Analysis of the restorative effect of Bu-zhong-yi-qi-tang in the spleen-qi deficiency rat model using 1H-NMR-based metabonomics
Analysis of the restorative effect of Bu-zhong-yi-qi-tang in the spleen-qi deficiency rat model using 1H-NMR-based metabonomics
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DOI：
10.1016/j.jep.2013.12.001
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发表时间：
2014-02-03
影响因子：
5.4
通讯作者：
Qin, Xue-mei
中科院分区：
文献类型：
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作者：
Zheng, Xiao-fen;Tian, Jun-sheng;Qin, Xue-mei
民族药理相关性：补中益气汤是中医治疗脾气虚、脾虚内脏下垂、子宫脱垂、直肠脱垂等慢性腹泻的经典方剂，在临床上已被确定为治疗脾气虚证的有效药物。为探讨补中益气汤对大鼠脾气虚证模型的恢复作用及其可能机制。材料与方法：建立大鼠脾气虚证模型：口服大黄提取物(相当于生药10g/kg体重)、负重游泳、饥饿24 h，每隔3天连续给药一次。雄性SD大鼠60只，随机分为5组，其中3组在3周实验期的最后7天给予不同剂量的补中益气汤水提物灌胃。每周测量并记录大鼠的体重和运动行为。用核磁共振结合多元统计技术分析血浆中的内源性代谢物。结果：脾气虚组大鼠除体重、脾重、肝脏重量明显下降外，均出现大便变稀、活动不活跃、分组，游泳耐力下降，行为平淡、松散、无序等现象。补中益气汤治疗组大鼠上述指标与模型组相比有不同程度的逆转(p<；0.05，p<；0.01)。主成分分析结果显示，模型组与对照组有显著差异，表明脾气虚证模型复制成功。脾气虚组大鼠血浆内源性代谢产物水平的变化主要表现为血浆缬氨酸、亮氨酸、O-乙酰-糖蛋白水平降低，乳酸水平升高。结论：补中益气汤对脾气虚证大鼠具有一定的恢复作用，4种内源性代谢物可能是脾气虚证的潜在生物标志物，并可能参与能量代谢、蛋白质代谢、糖酵解代谢等代谢途径的改变。(C)2013爱思唯尔爱尔兰有限公司。保留所有权利。
Ethnopharmacological relevance: Bu-zhong-yi-qi-tang (BT) is a classical formula for the treatment of spleen-qi descending, visceroptosis with hyposplenic qi, uterine prolapse, and rectal prolapse due to chronic diarrhea in traditional Chinese medicine (TCM) and has been identified as an effective drug for the treatment of TCM spleen-qi deficiency in clinical practice. The present study aimed to investigate the restorative effect and the potential mechanisms of Bu-zhong-yi-qi-tang in a rat spleen-qi deficiency model using H-1-NMR-based metabonomics.Materials and methods: The rat spleen-qi deficiency model was established as follows: oral administration of Radix Rhei extract (equivalent to 10 g/kg body weight of the crude drug), loaded swimming, and starvation for 24 h. Each of these treatments was administered consecutively every three days. Sixty male SD rats were randomly divided into five groups, and three of the groups received a different oral dose of the aqueous extract of Bu-zhong-yi-qi-tang during the last seven days of the three-week experimental period. The body weight and motor behavior of the rats were measured and recorded once a week. The endogenous metabolites in the plasma were analyzed using NMR in conjunction with multivariate and statistical techniques. In addition, the liver and spleen were removed and weighed.Results: All of the rats in the spleen-qi deficiency group presented pasty loose stools, inactiveness, grouping, a decrease in swimming endurance, and lackluster, loose, and disorderly behavior in addition to a significant decrease in body weight, spleen weight, and liver weight. In contrast, the above-mentioned demonstrations were reversed to a certain extent in the rats treated with Bu-zhong-yi-qi-tang compared with the model group (p < 0.05, p < 0.01). A significant separation was determined between the control and model groups in the PCA score plot, which indicates that the spleen-qi deficiency model was successfully duplicated. The changes in the levels of endogenous metabolites in the plasma included lower levels of valine, leucine, and O-acetyl-glycoprotein and a higher Concentration of lactate in the spleen-qi deficiency group compared with the control group. Treatment with Bu-zhong-yi-qi-tang at least partially returned the levels of these metabolites to the normal levels.Conclusions: The restorative effects of Bu-zhong-yi-qi-tang in rats with spleen-qi deficiency were confirmed, and four endogenous metabolites were identified as potential biomarkers of the symptoms of spleen-qi deficiency and most likely play roles in the changes observed in certain metabolic pathways, such as the energy, protein, and glycolytic metabolisms. (C) 2013 Elsevier Ireland Ltd. All rights reserved.