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目的:应用血清代谢组学方法探讨三七总皂苷(PNS)对早期的顺铂肾损害大鼠的保护作用。方法:顺铂组大鼠单剂量腹腔注射顺铂,PNS干预组大鼠注射顺铂后再腹腔注射PNS,每天1次。24 h后,评价大鼠肾功能,苏木精-伊红染色(HE)观察肾脏组织病理学的改变,并使用核磁共振代谢组学技术进行血清代谢组学的检查。结果:PNS可降低血清肌酐(SCr),血尿素氮(BUN)的浓度和改善肾组织病理损伤。另外,血清标本的主成分分析(PCA),偏最小二乘法判别分析(PLSDA)和正交偏最小二乘法判别(OPLS-DA)分析显示,顺铂模型组,PNS干预组均与正常组有显著的区分,而顺铂模型组与PNS干预组之间有部分重叠。与正常组比较,顺铂模型组和PNS干预组的丙酮,n-乙酰糖蛋白信号,丙酮酸,脂质和极低密度脂蛋白(VLDL)表达降低,而葡萄糖、缬氨酸和酪氨酸的表达升高。而且,顺铂模型组的乳酸表达较PNS干预组高。另外,正常组和PNS干预组大鼠苯丙氨酸的表达较顺铂模型组高,而酪氨酸的表达较顺铂模型组低。差异代谢物涉及的代谢通路主要有戊糖磷酸途径、糖酵解/糖异生途径、丙酮酸途径等与能量代谢相关的通路。结论:PNS对顺铂肾毒性有保护作用,其保护机制可能和逆转顺铂肾损害引起的代谢紊乱尤其是能量代谢障碍有关。
Objective: To explore the protective effect of Panax Notoginseng Saponins (PNS) on early renal damage of cisplatin in rats by serum metabolomics. Methods: Rats in Cisplatin group were injected intraperitoneally with Cisplatin. PNS group was given intraperitoneal injection of cisplatin (PNS) once a day. After 24 hours, the renal function of rats was evaluated. The pathological changes of kidney were observed by hematoxylin-eosin staining (HE). The serum metabolomics was examined by using nuclear magnetic resonance metabonomics. Results: PNS decreased serum creatinine (SCr), blood urea nitrogen (BUN) and renal tissue pathological damage. In addition, principal component analysis (PCA), partial least-squares discriminant analysis (PLSDA) and orthogonal partial least squares (OPLS-DA) analysis of serum samples showed that cisplatin model group and PNS intervention group had There was a significant difference between the cisplatin model group and the PNS intervention group. Compared with the normal group, the expressions of acetone, n-acetylglucosidase, pyruvate, lipids and VLDL decreased in the cisplatin model group and the PNS intervention group, while glucose, valine and tyrosine Increased expression. Moreover, lactic acid expression in the cisplatin model group was higher than that in the PNS intervention group. In addition, the expression of phenylalanine in normal group and PNS intervention group was higher than that in cisplatin model group, while tyrosine expression was lower in cisplatin model group. Differential metabolites involved in the metabolic pathways are pentose phosphate pathway, glycolytic / gluconeogenic pathway, pyruvate pathway and energy metabolism-related pathways. Conclusion: PNS has a protective effect on cisplatin nephrotoxicity, and its protective mechanism may be related to the reversal of metabolic disorders caused by cisplatin and renal damage, especially energy metabolism disorder.