人參皂苷於小鼠馬兜鈴酸腎病變之蛋白質體分析

Proteomic Analysis of Aristolochic Acid-Induced Nephopathy in Mice with Ginsenoside Rg1 Treatment

Yu-Ping Huang ； Shih-Ming Chen ； Jen-Ai Lee

《國際創新發明大會》 2012 (2012/09) Pp. 319-321

https://doi.org/10.30079/CIISANNUAL.201209.0319

摘要

馬兜鈴酸（AA）存在於馬兜鈴科植物中，會導致馬兜鈴酸腎病變，而其病理機轉尚未明確。人參皂苷（GS Rg1）是從Panax ginseng C.A. Meyer所分離出來具有活性的成份之一，此成分具有抗氧化以及抗發炎的功用。由於GS Rg1治療腎病變的機轉尚未明瞭，在本實驗中利將腎臟組織利用螢光高效能液相層析串聯質譜法（FD-LC-MS/MS）分析GS Rg1於小鼠馬兜鈴酸之蛋白質體，以解明GS Rg1之治療機轉。實驗結果顯示，在給予GS Rg1治療組以及只有馬兜鈴酸誘導腎損傷組中，經由FD-LC-MS/MS鑑定出100個蛋白質具有表現差異。這些蛋白質主要的功能包含抗氧化、腫瘤抑制以及訊息傳遞等。有37個蛋白質表現量在GS Rg1組中有明顯上升，包含acyl-CoA synthetase,long-chain acyl-CoA dehydrogenase 等。並且有35個蛋白質在AA誘導腎損傷組中有明顯的上升，包含ATP synthase (H+ transport), cytochrome c oxidase等。在GS Rg1治療組中發現兩個蛋白質參與脂肪酸代謝（β-oxidation），這兩個蛋白質會增加脂肪酸代謝，並且降低馬兜鈴酸誘導的脂質毒性（Lipotoxicity）。因此，我們推測GS Rg1腎臟保護作用機轉包括有降低上皮間質轉換（EMT）、降低馬兜鈴酸誘導的脂質毒性、抑制細胞凋亡和腫瘤增生的功能。

並列摘要

Aristolochic acid (AA) causes aristolochic acid nephropathy (AAN) and its pathogenic mechanism is still unclear. Ginsenoside Rg1 (GS Rg1), an active component of ginseng could be used to against oxidative stress and inflammation. Due to the treatment mechanism of GS Rg1 remains to be elucidated, we used a proteomic analysis by which renal tissues were analyzed by a fluorogenic derivatization-liquid chromatography-tandem mass spectrometry (FD-LC-MS/MS) method to find the treatment mechanism of GS Rg1. The results showed that in GS Rg1 treatment group compared with AA only group, there were 100 proteins altered and identified by FD-LC-MS/MS. The main functions of identified proteins including antioxidant, tumor suppressor, electron transport chain and so on. Thirty-seven proteins significantly increased in GS Rg1 group including acyl-CoA synthetase, long-chain acyl-CoA dehydrogenase. On the other hand, 35 proteins significantly increased in AA treatment group including ATP synthase (H+ transport), cytochrome c oxidase. In conclusion, we suggest that downregulated epithelial-to-mesenchymal transition (EMT), detoxified lipotoxicity, suppressed apoptosis and suppressed tumor proliferation were the nephroprotective functions of GS Rg1.

並列關鍵字

Aristolochic acid ； Ginsenoside Rg1 ； fluorogenic derivatization-liquid chromatography-tandem mass spectrometry