Li Pei, Liao Shan-Ting, Wang Jun-Song, Zhang Qian, Xu Ding-Qiao, Lv Yan, Yang Ming-Hua, Kong Ling-Yi
State Key Laboratory of Natural Medicines Department of Natural Medicinal Chemistry China Pharmaceutical University Nanjing China.
Center for Molecular Metabolism Nanjing University of Science and Technology China.
FEBS Open Bio. 2017 Jan 11;7(2):221-236. doi: 10.1002/2211-5463.12178. eCollection 2017 Feb.
Sepsis, characterized by systemic inflammation, often leads to end-organ dysfunction, such as acute kidney injury (AKI). Despite of the severity and frequency of septic AKI in clinic, its pathogenesis is still poorly understood. Combined with histopathology evaluations, mortality assessments, biochemical evaluations, reverse transcription (RT) reaction and quantitative real-time PCR, and western blot, H NMR-based metabolomics approach was applied to investigate effects of Huang-Lian-Jie-Du-Decotion (HLJDD), a traditional Chinese medicine prescription, and its four component herbs on lipopolysaccharide (LPS)-induced septic AKI and the underlying mechanism. LPS induced kidney dysfunction via activation of NF-κB and mitogen-activated protein kinases (MAPKs), by excessive production of IL-6, tumor necrosis factor-α, inducible nitric oxide synthase, and COX-2, producing perturbance in energy metabolism and oxidative stress. HLJDD and its component herbs could effectively inhibit LPS-induced AKI in mice by inhibiting NF-κB and MAPK activation and activating the Akt/HO-1 pathway, and by markedly ameliorating disturbances in oxidative stress and energy metabolism induced by LPS. The four-component herbs could complement each other.
脓毒症以全身炎症为特征,常导致终末器官功能障碍,如急性肾损伤(AKI)。尽管临床上脓毒症相关性急性肾损伤的严重性和发生率很高,但其发病机制仍未完全明确。结合组织病理学评估、死亡率评估、生化评估、逆转录(RT)反应、定量实时聚合酶链反应(qRT-PCR)、蛋白质免疫印迹法,采用基于核磁共振氢谱(1H NMR)的代谢组学方法,研究中药方剂黄连解毒汤(HLJDD)及其四味组成药材对脂多糖(LPS)诱导的脓毒症相关性急性肾损伤的影响及其潜在机制。LPS通过激活核因子κB(NF-κB)和丝裂原活化蛋白激酶(MAPKs),过度产生白细胞介素-6(IL-6)、肿瘤坏死因子-α(TNF-α)、诱导型一氧化氮合酶(iNOS)和环氧化酶-2(COX-2),导致能量代谢紊乱和氧化应激,从而诱导肾功能障碍。HLJDD及其组成药材可通过抑制NF-κB和MAPK的激活、激活Akt/血红素加氧酶-1(HO-1)信号通路,并显著改善LPS诱导的氧化应激和能量代谢紊乱,有效抑制小鼠LPS诱导的急性肾损伤。四味组成药材之间具有协同作用。