Stenstad T, Husby G
Department of Rheumatology, University of Tromsø, Norway.
J Rheumatol. 1996 Jan;23(1):93-100.
Brefeldin A, an antibiotic with effects on certain intracellular compartments, was tested on murine secondary AA amyloidosis. Effects on splenic proteoglycan metabolism were analyzed along with plasma serum amyloid A (SAA) levels.
Brefeldin A was administered daily to mice undergoing inflammatory stimulation with complete Freund's adjuvant to induce reactive AA amyloidosis. AA amyloid deposition was assessed using histochemistry, immunohistochemistry, and electron microscopy. Sodium dodecyl sulfate polyacrylamide gel electrophoresis and Western blotting were used to detect SAA in acute phase serum. Relative (semiquantitative) measurements of total SAA levels were obtained by densitometry of stained gels. Splenic proteoglycan metabolism was analyzed in treated animals and compared to untreated individuals by in vivo 35S administration during amyloid fibrillogenesis.
Based on (immuno)histochemistry and electron microscopy, animals undergoing drug treatment did not develop splenic amyloidosis, whereas the control animals exhibited massive amyloid fibril deposits in the spleen (p < 0.001). SAA was detected at roughly equal quantities in serum from both groups. No significant qualitative or quantitative difference in proteoglycan synthesis was found.
Brefeldin A seems to exert an inhibitory action on murine AA amyloidosis. It appears that the effect does not depend on the lack of fibril protein precursor nor altered proteoglycan synthesis.
布雷菲德菌素A是一种对某些细胞内区室有作用的抗生素，对小鼠继发性AA淀粉样变性进行了测试。分析了其对脾脏蛋白聚糖代谢的影响以及血浆血清淀粉样蛋白A（SAA）水平。
对用完全弗氏佐剂进行炎症刺激以诱导反应性AA淀粉样变性的小鼠每日给予布雷菲德菌素A。使用组织化学、免疫组织化学和电子显微镜评估AA淀粉样蛋白沉积。用十二烷基硫酸钠聚丙烯酰胺凝胶电泳和蛋白质印迹法检测急性期血清中的SAA。通过对染色凝胶进行光密度测定获得总SAA水平的相对（半定量）测量值。在淀粉样纤维形成过程中，通过体内给予35S对治疗动物的脾脏蛋白聚糖代谢进行分析，并与未治疗的个体进行比较。
基于（免疫）组织化学和电子显微镜检查，接受药物治疗的动物未发生脾脏淀粉样变性，而对照动物在脾脏中表现出大量淀粉样纤维沉积物（p < 0.001）。两组血清中检测到的SAA量大致相等。在蛋白聚糖合成方面未发现明显的定性或定量差异。
布雷菲德菌素A似乎对小鼠AA淀粉样变性具有抑制作用。其作用似乎不取决于纤维蛋白前体的缺乏或蛋白聚糖合成的改变。
