Tu Jiayu, A Jiye, Wang Guangji, Wen Hongmei, Wang Aiyun, Di Liuqing, Cao Bei, Liu Linsheng
School of Pharmacy, Nanjing University of Chinese Medicine, Nanjing 210029, China.
Zhongguo Zhong Yao Za Zhi. 2012 Apr;37(7):1028-33.
To observe abnormal metabolic changes caused by ischemic cerebral apoplexy and the regulating action of Tongsaimai pellets on abnormal metabolism by analyzing the change of small molecules in plasma of ischemic cerebral apoplexy rat. To find the potential biomarkers, and to explore metabolic mechanisms of Tongsaimai pellets.
Rat models of middle cerebral artery occlusion was established with electric coagulation, and rats were divided into 4 groups, model group, sham-operation group, Tongsaimai pellets group and positive control group. Tongsaimai pellets and positive control group were orally administrated by 13.2 g x kg(-1) x d(-1) of crude drugs and 32 mg x kg(-1) x d(-1) of Nimodipine respectively, m odel and sham-operation group by equal volume of distilled water for a week. Plasma of model and sham-operation group were collected, and plasma of Tongsaimai pellets and positive control group were collected on the 1st, 3rd , 7th day after administration. Endogenous metabolites of four groups were determined with GC-MS. Partial least squares discriminant analysis (PLS-DA) was applied to analyze multivariate data and set up model, and T-test was used in significant statistical analysis.
Compared with sham-operation group rats, pyruvic acid, taurine and hydroxyproline obviously increased in model group rats, while lactic acid, glyceric acid, aminomalonic acid, fructose, tryptophan and leucine significantly decreased, so these metabolites were potential metabolic biomarkers. These endogenous metabolites except taurine got restoration in Tongsaimai group rats.
Abnormal metabolite level in plasma can be certainly recovered by Tongsaimai pellets, and the treatment of Tongsaimai pellets can be connected with the regulation of related metabolic pathways.
通过分析缺血性脑中风大鼠血浆中小分子物质的变化,观察缺血性脑中风引起的异常代谢变化以及通塞脉颗粒对异常代谢的调节作用。寻找潜在的生物标志物,探讨通塞脉颗粒的代谢机制。
采用电凝法建立大脑中动脉闭塞大鼠模型,将大鼠分为4组,即模型组、假手术组、通塞脉颗粒组和阳性对照组。通塞脉颗粒组和阳性对照组分别按13.2 g·kg⁻¹·d⁻¹的生药量和32 mg·kg⁻¹·d⁻¹的尼莫地平灌胃给药,模型组和假手术组给予等体积蒸馏水,连续给药1周。收集模型组和假手术组大鼠的血浆,通塞脉颗粒组和阳性对照组在给药后第1、3、7天收集血浆。采用气相色谱-质谱联用仪测定4组大鼠的内源性代谢产物。应用偏最小二乘法判别分析(PLS-DA)对多变量数据进行分析并建立模型,采用t检验进行显著性统计分析。
与假手术组大鼠相比,模型组大鼠丙酮酸、牛磺酸和羟脯氨酸明显升高,而乳酸、甘油酸、氨基丙二酸、果糖、色氨酸和亮氨酸显著降低,因此这些代谢产物是潜在的代谢生物标志物。通塞脉颗粒组大鼠除牛磺酸外,这些内源性代谢产物均恢复正常。
通塞脉颗粒可使血浆中异常代谢产物水平得到一定程度的恢复,通塞脉颗粒的治疗作用可能与相关代谢途径的调节有关。