氯化钆对大鼠腹腔巨噬细胞表达CD68的影响  

Effects of gadolinium chloride on CD68 expression of rat peritoneal macrophages

作　　者：黄学桂[1,2] 王法财[1,2] 王海萍[1] 路锦涛[2] 沈玉君[1] 沈玉先[1] 

机构地区：[1]安徽医科大学教育部"重要遗传疾病基因资源利用"重点实验室(省部共建),合肥230032 [2]安徽医科大学临床药理研究所,合肥230032

出　　处：《安徽医科大学学报》2009年第1期68-71,75,共5页Acta Universitatis Medicinalis Anhui

基　　金：国家自然科学基金(编号:30572219;30772557;30870881);安徽省科技攻关项目(编号:07010300191)

摘　　要：目的观察氯化钆(GdCl3)对大鼠腹腔巨噬细胞(PMΦ)表达CD68是否有抑制作用。方法取正常大鼠PMΦ体外培养,用不同浓度的GdCl3处理PMΦ;采用弗氏完全佐剂(FCA)诱导大鼠佐剂性关节炎(AA)模型并尾静脉注射GdCl3。采用免疫荧光双标、Western blot法检测PMΦ活化标记物CD68的表达情况。结果在一定的浓度范围内,GdCl3可抑制体外培养的正常大鼠PMΦ中CD68的表达,以5×10-6mol/L浓度抑制效果最明显。大剂量的GdCl3对细胞有明显的毒性作用,表现为细胞的形态和核发生改变,并可诱导内质网(ER)应激相关蛋白ARMET的表达。对于AA大鼠活化的PMΦ,体内注射GdCl3(10mg/kg)可使部分CD68阳性的PMΦ转阴,同时促进这些阴性细胞的分化;GdCl3并可诱导部分活化的PMΦ凋亡。结论GdCl3可以抑制大鼠PMΦ中CD68的表达及诱导活化的PMΦ凋亡,这可能是GdCl3抑制PMΦ活化的机制之一。Objective To investigate whether gadolinium chloride inhibits the expression of CD68 in rat peritoneal macrophages （PMΦs）. Methods PMΦs were isolated from normal SD rats and treated with different concentrations of gadolinium chloride （ GdCl3 ）. Rat adjuvant arthritis （AA） was induced by Freund＇s complete adjuvant （FCA）. PMΦs were harvested after injection of GdCl3 through tail vein. Double immunofluoreseence labeling and western blotting were used to determine the expression of CD68. The nuclus were stained by DAPI. TUNEL staining was used to determine the apoptotic PMΦs. Results GdCl3 dose-dependently inhibited the expression of CD68 in PMΦs from normal rats. The optimal concentration was 5 × 10^-6 mol/L. The higher concentrations of GdCl3 were toxic to PMΦs, including the changes in cellular morphologies and nuclus. Furthermore, it up-regulated the expression of ARMET, a secreting protein inducible to ER stress at the higher concentrations. GdCl3 also turn some of the CD68- positive PMΦs of AA rats to negative ones and promoted these negative PMΦs differentiation at the dose of 10 mg/ kg. Meanwhile, GdCl3 induced some of the activated PMΦs apoptosis. Conclusion GdCl3 inhibits the expression of CD68 both in normal and activated PMΦs and induces PMdPs apoptosis, which probably is one of the mechanisms that contribute to the inhibition of PMΦ activation.

关 键 词：氯化钆/药理学 关节炎 佐剂性 巨噬细胞 腹膜 

分 类 号：R657.5[医药卫生—外科学]