银杏内酯、刺五加皂苷和人参皂苷诱导PC12细胞缺氧诱导因子-1α表达

Influence of ginkgolides, Acanthopanax senticosus saponins and ginsenosides on expression of hypoxic inducible factor-1α in neural cells

目的缺氧诱导因子-1α(HIF-1α)在介导心肌和脑低氧/缺血的适应性反应中起重要作用,本文研究银杏内酯、刺五加皂苷和人参皂苷的药理作用机制是否与HIF-1α表达及其相关信号通路有关。方法MTT比色法观察PC12细胞活性,蛋白质免疫印迹法分析PC12细胞HIF-1α及磷酸化细胞外信号调节激酶1/2(p-ERK1/2)蛋白表达,RT-PCR观察HIF-1αmRNA表达。结果一定浓度范围的银杏内酯、刺五加皂苷或人参皂苷均可促进PC12细胞的活性,在浓度分别为37.5,50和60mg·L-1时达最好效果;银杏内酯(37.5mg·L-1)、刺五加皂苷(50mg·L-1)或人参皂苷(60mg·L-1)处理PC12细胞24h均可诱导p-ERK1/2和HIF-1α表达增高,且引起HIF-1αmRNA表达水平的上调,提示HIF-1α蛋白水平的增高与其合成增加有关。结论银杏内酯、刺五加皂苷和人参皂苷均可诱导PC12细胞表达HIF-1α,该作用可能与激活MAPK信号通路有关。

AIM Hypoxic inducible factor-1α （HIF-1α） plays an important role in the adaptive responses to myocardial and brain hypoxia/is chemia. Whether the pharmacological mechanism of ginkgolides （ Gin ）, Acarahopanax seraicosus saponins （As）, ginsenosides （Gs） are related to the expression of HIF-1α and the signaling pathways involved was studied in this paper. METHODS The viability of PC12 cells was determined by MTT assay. The expression of HIF-1α and phospho-ERK1/2 （p-ERK1/2） were detected by Western blot. The expression of HIF-1α mRNA was detected by RT-PCR. RFSULTS Gin, As and Gs enhanced the viability of PC12 cells in some ranges of concentration and reached the peak effect at the concentration of 37.5, 50 and 60 mg·L^-1, respectively. Gin （37.5 mg·L^-1 ）, As （50mg·L^-1） and Gs （60mg·L^-1） enhanced both p-ERK1/2 and HIF-1α expression significantly after treating PC12 cells for 24 h. They also increased HIF-1α mRNA expression, suggesting that the increase in HIF-1α protein level result from the synthesis. CONCLUSION Gin, As and Gs can induce the expression of HIF-1α in PC12 cells, which may be related to the activation of MAPK signal pathway.