基于代谢组学的生脉注射液治疗脓毒症作用机制研究
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摘要
目的采用代谢组学技术探究生脉注射液治疗脓毒症多成分、多靶标、多通路的作用机制。方法采用国际公认的盲肠结扎穿孔法复制脓毒症动物模型,空白组和模型组大鼠腹腔注射0.9%氯化钠注射液0.2 ml、生脉注射液组大鼠注射生脉注射液0.2 ml(2 mg/kg·min)。在此基础上对大鼠尿液进行代谢组学研究。通过对高分辨质谱数据的全谱分析,获取脓毒症大鼠终端代谢产物的生物学信息,聚焦关键代谢酶或代谢通路,阐明生脉注射液对脓毒症的干预作用。结果尿液代谢轮廓显示空白组和模型组大鼠的代谢分布明显分离,生脉注射液组处于两组间,且与空白组距离较近。进一步通过聚焦影响代谢分布异常的小分子代谢产物,通过与人类代谢组数据库中收录的代谢物二级图谱比对鉴定代谢物,分别是脯氨酸、L-蛋氨酸、亮氨酸、亚精胺、牛磺酸。通过对通路富集分析发现脓毒症大鼠代谢主要涉及牛磺酸和亚牛磺酸代谢、精氨酸和脯氨酸代谢、β-丙氨酸代谢、谷胱甘肽代谢、半胱氨酸和蛋氨酸代谢。结论采用生脉注射液治疗脓毒症大鼠临床疗效显著,调节牛磺酸和亚牛磺酸代谢、精氨酸和脯氨酸代谢等可能是治疗脓毒症的关键机制。
Objective To explore the mechanism of Shengmai Injection(生脉注射液) in treating sepsis with multi-component, multi-target and multi-pathway by metabolomics. Methods The sepsis animal model was established by the internationally recognized CLP method of cecum ligation and perforation. Rats in blank group and model group were intraperitoneally injected with 0.9% saline 0.2 mL and rats in Shengmai Injection group were injected with Shengmai Injection 0.2 mL(2 mg/kg·min). On this basis, metabolomics study of rat urine was carried out. Through full spectrum analysis of high resolution mass spectrometry data, biological information of terminal metabolites in septic rats was obtained, and key metabolic enzymes or metabolic pathways were focused to clarify the intervention effect of Shengmai Injection on sepsis. Results The urine metabolic profile showed that the metabolic distribution of rats in blank group and model group was distinctly separated. The Shengmai Injection group was between the two groups and was close to the blank group, which proved that Shengmai Injection had a good therapeutic effect on septic rats. Further, the metabolites were identified by focusing on the small molecule metabolites with abnormal metabolic distribution and comparing with the secondary metabolites in the human metabolome database, namely proline, L-methionine, leucine, arginine and taurine. The pathway enrichment analysis showed that the metabolism of sepsis rats mainly involved in taurine and taurine metabolism, arginine and proline metabolism, β-alanine metabolism, glutathione metabolism, cysteine and methionine metabolism.Conclusion Shengmai Injection has significant therapeutic effect on septic rats. Regulation of taurine and taurine metabolism, arginine and proline metabolism may be the key mechanism in the treatment of sepsis.
Objective To explore the mechanism of Shengmai Injection(生脉注射液) in treating sepsis with multi-component, multi-target and multi-pathway by metabolomics. Methods The sepsis animal model was established by the internationally recognized CLP method of cecum ligation and perforation. Rats in blank group and model group were intraperitoneally injected with 0.9% saline 0.2 mL and rats in Shengmai Injection group were injected with Shengmai Injection 0.2 mL(2 mg/kg·min). On this basis, metabolomics study of rat urine was carried out. Through full spectrum analysis of high resolution mass spectrometry data, biological information of terminal metabolites in septic rats was obtained, and key metabolic enzymes or metabolic pathways were focused to clarify the intervention effect of Shengmai Injection on sepsis. Results The urine metabolic profile showed that the metabolic distribution of rats in blank group and model group was distinctly separated. The Shengmai Injection group was between the two groups and was close to the blank group, which proved that Shengmai Injection had a good therapeutic effect on septic rats. Further, the metabolites were identified by focusing on the small molecule metabolites with abnormal metabolic distribution and comparing with the secondary metabolites in the human metabolome database, namely proline, L-methionine, leucine, arginine and taurine. The pathway enrichment analysis showed that the metabolism of sepsis rats mainly involved in taurine and taurine metabolism, arginine and proline metabolism, β-alanine metabolism, glutathione metabolism, cysteine and methionine metabolism.Conclusion Shengmai Injection has significant therapeutic effect on septic rats. Regulation of taurine and taurine metabolism, arginine and proline metabolism may be the key mechanism in the treatment of sepsis.
引文
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[9]陈荣琳,曹枫,童华生,等.生脉注射液对脂多糖诱导大鼠炎症反应及血管内皮损伤的影响[J].临床急诊杂志,2016,17(8):621-624.
[10]Su L,Li H,Xie A,et al.Dynamic changes in amino acid concentration profiles in patients with sepsis[J].Plos One,2015,10(4):e0121933.
[11]Zimbler N,Campbell A.Sepsis,SIRS and MODS[J].Surgery,2004,22(4):73-76.
[2]Lu Y,Yang Y,He X,et al.Esmolol reduces apoptosis and inflammation in early sepsis rats with abdominal infection[J].Am JEmerg Med,2017,35(10):1480-1484.
[3]Jing LI,Zhen S.TCM Standardization Today[J].World Journal of Acupuncture-Moxibustion,2017,27(3):21-25.
[4]Cheng CW,Bian ZX,Wu TX.Systematic review of Chinese herbal medicine for functional constipation[J].World J Gastroenterol,2009,15(39):4886-4895.
[5]赵滋苗,陆军,丁月平,等.生脉注射液对脓毒性休克早期液体复苏血管外肺水及相关因素的影响[J].浙江医学,2013,35(9):767-769,778.
[6]黄道永,陈矛,林凯旋.生脉注射液治疗脓毒性休克的疗效观察与体会[J].吉林医学,2011,32(17):3436-3438.
[7]周敦荣,姜悦.大剂量生脉注射液治疗脓毒性休克临床分析[J].医学信息(上旬刊),2011,24(6):3389-3391.
[8]李书清,杨毅,邱海波,等.生脉注射液对脓毒性休克绵羊血流动力学及氧代谢的影响[J].中国中西医结合急救杂志,2008,15(1):48-50.
[9]陈荣琳,曹枫,童华生,等.生脉注射液对脂多糖诱导大鼠炎症反应及血管内皮损伤的影响[J].临床急诊杂志,2016,17(8):621-624.
[10]Su L,Li H,Xie A,et al.Dynamic changes in amino acid concentration profiles in patients with sepsis[J].Plos One,2015,10(4):e0121933.
[11]Zimbler N,Campbell A.Sepsis,SIRS and MODS[J].Surgery,2004,22(4):73-76.