雷公藤致大鼠肝脏、肾脏和心脏组织中代谢变化的研究
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摘要
目的基于组织代谢组学方法的气相色谱-质谱(GC-MS)来评估雷公藤对大鼠的影响。方法 30只大鼠随机分为雷公藤低剂量组、雷公藤高剂量组和对照组。低剂量组、高剂量组大鼠每天灌胃给药0.5 g/kg和1.0 g/kg的雷公藤,连续7 d;对照组给予生理盐水,连续灌胃7 d。用偏最小二乘法分析(PLS-DA)显示雷公藤诱导代谢扰动。结果与对照组相比,低剂量组大鼠肝脏中十六酸、肾脏中d-核糖以及心脏中d-葡萄糖含量均升高,肾脏和心脏中十六酸含量均降低;高剂量组大鼠肾脏中L-苏氨酸含量和心脏中L-脯氨酸、9H-嘌呤、十六酸、L-脯氨酸含量与对照组相比均降低。结论 PLS-DA结果表明,GC-MS代谢组学方法可以区分对照组和雷公藤组大鼠代谢情况的差异。代谢物的增加或减少表明雷公藤可诱导大鼠能量代谢、氨基酸代谢和脂质代谢紊乱。
Objective In this study, we developed a tissue metabolomic method by gas chromatography-mass spectrometry(GC-MS) to evaluate the effect of Tripterygium wilfordii(TW) on rats. Methods Thirty rats were randomly divided into TW groups(the higher dose group and the lower dose group) and control group. The rats in TW groups were respectively given 0.5 g/kg(low dose) and 1.0 g/kg(high dose) of TW by intragastric administration each day for continuous 7 days. The control group was given normal saline for 7 days. Results Partial least squares-discriminate analysis(PLS-DA) revealed that TW induced metabolic perturbations in rats. Compared to the control group, hexadecanoic acid, d-ribose and d-glucose increased in livers, kidneys and hearts of rats, respectively; and the hexadecanoic acid decreased in both kidneys and hearts of rats in lower dose group. Compared to the control group, L-threonine decreased in kidneys, and L-proline, 9 H-purine and L-proline decreased in hearts of rats in high dose group. Conclusion PLS-DA results indicated that metabolomic method by GC-MS could differentiate these rats in the control group and TW groups. The changes of metabolites(increased or decreased) can indicate that TW could induce energy metabolism, amino acid metabolism and lipid metabolism perturbations in tissues of rats.
Objective In this study, we developed a tissue metabolomic method by gas chromatography-mass spectrometry(GC-MS) to evaluate the effect of Tripterygium wilfordii(TW) on rats. Methods Thirty rats were randomly divided into TW groups(the higher dose group and the lower dose group) and control group. The rats in TW groups were respectively given 0.5 g/kg(low dose) and 1.0 g/kg(high dose) of TW by intragastric administration each day for continuous 7 days. The control group was given normal saline for 7 days. Results Partial least squares-discriminate analysis(PLS-DA) revealed that TW induced metabolic perturbations in rats. Compared to the control group, hexadecanoic acid, d-ribose and d-glucose increased in livers, kidneys and hearts of rats, respectively; and the hexadecanoic acid decreased in both kidneys and hearts of rats in lower dose group. Compared to the control group, L-threonine decreased in kidneys, and L-proline, 9 H-purine and L-proline decreased in hearts of rats in high dose group. Conclusion PLS-DA results indicated that metabolomic method by GC-MS could differentiate these rats in the control group and TW groups. The changes of metabolites(increased or decreased) can indicate that TW could induce energy metabolism, amino acid metabolism and lipid metabolism perturbations in tissues of rats.
引文
[1] 赵子北. 雷公藤的药理作用及临床应用[J]. 中国保健营养, 2017, 27(2): 103-103.
[2] 李云鹃, 罗花, 黄丽贞, 等. 雷公藤的毒性机理及减毒方法研究进展[J]. 中华中医药杂志, 2017,32(6):2612-2614.
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[6] 汪思媛, 赵星阳, 徐玮蔚, 等. 基于质谱技术的细胞代谢组学研究进展[J]. 中国细胞生物学学报, 2017, 39(8): 1130-1134.
[7] Wang C, Li CJ, Ma J, et al. Bioactive sesquiterpene polyol esters from the leaves of tripterygium wilfordii[J]. Fitoterapia, 2014, 96: 103-108.
[8] Zhang M, Su P, Zhou YJ, et al. Identification of geranylgeranyl diphosphate synthase genes from tripterygium wilfordii[J]. Plant Cell Rep, 2015, 34(12): 2179-2188.
