Maerz Stefanie, Liu Chun-Hua, Guo Wei, Zhu Yi-Zhun
Department of Pharmacology, School of Pharmacy and Institute of Biomedical Sciences, Fudan University, Shanghai, People's Republic of China.
Biosci Rep. 2011 Oct;31(5):439-47. doi: 10.1042/BSR20100128.
Terpene trilactones from Ginkgo biloba have been investigated extensively for their antioxidant and anti-ischaemic activities on the brain and the heart, but the mechanisms of these effects remain unclear. For the present study, a terpenoid constituent from G. biloba, bilobalide, was screened for protective effects on the ischaemic heart and the involvement of the PAFR [PAF (platelet-activating factor) receptor] and the enzyme that degrades PAF, PAF-AH (PAF acetylhydrolase) during hypoxia. The PAF pathway is supposed to play a role in hypoxia and its regulation may prevent or alleviate MI (myocardial infarction). Cardiomyocytes from neonatal rat hearts were cultured and treated with different concentrations of bilobalide (500-0.5 ng/ml). After being subjected to a hypoxic environment, the cells' viability was evaluated and proteins as well as RNA were extracted for analysis by Western blotting and RT-PCR (reverse transcription PCR) respectively. With the MI model we tested for bilobalide's cardioprotective effects and the involvement of PAFR and PAF-AH. Bilobalide (5 ng/ml) significantly decreased the mortality of cells in a concentration-dependent way. mRNA expression of PAFR was up-regulated in hypoxic cells but in the groups treated with bilobalide, its expression was down-regulated to the level of the normal control. In hypoxic tissue, PAFR protein expression was also up-regulated, but was reduced in the bilobalide (10 mg/kg of body weight) treated group. Our results indicate that PAF and its receptor may be involved in the cellular response of cardiomyocytes to hypoxia and that bilobalide may interact with this receptor to exert its cardioprotective effects.
银杏叶中的萜类三内酯因其对大脑和心脏的抗氧化及抗缺血活性而受到广泛研究，但其作用机制仍不清楚。在本研究中，对银杏叶中的一种萜类成分白果内酯进行了筛选，以研究其对缺血心脏的保护作用以及在缺氧过程中血小板活化因子受体（PAFR）[血小板活化因子（PAF）受体]和降解PAF的酶——PAF乙酰水解酶（PAF-AH）的参与情况。PAF途径被认为在缺氧中起作用，其调节可能预防或减轻心肌梗死（MI）。培养新生大鼠心脏的心肌细胞，并用不同浓度的白果内酯（500 - 0.5纳克/毫升）进行处理。在缺氧环境下处理后，评估细胞活力，并分别提取蛋白质和RNA，通过蛋白质印迹法和逆转录聚合酶链反应（RT-PCR）进行分析。利用MI模型测试白果内酯的心脏保护作用以及PAFR和PAF-AH的参与情况。白果内酯（5纳克/毫升）以浓度依赖的方式显著降低细胞死亡率。缺氧细胞中PAFR的mRNA表达上调，但在用白果内酯处理的组中，其表达下调至正常对照水平。在缺氧组织中，PAFR蛋白表达也上调，但在白果内酯（10毫克/千克体重）处理组中降低。我们的结果表明，PAF及其受体可能参与心肌细胞对缺氧的细胞反应，白果内酯可能与该受体相互作用以发挥其心脏保护作用。
