基于代谢组学方法研究绿原酸对大鼠慢性肝脏损伤的保护作用
发布时间：2018-08-07 15:55
【摘要】：本实验目的是探究绿原酸对脂多糖诱导大鼠慢性肝脏损伤的保护作用。实验首先研究了膳食添加绿原酸对正常生理状态下大鼠血液和肝脏中内源性代谢物的影响。随后以长期低剂量的脂多糖应激建立大鼠慢性肝脏损伤模型，研究绿原酸对大鼠的生长性能、血液生化指标、肝脏指数、肝脏形态结构、肝脏抗氧化指标、肝脏能量代谢指标的影响，进一步采用核磁共振代谢组学的方法来研究绿原酸对慢性肝脏损伤大鼠血液和肝脏中内源性代谢物的影响。探讨绿原酸对大鼠慢性肝脏损伤的保护作用及其可能的机制。 结果表明：(1)绿原酸引起了正常生理状态下大鼠血液和肝脏中内源性代谢物的变化，与正常组相比，绿原酸显著增加了正常生理状态下大鼠血液中脂蛋白、甘氨酸和不饱和脂肪酸的含量(P0.05)，显著降低了β-羟基丁酸、乳酸、乙酰乙酸、丙酮酸、琥珀酸和柠檬酸的含量(P0.05)，显著增加了肝脏水溶性提取物谷胱甘肽的含量(P0.05)；(2)与脂多糖组相比，绿原酸显著降低了由脂多糖引起的大鼠末体重、平均日增重和食物转化率的升高(P＜0.05)；显著降低了大鼠血清中ALT和AST活性以及GLU和TG含量(P＜0.05)；显著升高肝脏组织中ALT和AST活性以及血液中TP的含量(P＜0.05)；HE染色显示，绿原酸能够明显改善慢性肝脏损伤大鼠的肝组织结构；显著升高大鼠肝脏组织中SOD活性(P＜0.05)，显著降低肝脏组织中MDA含量(P＜0.05)；显著升高大鼠肝脏组织中ATP的含量(P＜0.05)；(3)通过代谢组学的方法测定大鼠血清和肝脏内源性代谢物含量的变化，发现长期脂多糖应激抑制了大鼠机体的能量代谢，氨基酸代谢和谷胱甘肽代谢途径；绿原酸能够通过促进能量代谢，氨基酸代谢和谷胱甘肽代谢途径明显改善了脂多糖诱导的大鼠慢性肝脏损伤。 综上所述，绿原酸对脂多糖应激引起的大鼠慢性肝脏损伤具有一定的保护作用。甘氨酸和谷胱甘肽可能是绿原酸在机体内具有生物学活性的潜在生物标志物。绿原酸能够通过促进能量代谢，氨基酸代谢和谷胱甘肽代谢等途径，，明显改善了脂多糖诱导的大鼠机体脂质代谢紊乱、肝功能损伤、肝脏氧化损伤、肝脏线粒体损伤以及能量代谢障碍。
[Abstract]:The aim of this study was to investigate the protective effect of Lv Yuan acid on lipopolysaccharide induced chronic liver injury in rats. The effects of dietary supplementation of Lv Yuan acid on endogenous metabolites in blood and liver of rats under normal physiological conditions were studied. Then the chronic liver injury model of rats was established by long-term low dose lipopolysaccharide stress to study the growth performance, blood biochemical index, liver morphology, liver antioxidant index of Lv Yuan acid in rats. The effect of Lv Yuan acid on the endogenous metabolites in blood and liver of chronic liver injury rats was studied by nuclear magnetic resonance (NMR) method. To investigate the protective effect of Lv Yuan acid on chronic liver injury in rats and its possible mechanism. The results showed that: (1) Lv Yuan acid induced the changes of endogenous metabolites in blood and liver of rats under normal physiological condition. Compared with normal group, Lv Yuan acid significantly increased lipoprotein in blood of rats under normal physiological condition. The contents of glycine and unsaturated fatty acids (P0.05) significantly decreased the contents of 尾 -hydroxybutyric acid, lactic acid, acetoacetic acid, pyruvate, succinic acid and citric acid (P0.05), and significantly increased the content of glutathione (P0.05). (2) compared with lipopolysaccharide group, Lv Yuan acid significantly decreased the end weight, average daily gain and food conversion rate of rats induced by lipopolysaccharide (P < 0. 05), decreased the activities of ALT and AST, and the contents of GLU and TG in serum of rats (P < 0. 05). The activities of ALT and AST in liver tissue and the content of TP in blood were significantly increased (P < 0. 05). The results of HE staining showed that Lv Yuan acid could significantly improve the liver structure of chronic liver injury rats. The activity of SOD in rat liver tissue was significantly increased (P < 0. 05), the content of MDA in liver tissue was decreased (P < 0. 05), the content of ATP in rat liver tissue was significantly increased (P < 0. 05). (3) the changes of endogenous metabolites in serum and liver were determined by the method of metabolomics. It was found that long-term lipopolysaccharide stress inhibited the metabolism of energy, amino acid and glutathione in rats. Lv Yuan acid can improve the chronic liver injury induced by lipopolysaccharide in rats by promoting energy metabolism amino acid metabolism and glutathione metabolism pathway. In conclusion, Lv Yuan acid has a protective effect on chronic liver injury induced by lipopolysaccharide stress in rats. Glycine and glutathione may be potential biomarkers of Lv Yuan acids in vivo. Through promoting energy metabolism, amino acid metabolism and glutathione metabolism, Lv Yuan acid can significantly improve lipid metabolism disorder, liver function injury and liver oxidative damage induced by lipopolysaccharide in rats. Liver mitochondrial damage and energy metabolism disorders.
