腺嘌呤所致大鼠肾损伤的蛋白质组变化及其白头翁皂苷B4的调节作用

doi:10.5246/jcps.2019.01.002

中国药学(英文版) ›› 2019, Vol. 28 ›› Issue (1): 10-20.DOI: 10.5246/jcps.2019.01.002

腺嘌呤所致大鼠肾损伤的蛋白质组变化及其白头翁皂苷B4的调节作用

何鹿玲^1,2#, 龚琴^1,2#, 余煊³, 王木兰¹, 翁莎莎¹, 雷帆³, 高红伟⁴, 罗颖颖^1,2, 冯育林^1,2, 杨世林^1,2, 李俊^1,2*, 杜力军^1,3*

1. 江西中医药大学创新药物与高效节能降耗制药设备国家重点实验室, 江西南昌 330006
2. 江西中医药大学, 江西南昌 330006
3. 清华大学生命科学学院, 北京 100084
4. 广西中医药大学药学院, 南宁 530000

收稿日期:2018-11-19 修回日期:2018-12-19 出版日期:2019-01-27 发布日期:2018-12-26
通讯作者: Tel.: +86-18070090101; +86-13810460205, E-mail: 21363492@qq.com; lijundu@mail.tsinghua.edu.cn
基金资助:
National Innovative Drugs 13th Five-Year Major Special Project of China (Grant No. 2018ZX09301030-002).

Proteomic changes in rat kidney injured by adenine and the regulation of anemoside B4

Luling He^1,2#, Qin Gong^1,2#, Xuan Yu³, Mulan Wang², Shasha Wong², Fan Lei³, Hongwei Gao⁴, Yingying Luo^1,2, Yulin Feng^1,2, Shilin Yang^1,2, Jun Li^1,2*, Lijun Du^2,3*

1. Jiangxi University of Traditional Chinese Medicine, Nanchang 330006, China
2. State Key Laboratory of Innovative Drugs and Efficient Energy-saving Pharmaceutical Equipment, Nanchang 330006, China
3. School of Life Sciences, Tsinghua University, Beijing 100084, China
4. College of Pharmacy, Guangxi University of Chinese Medicine, Nanning 530000, China

Received:2018-11-19 Revised:2018-12-19 Online:2019-01-27 Published:2018-12-26
Contact: Tel.: +86-18070090101; +86-13810460205, E-mail: 21363492@qq.com; lijundu@mail.tsinghua.edu.cn
Supported by:
National Innovative Drugs 13th Five-Year Major Special Project of China (Grant No. 2018ZX09301030-002).

摘要/Abstract

摘要：

腺嘌呤常常用于制作慢性肾损伤及其肾间质纤维化的动物模型。除了炎性损伤之外, 作为内源性物质的腺嘌呤对肾脏的损害尚未得到充分研究和阐明。为此, 我们利用LC-MS/MS技术对腺嘌呤负荷后大鼠肾脏的蛋白质组学进行了分析, 并观察了anemoside B4(B4)的作用。结果表明, 腺嘌呤与正常组相比可以下调285个基因, 上调大鼠肾组织中的164个基因。下调基因主要影响能量代谢的通路, 而上调基因则影响炎症反应途径和其它一些代谢途径。B4可以显著逆转下调基因中的40个基因, 这些基因涉及线粒体、氧化还原过程、细胞外外泌体、乙酰化和其他信号传导途径。同时, B4可明显抑制由腺嘌呤引起的6个上调基因, 主要涉及细胞周期、卵母细胞减数分裂、PI3K-Akt等信号通路。使用实时定量PCR方法对其中一些基因进行mRNA表达, 其结果也与蛋白质组学分析结果基本一致。因此可见, 由腺嘌呤引起的大鼠肾损伤更复杂, 不仅与炎症反应有关, 而且对身体各种代谢过程有广泛影响。该工作为全面了解腺嘌呤诱导的肾损伤提供了有价值的线索。

关键词: 腺嘌呤, 慢性肾损伤, 蛋白质组学, 白头翁皂苷B4, 大鼠

Abstract:

Adenine is commonly used to establish the animal models for chronic kidney injury and its renal interstitial fibrosis. As an endogenous substance, adenine-induced kidney damage has not yet been fully studied and elucidated, except for inflammatory reaction. Here we analyzed the proteomics of kidney of rats after adenine overloading using LS-MS/MS assay, and observed the role of anemoside B4 (B4). The results showed that adenine could down-regulate 285 proteins and up-regulate 164 proteins in rat kidney tissue compared with the normal group. Down-regulated proteins mainly affected related pathways, such as energy metabolism, while up-regulated proteins affected inflammatory response pathways and metabolic pathways. B4 could significantly reverse the down-regulation of about 40 proteins, which were involved in mitochondria, redox processes, extracellular exosomes, acetylation and other signaling pathways. Simultaneously, B4 could inhibit the up-regulation of five proteins caused by adenine, which were involved in cell cycle, oocyte meiosis, PI3K-Akt and other signaling pathways. Further experimental results of mRNA expression using real-time PCR assay supported the proteomic analysis. Therefore, we proposed that the damage of rat kidney caused by adenine was more complicated, not only with an inflammatory reaction, but also with extensive effects to various metabolic processes in the body. This work provided a valuable clue for comprehensive understanding of adenine-induced renal damage.

Key words: Adenine, Chronic kidney injury, Proteome, Anemoside B4, Rat

中图分类号:

R962

Supporting:

何鹿玲, 龚琴, 余煊, 王木兰, 翁莎莎, 雷帆, 高红伟, 罗颖颖, 冯育林, 杨世林, 李俊, 杜力军. 腺嘌呤所致大鼠肾损伤的蛋白质组变化及其白头翁皂苷B4的调节作用[J]. 中国药学(英文版), 2019, 28(1): 10-20.

Luling He, Qin Gong, Xuan Yu, Mulan Wang, Shasha Wong, Fan Lei, Hongwei Gao, Yingying Luo, Yulin Feng, Shilin Yang, Jun Li, Lijun Du. Proteomic changes in rat kidney injured by adenine and the regulation of anemoside B4[J]. Journal of Chinese Pharmaceutical Sciences, 2019, 28(1): 10-20.

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腺嘌呤所致大鼠肾损伤的蛋白质组变化及其白头翁皂苷B4的调节作用

Proteomic changes in rat kidney injured by adenine and the regulation of anemoside B4

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