[关键词]
[摘要]
目的 研究芦荟大黄素对正常的和细菌脂多糖(LPS)刺激的大鼠腹腔巨噬细胞(PMφ)释放肿瘤坏死因子-α(TNF-α)和细胞内自由2+浓度([Ca2+]i)的影响。方法 应用MTT法检测TNF-α量和细胞钙离子成像系统检测单细胞内[Ca2+]i的动态变化。结果 芦荟大黄素可剂量依赖性活化正常PMφ释放TNF-α,同时诱发正常PMφ[Ca2+]i呈波动式变化,[Ca2+]i升高来源于胞外钙内流和胞内钙池释放钙。芦荟大黄素对LPS刺激PMφ升高[Ca2+]i和释放TNF-α的影响有较复杂的剂量依赖性特征,即芦荟大黄素低浓度时对[Ca2+]i升高有明确的抑制作用;其对TNF-α释放的抑制呈随浓度增高而减弱的趋势。大黄酸可增强芦荟大黄素对LPS升高[Ca2+]i的抑制作用。结论 芦荟大黄素对PMφ[Ca2+]i和释放TNF-α表现出双向调节作用,其对[Ca2+]i动力学的调制与其调节PMφ释放TNF-α间有明确的对应性。
[Key word]
[Abstract]
Objective To investigate the effects of aloe-emodin on free calcium concentration ([Ca2+]i) dynamics and tumor necrosis factor (TNF-α) production in normal and lipopolysaccharide (LPS)-stimulated peritoneal macrophages (PMφ) of rats. Methods To assay TNF-α and to detect cytosolic [Ca2+]i in single cell by MTT and image analysis system. Results Aloe-emodin increased TNF-α production by activating of normal PMφ in a dose-dependent manner. Furthermore, aloe-emodin caused [Ca2+]i oscillation in normal PMφ, the medicine induced [Ca2+]i increase, including calcium influx from extracellular medium and calcium release from intracellular calclum store. Aloe-emodin showed complex effects in a dose-dependent manner on LPS-stimulated PMφ. At low concentration, aloe-emodin could attenuate the transient increase in [Ca2+]i induced by LPS. The inhibition of aloe-emodin on TNF-α production induced by LPS decreased with the concentration increasing. Rhein could enhance the inhibition of aloe-emodin on increase in [Ca2+]i induced by LPS. Conclusion Aloe-emodin has bidirectional characteristics of regulation on TNF-α production and [Ca2+]i in PMφ. And the regulation of aloe-emodin on [Ca2+]i obviously corresponds to the regulation on TNF-α prodiction in PMφ.
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[基金项目]
天津市“九五”重点攻关项目《MODS发病机理及中西医结合治疗的深入研究》资助(983113411)