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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 effect of total alkaloids from Coptis chinensis on plasma endogenous substances and their metabolic status in diabetic patients by using metabolomics. Methods: Sixty normal SD rats were randomly divided into blank, model, positive drug group, Huanglian high dose group and Huanglian low dose group, with 10 rats in each group. The model group, the positive drug group and the Coptis high and low dose groups all used STZ diabetes model rats. After the successful model making, the positive drug group was given 100 mg / kg metformin, and the total dose of Coptidis Rhizoma alkaloids was 578.7 mg / kg Berberine 300 mg / kg), 192.9 mg / kg (berberine 100 mg / kg) orally administered Coptidis alkaloids. After continuous administration for 68 days, the orbital blood was collected and the data of plasma endogenous substances, PCA and OSC-PLS were collected for data analysis by HPLC / MS / MS. . RESULTS: After administration for 68 days, the levels of endogenous substances in the plasma of the rats treated with Coptis total alkaloids in high and low dose groups were significantly different from those in the model group. In each drug-treated group and the positive drug group, The content of endogenous substances in plasma of rats returned to the level of plasma in blank control rats in general, while there was no significant difference between the high and low doses of Coptis chinensis. Rat plasma m / z value of 496.4,524.5 and other endogenous compounds occur with the metabolic changes in the level of change in the direction. Conclusion: The total alkaloids of Coptis chinensis at doses of 578.7 mg / kg and 192.9 mg / kg can significantly affect the levels of endogenous substances in the plasma of model rats and cause the corresponding levels of endogenous substances to the normal rats Return to the horizontal direction.