be the most powerful professional antigen-presenting cells so far. It could activate primary immune response, and also downregulate immune response. DCs have a unique character of immunoregulation. DC-SIGN, a molecule designated as CD209, is one member of the C-type lectin superfamily. It is not only a pattern recognition receptor but implicated in immunoregulation of DCs. DC-SIGN has become hotspot of recent studies because of its important role in mediating DC adhesion, migration, inflammation, activating primary T cell, triggering immune response and participating in immune escape of pathogens and tumors. These studies on DC-SIGN involved in primary and secondary immune response and relevant mechanism will certainly provide us with a new method in treating and preventing certain diseases.
Tong ZhouYongxi ChenLi HaoYanyun Zhang
关键词:DCDC-SIGNIMMUNOREGULATION
P选择素在肾病综合征并发深静脉血栓中的作用及犬血栓模型磁共振分子成像观察
2008年
目的观察P选择素在肾病综合征(NS)并发深静脉血栓形成(DVT)中作用,探讨P选择素靶向对比剂及分子磁共振成像(MRI)在DVT犬模型早期诊断应用的可行性。方法(1)选择我院2005年至2006年间住院NS患者41例,根据核素深静脉造影检查有无伴发DVT,再分为DVT组和无DVT组,检测患者血中P选择素含量。(2)选择健康成年毕格犬,建立DVT模型,并按造模即刻、1h、3h采血并取静脉损伤节段,行血管组织和血中P选择素含量检测。(3)利用研制的抗P选择素单抗,制成P选择素靶向对比剂,结合体外犬静脉损伤节段血管MRI,进行犬活体内观察。结果(1)NS患者血P选择素水平较健康组显著增高(P〈O.01),DVT组又较无伴DVT组明显增高(P〈0.01)。(2)模型犬血P选择素水平较对照犬显著增高(P〈0.05),且于受损血管内膜及血栓形成部位明显表达。(3)制备的MRI对比剂,体外可明显增强犬离体受损血管与血栓部位显像信号。体内于犬静脉损伤局部注射对比剂30min,MRI即显示高于周围肌肉显影的血管信号;1h可见附壁血栓增强信号;至3h随血栓形成增大而持续强化,实验组对比度噪声比(CNR)值与对照组比较,差异有统计学意义(11.51±2.32比2.71±O.86,P〈0.01),且显示了与P选择素表达一致的信号强化效果。另从犬损伤部位远心端注射对比剂30rain至1h,也显示了上述成像效果;2h至4h血栓信号由明显上升渐见趋缓,延迟24h信号强度减弱,实验组CNR值与对照组间差异也有统计学意义(10.40±2.15比1.93±0.57,P〈0.01)。此外,该对比剂对实验犬的生命体征及心、肺、肝、肾等脏器均无明显影响。结论P选择素参与NS合并DVT。利用P选择素单抗MRI对比剂,可在活体内早期定位显像及反映血栓形成状态,为DVT早期诊断提供了一种可行方法。
周同李晓赵亚鹏金佩佩王学锋钟高仁汪登斌张明钧陈楠王鸿利
关键词:肾病综合征静脉血栓形成磁共振成像P选择素
树突状细胞DC-SIGN在免疫介导实验性肾炎肾小管间质损伤中的作用及抗P选择素功能域单抗的干预调节被引量:1
2010年
目的 探讨树突状细胞(DC)表面特异的胞间黏附分子3捕获非整合素(DC-SIGN)在免疫介导肾毒血清件肾炎(NTN)肾小管间质损伤中的作用,以及抗P选择素功能域单抗(PsL-EGFmAb)的干预调节.方法 WKY大鼠随机分为正常对照组、模型组及PsL-EGFmAb干预组.模型组注射预制的兔抗大鼠肾毒血清1 nd/kg;PsL-EGFmAb组在注射肾毒血清同时及注射后2 h,注入PsL-EGFmAb 2 mg/kg;正常对照组则注射等量生理盐水.随后于实验第4、7、14天,分别观察大鼠肾功能及肾组织病理变化,并采用免疫荧光法检测肾组织DC-SIGN+DC分布;实时定量PCR检测P选择素、T细胞表达和分泌因子(RANTES)、肿瘤坏死因子α(TNF-α)、白细胞介素(IL)-10、干扰素(IFN)-γ、IL-4的mRNA表达;流式细胞仪检测肾脏分离DC表面主要组织相容性复合体Ⅱ(MHC Ⅱ)、DC-SIGN、CD80表达;细胞迁移试验及混合淋巴细胞反应(MLR)检测DC迁移与刺激T细胞的能力;ELISA法测定MLR上清中IFN-γ、IL-4含量.结果 NTH大鼠第4天起,未成熟DC-SIGN+DC即以肾间质为主浸润并于14 d成熟,且迁移及刺激T细胞增殖能力增强,其肾内分布与新月体形成、肾小管间质损伤程度及肾功能改变呈正相关.此外,大鼠第4天起肾内趋化因子及促炎因子RANTES、TNF-α mRNA表达持续上调,而抗炎因子IL-10 mRNA于第4天明显增强随后呈下调趋势;至14 d时IFN-γ/IL-4 mRNA比值增高,与DC成熟状况呈正相关.经PsL-EGFmAb干预,伴随Dc表面DC-SIGN及相应共刺激分子CD80表达下降,DC成熟、迁移及刺激T细胞增殖能力受抑,肾内促炎因子下降而抗炎因子上调,Th1/Th2偏移受到抑制.同时大鼠肾内新月体形成减少,肾小管间质损伤程度减轻,且肾功能改善.结论 DC-SIGN介导了DC肾间质浸润,并可能是局部免疫反应失衡以及肾小管间质病变的重要调控因素.PsL-EGFmAb在抑制DC迁移的同时可通过靶向DC-SIGN调抑DC成熟及功�
蔡敏超邹杰周同李晓陈静毛朝明张雁云陈楠许春娣
关键词:P选择素肾小管间质损伤DC-SIGN
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