摘要
以正常腹腔巨噬细胞(PMΦ)和脂多糖(Lipopolysacharide,LPS)刺激的PMΦ为对象,用MTT法和激光共焦扫描显微术检测肿瘤坏死因子α(TNFα)释放量和单细胞[Ca2+]i的动态变化,研究了大黄酸(Rhein)的作用特征和机理.结果显示,大黄酸对正常PMΦ释放TNFα没有明确的影响,但对LPS刺激的PMΦ释放TNFα有显著的抑制作用,其抑制作用随浓度增加而增强,10-4mol/L大黄酸抑制了10μg/mL LPS效应的72％.值得注意的是,大黄酸不但抑制了LPS引发的PMΦ[Ca2+]i的升高,而且使LPS引发的[Ca2+]i由宽平台峰状转变为振荡动力学模式,胞外介质无钙时又转变为更低幅值的峰.以上结果表明,大黄酸降低LPS引发的PMΦ的[Ca2+]i升高是其抑制TNFα释放的信号传导通路的重要环节,并提示大黄酸在降低胞内钙释放和胞外钙内流的同时又对其动力学进行了类周期性的调制.
Using confocal laser scanning microscopy and MTT assay, the effects of Rhein on single cell [Ca2+ ]i dynamics and TNFα production in normal and LPS-stimulated rat peritoneal macrophages (PMΦ)?were investigated. Rhein had not a disinct effect on TNFα production in normal PMΦ, but could obviously inhibit TNFα release in LPS-stimulated PMΦ in dose-dependent manner. 10-4 mol/L Rhein could inhibit the effect of LPS by 72%. Noticeably, Rhein not only lowered the rising of [Ca2+]i in LPS-stimulated PMΦ, but also altered the dynamical mode of [Ca2+]i, which means that Rhein could transform the 'plateau-shaped' peak of [Ca2+]i into the oscillating mode. In the case of extracellular Ca2+-free, Rhein further transformed the [Ca2+]i dynamics into a single peak of lower amplitude. These results indicate that Rhein reducing the increase in [Ca2+]i is the key of signal transduction pathway that Rhein inhibited the TNFα production in LPS-stimulated PMΦ. It further suggests that inhibition and quasi-periodic modulation on influx of extracellular calcium as well as on intracellular calcium release in involve in the regulative mechanism of Rhein.
出处
《南开大学学报（自然科学版）》
CAS
CSCD
北大核心
2003年第3期111-115,共5页
Acta Scientiarum Naturalium Universitatis Nankaiensis
基金
天津市九.五重点科技攻关基金资助项目(983113411)
