蛇床子素抑制LPS诱导的肠上皮细胞株Caco2的炎症反应  

Osthole attenuates LPS-induced inflammatory response in Caco2 cells

作　　者：孙武[1] 张欣欣[1] 周文博[1] 李皓[1] 

机构地区：[1]南京医科大学病理生理学系,江苏南京211166

出　　处：《南京医科大学学报（自然科学版）》2017年第7期814-817,共4页Journal of Nanjing Medical University(Natural Sciences)

基　　金：国家自然科学基金(81270944)

摘　　要：目的:探讨蛇床子素(osthole)对内毒素(lipopolysaccharide,LPS)诱导的肠上皮细胞Caco2中炎症因子表达的影响及机制。方法:培养Caco2细胞,用LPS诱导炎症反应。在LPS刺激前给予细胞不同浓度的蛇床子素处理,通过real-time PCR检测白介素(interleukin,IL)-1β、IL-6和肿瘤坏死因子(tumor necrosis factor,TNF)-α的表达情况。分别用PKA抑制剂H89和KT5720处理细胞,观察cAMP/PKA信号通路对蛇床子素效应的影响;用Western blot检测细胞中p38、Erk和JNK的磷酸化水平。结果:LPS刺激可以显著增加Caco2细胞中炎症因子IL-1β、IL-6和TNF-α的表达。蛇床子素预处理对LPS诱导的炎症反应有明显抑制作用,PKA抑制剂H89和KT5720不能逆转蛇床子素的抑制作用。LPS刺激后,Caco2细胞中p38、Erk和JNK的磷酸化水平明显增加,蛇床子素可部分抑制它们的磷酸化。结论:蛇床子素具有抑制肠上皮细胞株Caco2炎症反应的效应,该效应不依赖于cAMP/PKA,可能与抑制Erk、JNK和p38的磷酸化有关。Objective：To investigate the effect of osthole on lipopolysaccharide （LPS）-induced inflammatory response in Caco2 cells and the underlying mechanism. Methods：Caco2 cells were treated with various concentrations of osthole prior to LPS treatment. The mRNA levels of intedeukin （IL）-ll3,IL-6 and TNF-ct were detected by real-time PCR. Cells were treated with PKA inhibitors H89 or KT5720 prior to LPS at indicated doses to observe the effect of cAMP/PKA signaling pathway on osthole. The phosphoryla- tions of p38 ,Erk and JNK were detected by Western blot. Results：The expressions of inflammatory factors IL-li3,IL-6 and TNF-ct in Caco2 cells were significantly increased by LPS stimulation. Pretreatment of osthole significantly suppressed the up-regulation of in- flammatory cytokines induced by LPS. PKA inhibitors failed to reverse the inhibitory effect of osthole. LPS induced significant phos- phorylation of p38 ,Erk,and JNK in Caco2 cells,which were suppressed partly by osthole. Conclusion： Osthole attenuates LPS-in- duced nflammatory response in Caco2 cells. The inhibitory effect of osthole is independent on cAMP/PKA pathway. Osthole-induced reduction of phosphorylation of p38,Erk, and JNK may mediate its anti-inflammation action in Caco2 cells.

关 键 词：蛇床子素 脂多糖 炎症 MAPK Caco2细胞 

分 类 号：R282.5[医药卫生—中药学]