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采用超高效液相色谱-质谱联用技术对双黄连注射液致大鼠过敏反应进行代谢组学研究。

Metabonomics delineates allergic reactions induced by Shuang-huang-lian injection in rats using ultra performance liquid chromatography-mass spectrometry.

机构信息

Research Institute of Traditional Chinese Medicine, Heilongjiang University of Chinese Medicine, Harbin 150040, China.

First Clinical Medical College, Heilongjiang University of Chinese Medicine, Harbin 150040, China.

出版信息

Chin J Nat Med. 2018 Aug;16(8):628-640. doi: 10.1016/S1875-5364(18)30101-8.

Abstract

Shuang-huang-lian Injection (SHLI) is the first successfully developed drug from traditional Chinese medicine (TCM) powder for injection, since its use for the treatment of acute respiratory tract infection, pneumonia, influenza, etc. At the same time, its allergic reactions have also emerged, which limits clinical applications. However, few scholars pay attention to the mechanism of allergic reactions. In this present study, metabonomics technology was used to explore the changes in endogenous metabolites in urine of the rat model of SHLI induced allergic reaction; we and analyzed the metabolites, metabolic pathway, and the mechanism which were closely related to the allergic reactions. The levels of serum histamine and tryptase were examined and changes in histomorphology were also observed. Based on the UPLC-Q-TOF/MS metabonomics, we carried out the pattern recognition analysis, selected potential biomarkers associated with allergic reactions, and explored the pathological mechanism for SHLI induced allergic reaction, which laid the foundation for the safety research of SHLI. Our results showed that SHLI increased the levels of serum histamine and tryptase in rats with allergic reaction; we determined 15 biomarkers in rat allergic reaction model induced by SHLI and found multiple metabolic pathways involved, such as metabolism of linolenic acid, phenylalanine, amino acid, 2-oxo acid, and purine and other metabolic pathways.

摘要

双黄连注射液(SHLI)是从中药粉末中成功开发的第一种用于注射的药物,用于治疗急性呼吸道感染、肺炎、流感等疾病。同时,其也出现了过敏反应,限制了其临床应用。然而,很少有学者关注过敏反应的机制。在本研究中,采用代谢组学技术探讨了 SHLI 致过敏反应大鼠模型尿液内源性代谢物的变化;我们分析了与过敏反应密切相关的代谢物、代谢途径和机制。检测了血清组氨酸和胰蛋白酶的水平,并观察了组织形态学的变化。基于 UPLC-Q-TOF/MS 代谢组学,我们进行了模式识别分析,选择了与过敏反应相关的潜在生物标志物,并探讨了 SHLI 致过敏反应的病理机制,为 SHLI 的安全性研究奠定了基础。我们的结果表明,SHLI 增加了过敏反应大鼠血清组氨酸和胰蛋白酶的水平;我们在 SHLI 诱导的大鼠过敏反应模型中确定了 15 个生物标志物,并发现了多个涉及的代谢途径,如亚油酸、苯丙氨酸、氨基酸、2-酮酸和嘌呤等代谢途径。

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