隐丹参酮对IGF-1促PC12细胞存活的作用及机制探讨  

Influence and Possible Mechanisms of Cryptotanshinone on the Survival of PC12 Cells Promoted by IGF-1

作　　者：孟茜[1] 郑文华[1] 

机构地区：[1]中山大学药学院,广州510006

出　　处：《中国实验方剂学杂志》2013年第10期195-198,共4页Chinese Journal of Experimental Traditional Medical Formulae

基　　金：国家自然科学基金资助项目(30711120565)

摘　　要：目的:研究隐丹参酮对类胰岛素样生长因子-1(IGF-1)促进PC12细胞存活的影响及可能机制。方法:首先采用剥夺血清造成细胞损伤模型确定IGF-1发挥促存活作用的剂量,然后不同剂量的隐丹参酮预先作用PC12细胞,再加入IGF-1处理,MTT检测隐丹参酮对IGF-1促PC12细胞存活的影响;Western blot检测隐丹参酮对IGF-1诱导其受体(IGF-1R)磷酸化及下游信号通路磷酯酰肌醇-3-激酶(PI3K)/蛋白激酶B(Akt)及细胞外信号调节激酶(ERK)1/2的影响。结果:MTT显示隐丹参酮能剂量依赖性地阻断IGF-1的促存活作用,抑制PC12细胞的增殖;Western blot结果显示IGF-1能明显诱导其受体(IGF-1R)磷酸化,而隐丹参酮则起抑制作用,并使下游Akt及ERK1/2的磷酸化水平下调,呈明显的剂量依赖性。结论:隐丹参酮可通过抑制IGF-1R及其下游信号分子Akt和ERK1/2的磷酸化,从而抑制IGF-1的促存活功能,发挥其自身抑制细胞存活,促使细胞凋亡的作用。Objective： Study the effect of cryptotanshinone（CTS） on the survival of in PC12 cells promoted by insulin-like growth factor-1（IGF-1） and possible mechanisms. Method： The serum deprivation model was constructed to determine the dose of IGF-1 to play the survival-promoting effect, then pretreat PC12 cells with different concentrations of CTS, then treated with IGF-1 processing 24 hours, MTT assay was used to detect the effect of CTS on protective function of IGF-1.The effect of CTS and IGF-1 on the phosphorylation level of IGF-1 receptar（IGF-1R） were analyzed by Western blot and downstream targets were also detected such as protein kinase B（Akt） and extracellular signal regulated kinase（ERK）. Result： After treatment with IGF-1, cell viability of PC12 cells was increased in a dose-dependent manner as same as the phosphorylation level of IGF-1R, whereas CTS attenuated the survival promoting effect of IGF-1 in PC12 cells and decreased the phosphorylated IGF-1R. Moreover, CTS attenuated the phosphorylation of Akt and ERK1/2 induced by IGF-1in a dose-dependent manner. Conclusion： These data indicate that CTS has an inhibitory effect on PC12 cells viability via down-regulate the phosphorylation of IGF-1R and downstream Akt and ERK.

关 键 词：隐丹参酮 PC12细胞 类胰岛素样生长因子-1受体 蛋白激酶B 细胞外信号调节激酶1 2 

分 类 号：R285.5[医药卫生—中药学]