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作 者:赵腾斐[1] 张倩[1] 张雯[1] 吴皓[1,2,3] 郁红礼[1,2,3] 王慧珠[1,4]
机构地区:[1]南京中医药大学药学院,江苏南京210046 [2]江苏省中药炮制重点实验室,江苏南京210046 [3]国家教育部中药炮制规范化及标准化工程研究中心,江苏南京210046 [4]南京中医药大学国家科技部规范化中药药理实验室,江苏南京210046
出 处:《中国中药杂志》2013年第7期1041-1045,共5页China Journal of Chinese Materia Medica
基 金:国家自然科学基金项目(30772785;30973939);国家"重大新药创制"科技重大专项(2009ZX09308-004)
摘 要:目的:研究半夏毒针晶刺激性毒性产生的机制。方法:采用小鼠腹腔巨噬细胞体外培养模型,以培养上清液中TNF-α,IL-1β和IL-6为指标,研究半夏毒针晶致炎的量-毒,时-毒曲线;采用扫描电镜法观察经半夏毒针晶刺激后巨噬细胞表面形态学的改变;使用巨噬细胞-中性粒细胞共培养迁移模型,考察半夏毒针晶刺激巨噬细胞对中性粒细胞迁移的影响。结果:半夏毒针晶刺激巨噬细胞,可引起TNF-α,IL-1β和IL-6含量显著升高,且具有剂量和时间依赖性;扫描电镜显示,半夏毒针晶可被巨噬细胞吞噬,细胞膜表面皱褶明显,伪足数量增多,细胞膜完整性下降,并能显著诱导中性粒细胞迁移。结论:巨噬细胞在毒针晶的致炎过程中起关键的介导作用。半夏毒针晶的毒性机制是毒针晶刺入组织,激活组织中的驻留巨噬细胞,引起吞噬、促炎细胞因子释放、中性粒细胞大量迁移,最终导致强烈的急性炎症反应。Objective: To study the toxic mechanism of toxic raphides from Pinellia ternata. Method: Mouse peritoneal macrophage in vitro culture model was adopted to study dose-dependent and time-dependent curves of toxic raphides, with TNF-α, IL-β and IL-6 in supernatant as indexes. Scanning electron microscopy was used to observe the changes in surface morphology of raphidestreated macrophages. Macrophages-neutrophils co-cuhured the transport model to study the effect of toxic raphides' stimulation of macrophages on neutrophils migration. Result: Toxic raphides' stimulation of macrophages could cause the increase in the levels of TNF- α, IL-β and IL-6 released, and showed dose dependence and time dependence. Scanning electron microscopy showed that toxic raphides were swallowed by macrophages, with notable cell membrane creases, increase in the number of pseudopods and decrease in in- tegrity of cell membranes, and could significantly induce migration of neutrophils. Conclusion: The inflammatory process induced by toxic raphides is mainly mediated by macrophages. The toxic mechanism of toxic raphides from P. ternata is that toxic raphides penetrate into tissues to activate resident macrophages, release phagocytic and inflammatory eytokines, and cause migration of neutrophils, which finally results in acute inflammatory response.
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