【学位授予单位】：南昌大学
【学位级别】：硕士
【学位授予年份】：2014
【分类号】：R965
本文编号：2170542
[Abstract]:The aim of this study was to investigate the protective effect of Lv Yuan acid on lipopolysaccharide induced chronic liver injury in rats. The effects of dietary supplementation of Lv Yuan acid on endogenous metabolites in blood and liver of rats under normal physiological conditions were studied. Then the chronic liver injury model of rats was established by long-term low dose lipopolysaccharide stress to study the growth performance, blood biochemical index, liver morphology, liver antioxidant index of Lv Yuan acid in rats. The effect of Lv Yuan acid on the endogenous metabolites in blood and liver of chronic liver injury rats was studied by nuclear magnetic resonance (NMR) method. To investigate the protective effect of Lv Yuan acid on chronic liver injury in rats and its possible mechanism. The results showed that: (1) Lv Yuan acid induced the changes of endogenous metabolites in blood and liver of rats under normal physiological condition. Compared with normal group, Lv Yuan acid significantly increased lipoprotein in blood of rats under normal physiological condition. The contents of glycine and unsaturated fatty acids (P0.05) significantly decreased the contents of 尾 -hydroxybutyric acid, lactic acid, acetoacetic acid, pyruvate, succinic acid and citric acid (P0.05), and significantly increased the content of glutathione (P0.05). (2) compared with lipopolysaccharide group, Lv Yuan acid significantly decreased the end weight, average daily gain and food conversion rate of rats induced by lipopolysaccharide (P < 0. 05), decreased the activities of ALT and AST, and the contents of GLU and TG in serum of rats (P < 0. 05). The activities of ALT and AST in liver tissue and the content of TP in blood were significantly increased (P < 0. 05). The results of HE staining showed that Lv Yuan acid could significantly improve the liver structure of chronic liver injury rats. The activity of SOD in rat liver tissue was significantly increased (P < 0. 05), the content of MDA in liver tissue was decreased (P < 0. 05), the content of ATP in rat liver tissue was significantly increased (P < 0. 05). (3) the changes of endogenous metabolites in serum and liver were determined by the method of metabolomics. It was found that long-term lipopolysaccharide stress inhibited the metabolism of energy, amino acid and glutathione in rats. Lv Yuan acid can improve the chronic liver injury induced by lipopolysaccharide in rats by promoting energy metabolism amino acid metabolism and glutathione metabolism pathway. In conclusion, Lv Yuan acid has a protective effect on chronic liver injury induced by lipopolysaccharide stress in rats. Glycine and glutathione may be potential biomarkers of Lv Yuan acids in vivo. Through promoting energy metabolism, amino acid metabolism and glutathione metabolism, Lv Yuan acid can significantly improve lipid metabolism disorder, liver function injury and liver oxidative damage induced by lipopolysaccharide in rats. Liver mitochondrial damage and energy metabolism disorders.
【学位授予单位】：南昌大学
【学位级别】：硕士
【学位授予年份】：2014
【分类号】：R965
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