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丹参注射液通过抑制氧化应激、促炎因子和纤维化改善链脲佐菌素诱导的糖尿病肾病。

Danshen injection ameliorates STZ-induced diabetic nephropathy in association with suppression of oxidative stress, pro-inflammatory factors and fibrosis.

作者信息

Xu Linhao, Shen Peiqiang, Bi Yanli, Chen Jian, Xiao Zhangang, Zhang Xiaoming, Wang Zheng

机构信息

Department of Anatomy, Faculty of Basic Medicine, Zhejiang Medical College, Hangzhou, Zhejiang 310053, PR China.

Research and Development Center of Chiatai Qingchunbao, Hangzhou, Zhejiang 310000, PR China.

出版信息

Int Immunopharmacol. 2016 Sep;38:385-94. doi: 10.1016/j.intimp.2016.06.024. Epub 2016 Jun 26.

DOI:10.1016/j.intimp.2016.06.024
PMID:27355131
Abstract

Diabetic nephropathy (DN) is one of the most frequent complications in diabetes mellitus. This study aimed to explore whether Danshen injection is protective to renal tissue in diabetes. Intraperitoneal injection of streptozotocin (STZ) (60mg/kg) was used to induce diabetes in rats. Some STZ-induced diabetic rats were also intraperitoneally injected with Danshen solution at two different dosages (0.5 or 1ml/kg/day) for 6weeks. Our results showed that serum creatinine (sCr) and blood urea nitrogen were significantly increased in STZ-induced diabetic rats, which was alleviated upon Danshen injection. Danshen injection was also found to ameliorate hypertrophy and dilatation of renal tubule and glomeruli possibly by decreasing the expression of collagen and fibronectin in association with suppression of TGF-β1/Smad pathway. Further investigation revealed that Danshen injection could increase the activity of superoxide dismutase (SOD), and reduce reactive oxygen species (ROS) and malondialdehyde (MDA) levels in STZ-induced diabetic rats, indicating suppression of oxidative stress. In addition, we also found that Danshen injection could suppress IκB/NF-κB signaling pathway and reduce the level of a number of pro-inflammatory factors, including tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β) and interleukin-6 (IL-6) in the diabetic renal tissue, indicating suppression of inflammation. In conclusion, our results demonstrated that Danshen injection may rescue STZ-induced diabetic nephropathy, possibly via suppressing the oxidative stress, inflammatory responses and fibrosis progression.

摘要

糖尿病肾病(DN)是糖尿病最常见的并发症之一。本研究旨在探讨丹参注射液对糖尿病大鼠肾组织是否具有保护作用。采用腹腔注射链脲佐菌素(STZ)(60mg/kg)诱导大鼠糖尿病。部分STZ诱导的糖尿病大鼠还分别以两种不同剂量(0.5或1ml/kg/天)腹腔注射丹参溶液,持续6周。我们的结果显示,STZ诱导的糖尿病大鼠血清肌酐(sCr)和血尿素氮显著升高,而丹参注射液注射后有所缓解。还发现丹参注射液可能通过降低胶原蛋白和纤连蛋白的表达并抑制TGF-β1/Smad信号通路,改善肾小管和肾小球的肥大及扩张。进一步研究表明,丹参注射液可提高STZ诱导的糖尿病大鼠超氧化物歧化酶(SOD)的活性,降低活性氧(ROS)和丙二醛(MDA)水平,提示其具有抑制氧化应激的作用。此外,我们还发现丹参注射液可抑制IκB/NF-κB信号通路,并降低糖尿病肾组织中多种促炎因子的水平,包括肿瘤坏死因子-α(TNF-α)、白细胞介素-1β(IL-1β)和白细胞介素-6(IL-6),提示其具有抑制炎症的作用。总之,我们的结果表明丹参注射液可能通过抑制氧化应激、炎症反应和纤维化进展来挽救STZ诱导的糖尿病肾病。

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