三七总皂苷对H9c2细胞P450酶mRNA表达的影响  

Effect of Panax notoginseng saponin on cytochrome P450 mRNA expression in H9c2 cell

作　　者：胡东华[1,2] 王宇光[1] 陈志武[2] 马增春[1] 梁乾德[1] 肖成荣[1] 谭洪玲[1] 汤响林[1] 高月[1] 

机构地区：[1]军事医学科学院放射医学研究所药理毒理研究室,北京100850 [2]安徽医科大学药理学教研室,安徽合肥230032

出　　处：《中国药理学通报》2013年第11期1563-1567,共5页Chinese Pharmacological Bulletin

基　　金：国家自然科学基金资助项目(No 81073149);国家重点基础研究发展计划(973计划)资助项目(No 2011CB505304;2012CB518402);国家"重大新药创制"注射用血栓通安全性评价和作用机制研究项目资助(No 2012ZX09101201-006)

摘　　要：目的研究三七总皂苷(PNS)对H9c2心肌细胞P450酶主要亚型表达的影响。方法不同浓度的PNS处理H9c2细胞48h,MTS法检测细胞的存活率,测定LDH释放率评价细胞损伤程度,Real Time PCR法检测PNS各处理组对CYP450酶各亚型mRNA表达的变化。结果 MTS结果表明随着PNS浓度的增大,细胞的存活率逐渐降低并呈浓度依赖性,IC50(5.28±0.08)g·L-1,同时LDH的释放率也逐渐增大。在对P450酶mRNA表达影响层面,PNS使CYP2J3、CYP4A1、CYP4A2、CYP4F1和CYP4F5表达上调(P<0.05或P<0.01);对CYP2C11、CYP4A3和CYP4F4表达下调(P<0.05或P<0.01),但高浓度时(5 g·L-1)对CYP4A3和CYP4F4有上调作用(P<0.01)。结论 PNS对心脏和血管有一定的保护作用,高浓度(5 g·L-1)的PNS对H9c2细胞有一定细胞毒作用,因此使用PNS时应注意用药剂量,使其发挥疗效而尽量减少药物不良反应的发生。Aim To study the effect of Panax notogin- seng saponin on cytochrome P450 mRNA expression in H9c2 cell. Methods H9c2 cells were treated with different concentrations of PNS for 48h. Cell viability was examined by MTS assay kit cell membrane injury was examined by detecting the release rate of lactate dehydrogenase（LDH）. The expression of cytocbrome P450 mRNA was detected by Real Time PCR. Results H9c2 cell viability significantly reduced following exposure to dictamnine 0. 3125 -20 g · L^-1 for 48h in a concentration-dependent manner and ICs0 value was （5.28±0.08）g· L^-1. The LDH release rate of H9c2 cells significantly increased after exposure to dictamnine 0. 3125 - 20 g · L^-1 for 48h （P〈0.01）. On the mRNA level, compared with the control group, PNS induced the mRNA level of CYP2J3, CYP4A1, CYP4A2, CYP4F1 and CYP4F5（P 〈0.05 or P 〈 0. 01）. PNS had inhibitory activity of CYP2C11, CYP4A3 and CYP4F4（P 〈0.05 or P 〈0. 01 ）, while had inductive effects on mRNA of CYP4A3 and CYP4F4（P 〈0.01 ） at 5 g · L^-1. Conclusion These results indicate that PNS at higher concentrations has potentioal hepatotoxicity. PNS had different effects on the mRNA level of CYP in different concentrations. It might protect heart and blood vessel. Doses of medication should be more careful when PNS is used in clinic.

关 键 词：PNS 血栓通 H9C2 CYP450 细胞毒性 用药剂量 

分 类 号：R284.1[医药卫生—中药学] R322.11[医药卫生—中医学]