黄连总生物碱对糖尿病大鼠的血浆代谢组学研究

Metabonomics study on the plasma of diabetes rats administrated with total alkaloids from Rhizoma Coptidis

目的:应用代谢组学的方法研究黄连总生物碱对糖尿病血浆中内源性物质及其代谢状态的影响。方法:60只正常SD大鼠随机分为空白、模型、阳性药物组、黄连高剂量组、黄连低剂量组,每组10只。模型组,阳性药物组,黄连高低剂量组均使用STZ造糖尿病模型大鼠,造模成功后,阳性药物组给予100 mg/kg二甲双胍,黄连总生物碱大小剂量分别按578.7 mg/kg(含小檗碱300 mg/kg),192.9 mg/kg(含小檗碱100 mg/kg)口服灌胃给予黄连总生物碱。大鼠连续给药68 d后,眼眶取血,HPLC/MS/MS采集血浆中内源性物质数据,主成分分析(PCA),正交信号校正偏最小二乘法(OSC-PLS)对数据分析。结果:给药68 d后,黄连总生物碱高低剂量给药组,阳性药物组大鼠血浆中内源性物质的含量水平与模型组具有明显的差异,各给药组及阳性药物组中,大鼠血浆中内源性物质的含量水平总体向空白对照大鼠组血浆中含量水平方向回归,黄连高低剂量组间差异不明显。大鼠血浆中m/z值496.4,524.5等内源性化合物发生了与其代谢含量水平改变方向一致的变化。结论:黄连总生物碱剂量为578.7 mg/kg和192.9mg/kg均能明显影响模型大鼠血浆中内源性物质的含量水平,并引起相应的内源性物质含量水平向正常组大鼠含量水平方向回归。

Objective： To study the of the plasma of diabetes rats administrated with total alkaloids from Rhizoma Coptidis. Methods： The diabetic rats model was established by single intraperitoneal injection of streptozotocin 50 mg/kg. The fasting time of diabetic rat model was screened. SD rats had been successively administrated total alkaloids from Rhizoma Coptidis （ 578.7mg/kg and 192.9 mg/kg ） for 68 days. Plasma was acquired,then detected by LC/MS/MS, at last data was analyzed by PCA, OSC-PLS. Results： The diabetes rats administrated with total alkaloids after 68 d, there was obvious difference in the content of endogenous substances among the positive drug group and the two administrated groups, the overall content level of endogenous substances in the two groups returned to that of the control group, but the difference of that between the two administrated groups was not obvious. The endogenous substances m/z values as 496.4,524.5 the potential biomakers. Conclusion： The total alkaloids（578.7mg/kg and 192.9 mg/kg） could significantly influence the content of endogenous substances in plasma in diabetes rats, and caused the content level corresponding endogenous substance and return in the direction of control group levels in rats.