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定量巴豆酰化组分析揭示参芪注射液治疗糖尿病肾病的机制

Quantitative Crotonylome Analysis Reveals the Mechanism of Shenkang Injection on Diabetic Nephropathy.

作者信息

Wang Min, Zhang Bin, Zhang Chenyang, Zhang Xuelian, Tang Shuang, Sun Guibo, Sun Xiaobo

机构信息

Beijing Key Laboratory of Innovative Drug Discovery of Traditional Chinese Medicine (Natural Medicine) and Translational Medicine, Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100193, China.

Key Laboratory of New Drug Discovery Based on Classic Chinese Medicine Prescription, Chinese Academy of Medical Sciences, Beijing 100193, China.

出版信息

Oxid Med Cell Longev. 2022 Jul 12;2022:7767431. doi: 10.1155/2022/7767431. eCollection 2022.

DOI:10.1155/2022/7767431
PMID:39282151
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11401665/
Abstract

Shenkang injection (SKI) has been widely used in the clinical treatment of chronic kidney diseases in China because of its efficacy and safety. However, the underlying mechanism of SKI in diabetic nephropathy (DN) remains unclear. The present study aimed to investigate the renoprotective effects and possible mechanisms of SKI in diabetic db/db mice. We showed that SKI ameliorated hyperglycemia and abnormal renal biochemical parameters in db/db mice. Crotonylome and subsequent bioinformatics analyses indicated that the molecular functions of the significantly different crotonylated proteins regulated by SKI were closely related to oxidoreductase activity and oxidative phosphorylation might be one of the main pathways through which SKI functions in DN. Subsequent PRM validation of the selected crotonylated proteins confirmed these findings. In addition, we determined that SKI could regulate the expression of specific proteins in oxidative phosphorylation complexes and enhance antioxidant capacity. Taken together, our data suggest that SKI exerted the protective effect against DN potentially through reversing the abnormal crotonylation expression of oxidoreductase-related proteins.

摘要

参芎注射液（SKI）因其有效性和安全性，在中国已广泛应用于慢性肾脏病的临床治疗。然而，参芎注射液在糖尿病肾病（DN）中的潜在作用机制仍不清楚。本研究旨在探讨参芎注射液对糖尿病db/db小鼠的肾脏保护作用及其可能机制。我们发现参芎注射液改善了db/db小鼠的高血糖和异常肾脏生化指标。巴豆酰化蛋白质组及后续生物信息学分析表明，参芎注射液调控的显著差异巴豆酰化蛋白的分子功能与氧化还原酶活性密切相关，氧化磷酸化可能是参芎注射液在糖尿病肾病中发挥作用的主要途径之一。随后对所选巴豆酰化蛋白进行的PRM验证证实了这些发现。此外，我们还确定参芎注射液可以调节氧化磷酸化复合物中特定蛋白的表达，并增强抗氧化能力。综上所述，我们的数据表明参芎注射液可能通过逆转氧化还原酶相关蛋白的异常巴豆酰化表达，对糖尿病肾病发挥保护作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ff12/11401665/36fad24f1265/OMCL2022-7767431.007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ff12/11401665/76143263ead5/OMCL2022-7767431.001.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ff12/11401665/76143263ead5/OMCL2022-7767431.001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ff12/11401665/6467d8d43797/OMCL2022-7767431.002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ff12/11401665/b043c7ebbfe9/OMCL2022-7767431.003.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ff12/11401665/36fad24f1265/OMCL2022-7767431.007.jpg

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本文引用的文献

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Chin Herb Med. 2020 Jun 10;12(3):289-296. doi: 10.1016/j.chmed.2020.05.004. eCollection 2020 Jul.
2
Calenduloside E suppresses calcium overload by promoting the interaction between L-type calcium channels and Bcl2-associated athanogene 3 to alleviate myocardial ischemia/reperfusion injury.芍药苷 E 通过促进 L 型钙通道与 Bcl2 相关抗凋亡基因 3 的相互作用来抑制钙超载，从而减轻心肌缺血/再灌注损伤。
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Comprehensive analysis of lysine crotonylation modification in patients with chronic renal failure.慢性肾衰竭患者赖氨酸丁酰化修饰的综合分析。
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Phosphoproteomics reveals NMDA receptor-mediated excitotoxicity as a key signaling pathway in the toxicity of gelsenicine.磷酸化蛋白质组学揭示 NMDA 受体介导的兴奋性毒性是高乌甲素毒性的关键信号通路。
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