急性心肌缺血对丹参素在大鼠体内甲基化代谢的影响

Effect of acute myocardial ischemia on methylation of danshensu in rats

目的:考察急性心肌缺血对丹参素在大鼠体内甲基化代谢的影响。方法:结扎大鼠冠状动脉左前降支造成急性心肌缺血模型。药动学和组织分布研究中,正常和急性心肌缺血大鼠分别静脉注射丹参素和丹参注射液,血浆药动学研究中增设托卡朋合用丹参素组。用HPLC方法测定血浆和心,肝,肾,肺等组织中丹参素及其单氧甲基化代谢物的浓度。结果:静脉注射丹参素后,正常和心肌缺血大鼠血浆中丹参素单氧甲基化代谢物的AUC分别为(2.12±0.39)μg.h/mL和(5.28±0.82)μg·h/mL,MRT分别为(0.69±0.21)h和(1.35±0.16)h;注射丹参注射液后,甲基化代谢物在血浆中AUC分别为(1.64±0.20)μg.h/mL和(3.98±0.40)μg·h/mL,MRT分别为(0.76±0.16)h和(1.07±0.19)h。与正常大鼠相比,急性心肌缺血大鼠心脏中甲基化代谢物的浓度显著降低。45 min时急性心肌缺血大鼠体内几乎所有组织甲基化代谢物的浓度显著高于正常大鼠中的相应值。结论:急性心肌缺血显著影响了丹参素单氧甲基化代谢物在血浆和心脏中的分布水平,减慢了甲基化代谢物体内消除过程。

Aim： To evaluate the effect of acute myocardial ischemia （AMI） on methylation of danshensu （DSS） in rats. Methods： AMI were induced by occlusion of the left anterior descending coronary artery. 12 normal and 12 AMI rats were respectively divided into DSS group and danshen injection group. In the pharmaeokinetic study in plasma, 6 normal male rats were added as DSS ± tolcapone group. Plasma and tissue levels of DSS and its mono-O-methylation metabolite were determined by HPLC. Results： Following intravenous administration of DSS, AUC of mono-O-methyl DSS in plasma of normal and AMI rats were （2. 12 ± 0. 39） μg· h/mLand （5.28 ±0.82）μg h/mL, respectively. MRT were （0. 69 ±0. 21） h and （ 1.35 ±0. 16） h, respectively. Compared with normal rats, concentration of mono-O-methyl DSS in hearts of AMI rats were significantly reduced. 45 min after administration in AMI rats, concentrations of mono-O-methyl DSS in most tissues were significantly higher than those in tissues of normal rats. Conclusion： Methylation of DSS in plasma and heart were significantly influenced by AMI status. At the same time, the elimination of mono-O-methyl DSS was greatly slowed.