Lee Eun Soo, Kim Hong Min, Kang Jeong Suk, Lee Eun Young, Yadav Dhananjay, Kwon Mi-Hye, Kim You Mi, Kim Hyeon Soo, Chung Choon Hee
Department of Internal Medicine, Yonsei University Wonju College of Medicine, 162 Ilsan-Dong, Wonju, Gangwon-Do 220-701, Republic of Korea.
Department of Internal Medicine, Soonchunhyang University Cheonan Hospital, Cheonan 330-721, Republic of Korea.
Nephrol Dial Transplant. 2016 Mar;31(3):391-400. doi: 10.1093/ndt/gfv377. Epub 2015 Nov 12.
Hyperglycemia-induced endoplasmic reticulum (ER) stress and oxidative stress could be causes of renal fibrosis in diabetes. Oleanolic acid (OA) naturally occurs in fruits and vegetables. It has anti-inflammatory, antihyperlipidemic and antioxidant effects. N-acetylcysteine (NAC) is a precursor of glutathione, which has a strong antioxidant effect in the body. In this study, we investigated the therapeutic effects of OA and NAC in diabetic nephropathy (DN).
Otsuka Long-Evans Tokushima Fatty rats were treated with OA (100 mg/kg/day) or NAC (300 mg/kg/day) for 20 weeks by oral gavage.
The OA or NAC administration increased blood insulin secretion and superoxide dismutase levels, and decreased triglycerides and urinary albumin/creatinine levels. In the kidney, the damaged renal structure recovered with OA or NAC administration, through an increase in nephrin and endothelial selective adhesion molecules and a decrease in transforming growth factor-β/p-smad2/3 and ER stress. Reactive oxygen species and ER stress were increased by high glucose and ER stress inducers in cultured mesangial cells, and these levels recovered with OA (5.0 μM) or NAC (2.5 mM) treatment.
The findings in this study suggest that OA and NAC have therapeutic effects for DN through an antioxidant effect and ER stress reduction.
高血糖诱导的内质网（ER）应激和氧化应激可能是糖尿病肾纤维化的病因。齐墩果酸（OA）天然存在于水果和蔬菜中。它具有抗炎、抗高血脂和抗氧化作用。N-乙酰半胱氨酸（NAC）是谷胱甘肽的前体，在体内具有强大的抗氧化作用。在本研究中，我们探讨了OA和NAC对糖尿病肾病（DN）的治疗作用。
通过口服灌胃给予大冢Long-Evans Tokushima Fatty大鼠OA（100 mg/kg/天）或NAC（300 mg/kg/天），持续20周。
给予OA或NAC可增加血液胰岛素分泌和超氧化物歧化酶水平，并降低甘油三酯和尿白蛋白/肌酐水平。在肾脏中，给予OA或NAC后，受损的肾脏结构得以恢复，这是通过增加nephrin和内皮选择性黏附分子以及降低转化生长因子-β/p-smad2/3和ER应激实现的。在培养的系膜细胞中，高糖和ER应激诱导剂可增加活性氧和ER应激，而OA（5.0 μM）或NAC（2.5 mM）处理可使这些水平恢复。
本研究结果表明，OA和NAC通过抗氧化作用和减轻ER应激对DN具有治疗作用。
