槲皮素在糖尿病模型大鼠肝脏甲基化代谢的研究

Hepatic methylation of quercetin in diabetes mellitus rats

目的:考察糖尿病模型大鼠体内槲皮素甲基化代谢的变化情况。方法:采用高脂高糖饮食+链脲佐菌素(STZ)诱导的糖尿病大鼠肝匀浆,研究槲皮素甲基化代谢特征及酶动力学,并与正常大鼠比较观察糖尿病状态下甲基化代谢的差异。结果:槲皮素(浓度2.6～165.5μM)在大鼠肝匀浆中甲基化代谢酶动力学符合Michaelis-Menten方程。槲皮素在正常和糖尿病大鼠肝匀浆的甲基化代谢的酶动力学参数米氏常数(Km)分别为12.4±2.6、12.0±0.7μM,最大反应速度(Vmax)分别为440.4±27.5、307.9±5.1pmol/min/mg,内在代谢清除率(CLint)分别为35.4、25.7 ml/min/mg。与正常大鼠相比,糖尿病大鼠肝匀浆中槲皮素甲基化代谢物的Vmax和CLint降低。结论:糖尿病状态降低了槲皮素甲基化代谢,可能会减慢槲皮素在体内的消除过程。

Objective： To investigate hepatic methylation of quercetin in diabetes mellitus rats.Methods： Quercetin was metabolized in vitro by liver homogenate in normal and streptozotocin induced diabetic rats.The substrate concentration vs time curve and enzyme kinetic parameters（Km,Vmax and Clint） of quercetin were estimated using liver homogenate.The differences of hepatic methylation of quercetin between normal and diabetes mellitus group were tested by T-test.Results： The kinetics of methylated quercetin formation by liver homogenate at 2.6-165.5 μM exhibited characteristics of typical Michaelis-Menten kinetics.Km values of methylated quercetin formation in normal and diabetic rats were 12.4 ±2.6,12.0 ±0.7μM,respectively.Vmax were 440.4 ±27.5,307.9±5.1 pmol/min/mg,respectively.Clint values were 35.4,25.7 ml/min/mg,respectively.Compared with normal rats,Vmax and Clint values were significantly reduced in diabetic rats（P〈0.05）.Conclusion： Methylation of quercetin was significantly decreased and the elimination of quercetin was slowed in diabetic status.