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[摘要]
目的 研究复方丹参方及其单味药对大鼠心脏细胞色素P450酶(CYPs)主要亚型的影响。方法 雄性SD大鼠随机分为5组,分别用复方丹参方 [0.32 g/(kg?d)]、丹参 [0.27 g/(kg?d)]、三七 [0.05 g/(kg?d)]、冰片 [0.003 g/(kg?d)] 或生理盐水连续ig诱导处理28 d,取各组大鼠心脏组织,利用Real Time荧光定量PCR技术检测各组大鼠心脏CYPs各亚型mRNA表达水平的变化。结果 与对照组比较,复方丹参方对大鼠心脏CYP1B1、CYP2B1、CYP2E1、CYP4A1和CYP4F4的mRNA表达有下调趋势(P<0.05)。丹参对CYP1A1、CYP1B1、CYP2B1、CYP2C11、CYP2E1、CYP2J3、CYP4A1、CYP4F4和CYP4F5的mRNA表达有下调趋势(P<0.05、0.01),而对CYP4A3、CYP4F1和CYP4F6的mRNA表达有上调趋势(P<0.05)。三七对CYP1A1、CYP1B1、CYP2B1、CYP2C11、CYP2E1、CYP2J3、CYP4A1、CYP4A3、CYP4F4、CYP4F5和CYP4F6的mRNA表达均有不同程度的抑制趋势(P<0.05、0.01)。冰片对CYP1A1、CYP1B1、CYP2B1、CYP2C11、CYP4A1和CYP4F4的mRNA表达有下调作用(P<0.01)。结论 复方丹参方全方对心脏CYPs 亚型mRNA表达影响弱于方中各单味药对CYPs的影响,显示复方对CYPs影响可能是各单味药作用的综合和叠加,同时全方及单味药对CYP2家族和CYP4家族的影响显示其对心脏均有双向调节作用。
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[Abstract]
Objective To study the effects of Composite Salvia Recipe (CSR) and its single drugs on the main subtypes of cardiac cytochrome P450 (CYPs) in rats. Methods Male SD rats were randomly divided into five groups, CSR [0.32 g/(kg?d)], Salvia miltiorrhiza [0.27 g/(kg?d)], Panax notoginseng [0.05 g/(kg?d)], borneol [0.003 g/(kg?d)], and physiological saline were ig given for 28 d, then the cardiac tissues were taken. The mRNA expression change of cardiac CYPs was detected by real time PCR. Results Compared with the control group, CSR could down-regulate the mRNA expression of CYP1B1, CYP2B1, CYP2E1, CYP4A1, and CYP4F4 (P < 0.05). S. miltiorrhiza could significantly down-regulate the mRNA expression of CYP1A1, CYP1B1, CYP2B1, CYP2C11, CYP2E1, CYP2J3, CYP4A1, CYP4F4, and CYP4F5 (P < 0.05, 0.01), while up-regulate the mRNA expression of CYP4A3, CYP4F1, and CYP4F6 (P < 0.05). P. notoginseng inhibited the mRNA expression of CYP1A1, CYP1B1, CYP2B1, CYP2C11, CYP2E1, CYP2J3, CYP4A1, CYP4A3, CYP4F4, CYP4F5, and CYP4F6 (P < 0.05, 0.01); Borneol could inhibit the mRNA expression of CYP1A1, CYP1B1, CYP2B1, CYP2C11, CYP4A1, and CYP4F4 (P < 0.01). Conclusion The study declares that the single drugs have more significant influences on the mRNA expression of CYP than CSR. CSR and its single drugs might protect heart, and its effect on CYP2 and CYP4 families might be bidirection regulation.
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[基金项目]
国家重点基础研究发展计划(“973”计划)资助项目(2012CB518402)