[9] Zhao YJ, Chen X, Zhang M, et al. Molecular cloning and characterisation of farnesyl pyrophosphate synthase from tripterygium wilfordii[J]. PLoS ONE, 2015, 10(5): e0125415.
[10] 任向楠, 梁琼麟. 基于质谱分析的代谢组学研究进展[J]. 分析测试学报, 2017, 36(2): 161-169.
[11] 葛纯, 曹蓓, 冯冬, 等. 药物代谢组学研究进展[J]. 药学进展, 2017, 41(4): 245-253.
[12] 孙玉萍, 苗蕾, 张蓓, 等. 尿酸与糖脂代谢指标的关联性及民族异质性研究[J]. 中国卫生检验杂志, 2014, 24(4): 595-598.
[13] 蒋晓颖, 金晶. 血清黄嘌呤氧化酶在代谢综合征患者中的意义[J]. 中国卫生检验杂志, 2013, 23(13): 2778-2780.
[14] 蒋武斌, 陈柏康, 孙良学. 上尿路结石与血脂代谢异常及炎症的关系研究[J]. 中国卫生检验杂志, 2017, 27(18): 2633-2635.
[15] 郭宾, 戴仁科. 代谢组学及其研究策略和分析方法进展[J]. 中国卫生检验杂志, 2007, 17(3): 554-563.
[16] 陈孟权, 周永列, 余细平, 等. 骨代谢标志物组合模型对诊断肺癌骨转移的价值[J]. 中国卫生检验杂志, 2016, 26(18): 2648-2651.
[17] 常立娟,李佐静,李清, 等.雷公藤致大鼠肾毒性血清代谢组学分析[J].中国实验方剂学杂志,2016,22(24):89-94.
[2] 李云鹃, 罗花, 黄丽贞, 等. 雷公藤的毒性机理及减毒方法研究进展[J]. 中华中医药杂志, 2017,32(6):2612-2614.
[3] 刘文成, 谭布珍, 方玉婷, 等. 植物雷公藤主要抗癌抗炎活性成分研究进展[J]. 中国临床药理学与治疗学, 2017, 22(3): 355-360.
[4] 陈一龙, 刘翔, 瞿显友, 等. 雷公藤属植物物种间的化学成分差异性研究[J]. 中国中药杂志, 2017, 42(2): 319-325.
[5] 郑海慧, 陈明毅, 钟丹敏, 等. 定量代谢组学研究进展[J]. 药学进展, 2017, 41(4): 254-262.
[6] 汪思媛, 赵星阳, 徐玮蔚, 等. 基于质谱技术的细胞代谢组学研究进展[J]. 中国细胞生物学学报, 2017, 39(8): 1130-1134.
[7] Wang C, Li CJ, Ma J, et al. Bioactive sesquiterpene polyol esters from the leaves of tripterygium wilfordii[J]. Fitoterapia, 2014, 96: 103-108.
[8] Zhang M, Su P, Zhou YJ, et al. Identification of geranylgeranyl diphosphate synthase genes from tripterygium wilfordii[J]. Plant Cell Rep, 2015, 34(12): 2179-2188.
[9] Zhao YJ, Chen X, Zhang M, et al. Molecular cloning and characterisation of farnesyl pyrophosphate synthase from tripterygium wilfordii[J]. PLoS ONE, 2015, 10(5): e0125415.
[10] 任向楠, 梁琼麟. 基于质谱分析的代谢组学研究进展[J]. 分析测试学报, 2017, 36(2): 161-169.
[11] 葛纯, 曹蓓, 冯冬, 等. 药物代谢组学研究进展[J]. 药学进展, 2017, 41(4): 245-253.
[12] 孙玉萍, 苗蕾, 张蓓, 等. 尿酸与糖脂代谢指标的关联性及民族异质性研究[J]. 中国卫生检验杂志, 2014, 24(4): 595-598.
[13] 蒋晓颖, 金晶. 血清黄嘌呤氧化酶在代谢综合征患者中的意义[J]. 中国卫生检验杂志, 2013, 23(13): 2778-2780.
[14] 蒋武斌, 陈柏康, 孙良学. 上尿路结石与血脂代谢异常及炎症的关系研究[J]. 中国卫生检验杂志, 2017, 27(18): 2633-2635.
[15] 郭宾, 戴仁科. 代谢组学及其研究策略和分析方法进展[J]. 中国卫生检验杂志, 2007, 17(3): 554-563.
[16] 陈孟权, 周永列, 余细平, 等. 骨代谢标志物组合模型对诊断肺癌骨转移的价值[J]. 中国卫生检验杂志, 2016, 26(18): 2648-2651.
[17] 常立娟,李佐静,李清, 等.雷公藤致大鼠肾毒性血清代谢组学分析[J].中国实验方剂学杂志,2016,22(24):89-94.