丹参素对大鼠肝星状细胞氨基末端蛋白激酶信号转导的影响  

Effect of danshensu on activation of JNK pathway in hepatic stellate cells（HSCs） induced by IL-1 beta

作　　者：余斌斌[1] 戴立里[1] 李欣[1] 李冬[1] 姜中华[1] 

机构地区：[1]重庆医科大学附属第二医院消化内科,400010

出　　处：《中华肝脏病杂志》2009年第6期451-454,共4页Chinese Journal of Hepatology

摘　　要：目的探讨丹参素抗肝纤维化作用的机制。方法分离大鼠原代肝星状细胞（HSC），用0．0312、0．0625、0．1250、0．2500、0．5000、1．0000mmol／L不同浓度丹参素作用于HSC，四甲基偶氮唑盐法检测丹参素对HSC生长增殖的抑制作用；应用免疫细胞化学法观察Ⅰ型胶原合成，酶联免疫吸附法观察Ⅰ型胶原分泌。Westernblot法观察丹参素对白细胞介素-1β（IL-1β）刺激的HSC内氨基末端蛋白激酶（JNK）蛋白及其磷酸化表达的影响。采用随机设计的方差分析，SNK-q进行统计学处理。结果与0mmol／L组比较，丹参素其他浓度组明显抑制了HSC增殖，并呈剂量依赖性。丹参素（0．0625～0．2500retool／L）对IL-1β引起的HSC增殖具有明显的抑制作用，并呈剂量依赖性。0．25mmol／L丹参素对正常培养的和经IL-1β刺激的HSC作用24h能下调Ⅰ型胶原的合成和分泌。IL-1β能刺激HSC中P-JNK的明显表达，丹参素能下调IL-1β诱导的HSC中P-JNK的表达，但其对JNK表达水平没有明显影响。结论丹参素可抑制正常传代培养的和经IL-1β刺激的大鼠HSC增殖、Ⅰ型胶原合成与分泌，其机制可能与抑制JNK信号转导通路有关。Objective To investigate the inhibitory effect of danshensu on the activation of JNK signaling in rat hepatic stellate cells （HSCs） induced by IL-1β. Methods The proliferation of primary rat HSCs treated with different concentration of Danshensu was checked by MTT colorimetric assay. The expression and phosphorylation of JNK and P-JNK was detected by western blotting. Synthesis and secretion of collagen Ⅰ were detected by the quantitative immunocytochemical assay and ELISA. Results Danshensu inhibited the proliferation of HSCs in a dose-dependent manner. At the concentration of 0.0625 to 0.25 mmol/L, Danshensu significantly repressed the proliferation of HSC induced by IL-1 β （P 〈 0.05）. Synthesis and secretion of Type Ⅰ collagen was significantly decreased 24 hours after 0.25 mmol/L Danshensu treatment （P 〈 0.01）. The phosphorylation of JNK induced by IL-1β was significantly inhibited by Danshensu treatment （P 〈 0.05）, however, the expression of JNK was not regulated by Danshensu. Conclutions Danshensu represses the activation and proliferation of HSCs, and inhibits the synthesis and secretion of Type Ⅰ collagen, possibly via the repression of the JNK signal transduction.

关 键 词：肝纤维化 肝星状细胞 信号转导 白细胞介素-1 丹参素 

分 类 号：R285.5[医药卫生—中药学]