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蛋白质组学分析揭示刺蒺藜对大鼠肥胖相关肾小球病的肾脏保护作用。

Proteomic Analysis Reveals the Renoprotective Effect of Tribulus terrestris against Obesity-Related Glomerulopathy in Rats.

作者信息

Jiang Yue-Hua, Jiang Ling-Yu, Wu Sai, Jiang Wen-Jun, Xie Lifang, Li Wei, Yang Chuan-Hua

机构信息

Central Laboratory, Affiliated Hospital of Shandong University of Traditional Chinese Medicine.

First Clinical Medical College, Shandong University of Traditional Chinese Medicine.

出版信息

Biol Pharm Bull. 2018 Sep 1;41(9):1430-1439. doi: 10.1248/bpb.b18-00304. Epub 2018 Jul 6.

Abstract

Tribulus terrestris L. (Zygophyllaceae) (TT) is usually used as a cardiotonic, diuretic, and aphrodisiac, as well as for herbal post-stroke rehabilitation in traditional Chinese medicine. However, little is known about the renoprotective effects of TT on obesity-related glomerulopathy (ORG). In this study, 340 monomeric compounds were identified from TT extracts obtained with ethyl acetate combined with 50% methanol. In vitro, IC of TT was 912.01 mg/L, and the appropriate concentration of TT against oxidized-low density lipoprotein (ox-LDL) induced human renal glomerular endothelial cells (HRGECs) was 4 mg/L. TT significantly increased the viability (63.2%) and migration (2.33-fold increase) of HRGECs. ORG model rats were induced by a chronic high-fat diet (45%) for 20 weeks and were then treated with TT extract (2.8 g/kg/d) for 8 weeks. Subsequently, the kidneys were removed and their differentially expressed protein profile was identified using two-dimensional electrophoresis coupled with matrix-assisted laser desorption/ionization-time of flight (MALDI-TOF)-TOF MS. Molecular categorization and functional analysis of bioinformatic annotation suggested that excessive energy metabolism, decreased response to stress and low immunity were the potential etiologies of ORG. After TT administration for 8 weeks, body weight, blood pressure, serum cystatin C and cholesterol were decreased. Additionally, TT significantly enhanced the resistance of rats to ORG, decreased energy consumption and the hemorrhagic tendency, and improved the response to acute phase reactants and immunity. In conclusion, TT may play a protective role against ORG in rats.

摘要

刺蒺藜(蒺藜科)通常用作强心剂、利尿剂和壮阳药,在传统中医中也用于中风后的草药康复治疗。然而,关于刺蒺藜对肥胖相关肾小球病(ORG)的肾脏保护作用知之甚少。在本研究中,从用乙酸乙酯与50%甲醇混合提取得到的刺蒺藜提取物中鉴定出340种单体化合物。在体外,刺蒺藜的半数抑制浓度为912.01mg/L,其针对氧化低密度脂蛋白(ox-LDL)诱导的人肾小球内皮细胞(HRGECs)的适宜浓度为4mg/L。刺蒺藜显著提高了HRGECs的活力(提高63.2%)和迁移能力(增加2.33倍)。通过给予慢性高脂饮食(45%)20周诱导建立ORG模型大鼠,然后用刺蒺藜提取物(2.8g/kg/d)治疗8周。随后,取出肾脏,使用二维电泳结合基质辅助激光解吸/电离飞行时间(MALDI-TOF)-TOF质谱鉴定其差异表达蛋白质谱。生物信息注释的分子分类和功能分析表明,能量代谢过度、应激反应降低和免疫力低下是ORG的潜在病因。给予刺蒺藜8周后,体重、血压、血清胱抑素C和胆固醇降低。此外,刺蒺藜显著增强了大鼠对ORG的抵抗力,降低了能量消耗和出血倾向,并改善了急性期反应物反应和免疫力。总之,刺蒺藜可能对大鼠的ORG起到保护作用。

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