Chen Gao, Hong Chang, Hong-Bing Zhou, Qing Liu, Ying-Chun Bai, Quan-Li Liu, Wan-Fu Bai, Song-Li Shi
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引用次数: 1
摘要
为了揭示蒙古扁桃正丁醇提取物抗肾纤维化的作用机制,我们采用单侧输尿管梗阻(UUO)诱导大鼠肾纤维化,然后用蒙古扁桃正丁醇提取物(BUT)治疗。将60只雄性Sprague-Dawley大鼠随机分为假手术、肾纤维化(RF)模型、盐酸苯那普利治疗(1.5 mg kg-1)和but治疗(1.75、1.5和1.25 g kg-1)组,ig给药21 d。测定大鼠血清相关生化指标,观察组织病理形态。采用HPLC-Q-TOF-MS检测血清代谢组学。BUT降低了血尿素氮、血清肌酐和白蛋白水平,降低了组织中丙二醛和羟脯氨酸的含量。组织中超氧化物歧化酶的活性增加,观察到RF严重程度的改善。通过代谢组学分析鉴定了16个可能的生物标志物,并分析了6个关键代谢途径,包括TCA循环和酪氨酸代谢。经提取物处理后,在高、中、低剂量组分别可检测到8、12、9种可能的生物标志物。利用代谢组学鉴定的RF关键生物标志物受中剂量影响最大。蒙古包BUT提取物对大鼠RF有保护作用,应作为治疗该病的候选药物进行研究。
Metabolomics reveal the mechanism for anti-renal fibrosis effects of an n-butanol extract from Amygdalus mongolica.
To reveal the mechanism of anti-renal fibrosis effects of an n-butanol extract from Amygdalus mongolica, renal fibrosis was induced with unilateral ureteral obstruction (UUO) and then treated with an n-butanol extract (BUT) from Amygdalus mongolica (Rosaceae). Sixty male Sprague-Dawley rats were randomly divided into the sham-operated, renal fibrosis (RF) model, benazepril hydrochloride-treated model (1.5 mg kg-1) and BUT-treated (1.75, 1.5 and 1.25 g kg-1) groups and the respective drugs were administered intragastrically for 21 days. Related biochemical indices in rat serum were determined and histopathological morphology observed. Serum metabolomics was assessed with HPLC-Q-TOF-MS. The BUT reduced levels of blood urea nitrogen, serum creatinine and albumin and lowered the content of malondialdehyde and hydroxyproline in tissues. The activity of superoxide dismutase in tissues was increased and an improvement in the severity of RF was observed. Sixteen possible biomarkers were identified by metabolomic analysis and six key metabolic pathways, including the TCA cycle and tyrosine metabolism, were analyzed. After treatment with the extract, 8, 12 and 9 possible biomarkers could be detected in the high-, medium- and low-dose groups, respectively. Key biomarkers of RF, identified using metabolomics, were most affected by the medium dose. A. mongolica BUT extract displays a protective effect on RF in rats and should be investigated as a candidate drug for the treatment of the disease.
期刊介绍:
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