石榴皮鞣质对慢性肾小球肾炎大鼠内源性代谢物的影响

Effects of tannins in pomegranate rind on endogenous metabolites in rats with chronic glomerulonephritis

目的:运用代谢组学方法考察石榴皮鞣质对慢性肾小球肾炎大鼠尿液内源性物质代谢的影响,寻找潜在的生物标志物并分析代谢途径,为慢性肾小球肾炎的治疗和石榴皮鞣质的利用提供相关理论依据。方法:SD大鼠随机分为5组,正常对照组、模型组、阳性对照组、石榴皮鞣质高剂量组、低剂量组。除正常对照组,其余各组均采取大鼠尾静脉注射阳离子化牛血清白蛋白(C-BSA)构建大鼠慢性肾小球肾炎(CGN)模型。收集各组大鼠术后3周尿样,经预处理后,进行液相色谱-高分辨质谱分析,获得总离子流图。对LC-MS所得数据进行预处理,导入SIMCA-P软件进行主成分分析(PCA)和偏最小二乘法判别分析(PLS-DA),根据获得的得分图、载荷图以及VIP值的分析结果,寻找潜在的生物标志物。结果:代谢组学分析发现造模后第3周各组大鼠尿液有明显的聚类现象,通过对重要变量的分析鉴定,筛选出12个潜在的生物标志物。结论:石榴皮鞣质干预下的慢性肾小球肾炎大鼠内源性代谢物聚类性趋近正常水平,代谢组学分析法寻找潜在生物标志物可行且有效。

OBJECTIVE To study on influences of tannins of pomegranate rind on metabolism of endogenous substances in rats with chronic glomerulonephritis by using metabonomics method, to excavate potential biomarkers and analyze metabolic pathways, and provide relevant theoretical knowledge on treatment of chrOnic glomerulonephritis and utilization of tannins from pomegranate. METHODS SD rats were randomly divided into five groups： normal group, model group, control group, high- dose and low-dose of pomegranate tannins groups. The rat model of CGN was established by injecting C-BSA into tail vein. U- rine of rats was collected after 3 weeks, after pretreatment, and liquid chromatography-high resolution mass spectrometry was used to obtain total ion current. For LC-MS data obtained pretreatment, SIMCA-P software was adopted from principal compo- nent analysis （PCA） and partial least squares discriminant analysis （PLS-DA）. Potential biomarkers were searched based on the score obtained chart, diagrams and VIP value load analysis results. RESULTS Results of metabolomics analysis showed that the urine of rats was clustering. Through analysis and identification of important variables, 12 potential biomarkers were screened. CONCLUSION The distribution of endogenous metabolites of rats with chronic glomerulonephritis tends to be nor- mal after intervention of tannins from pomegranate rind. It is feasible and effective to search potential biomarkers by using metabolomics method.