摘要
目的 :探讨磷脂酸在肾小球巨噬细胞表达几种炎症介导因子中的作用。方法 :采用加速型抗肾小球基底膜肾炎模型 ,分离肾小球巨噬细胞 ,以其腹腔巨噬细胞和正常鼠腹腔巨噬细胞做对照 ,用重组人白细胞介素1β(rhIL - 1β)刺激 ,磷脂酸抑制剂 (LSF)和磷脂酸 (PA)进行阻断及逆转实验。通过免疫细胞化学 ,Northern杂交和RT -PCR等方法 ,从蛋白和基因水平检测巨噬细胞表达ICAM - 1、MCP - 1和TGF - β1的情况。结果 :①炎症肾小球巨噬细胞在rhIL - 1β刺激下比腹腔巨噬细胞和未刺激的巨噬细胞产生更多的ICAM - 1、MCP - 1、TGF - β1,其基因表达与蛋白产物相似 ;而且能被LSF抑制。②RT -PCR结果显示加入外源PA可逆转LSF对炎症肾小球巨噬细胞的上述炎症介导因子基因表达的阻断作用。结论 :肾小球炎症的巨噬细胞产生TGF - β1可能对疾病的慢性进展起重要作用 ;抑制PA形成是阻断巨噬细胞介导炎症效应的新靶位 ,LSF有可能成为治疗肾小球肾炎的新药。
AIM: To investigates the role of phosphatidic acid (PA) in the expression of several inflammatory mediators produced by glomerural macrophages (GMΦ). METHODS: The study was performed on a rat model of accelerated anti-glomerural basement membrane (anti-GBM) glomerulonephritis (GN). GN-GMΦ were isolated and identified. Peritoneal MΦ (P-MΦ) of both normal and GN rats were used as controls. Block and reverse test were investigated with rhIL-1β stimulated, lisofylline (LSF) and phosphatidic acid (PA). Macrophage expression of ICAM-1 and TGF-β 1 were assessed at the level of protein and gene by immunocytochemistry, northern blot and RT-PCR. RESULTS: (1) After stimulated with rhIL-1β, GN-GMΦ produced much more ICAM-1, MCP-1 and TGF-β 1 than P-MΦ, and it's gene expression was similar as protein product. (2) mRNA expression of these factors was up-regulated again after the GN-GMΦ were pretreated with LSF then PA was added. CONCLUSIONS: Since GN-GMФ plays an important role for PA in the mediation of glomerular injury, inhibiting of PA production is the keypoint of blocking MФ mediated inflammatory effects. LSF may be an effective medicine in therapy for acute inflammatory forms of GN.
出处
《中国病理生理杂志》
CAS
CSCD
北大核心
2003年第6期721-725,共5页
Chinese Journal of Pathophysiology
基金
国家自然科学基金资助项目 (No .390 70 389)
卫生部"九五"攻关基金资助项目 (96 92 0 0 6 0 5 14 )
关键词
肾炎
巨噬细胞
炎症
转化生长因子β
磷脂酸类
Nephritis
Macrophages
Inflammation
Transforming growth factor beta
Phosphatidic acids
