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

Danshen injection ameliorates STZ-induced diabetic nephropathy in association with suppression of oxidative stress, pro-inflammatory factors and fibrosis
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DOI:
10.1016/j.intimp.2016.06.024
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发表时间:
2016-09-01
影响因子:
5.6
通讯作者:
Wang, Zheng
Wang, Zheng
中科院分区:
医学2区
文献类型:
--
作者:
Xu, Linhao;Shen, Peiqiang;Wang, Zheng

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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患者肾脏组织的保护作用。采用腹腔注射链脲佐菌素(STZ) (60 mg/kg)诱导大鼠糖尿病。对stz诱导的糖尿病大鼠按2种不同剂量(0.5或1 ml/kg/天)腹腔注射丹参液,持续6周。结果表明,stz诱导的糖尿病大鼠血清肌酐(sCr)和血尿素氮显著升高,丹参注射液可减轻这种升高。丹参注射液还可以改善肾小管和肾小球的肥大和扩张,可能是通过降低胶原和纤维连接蛋白的表达,从而抑制tgf - β 1/Smad通路。进一步研究发现,丹参注射液可提高stz诱导的糖尿病大鼠体内超氧化物歧化酶(SOD)活性,降低活性氧(ROS)和丙二醛(MDA)水平,从而抑制氧化应激。此外,我们还发现丹参注射液可抑制I κ B/ nf - κ B信号通路,降低糖尿病肾组织中肿瘤坏死因子- α (tnf - α)、白细胞介素-1 β (IL-1 β)、白细胞介素-6 (IL-6)等多种促炎因子的水平,提示炎症有抑制作用。总之,我们的研究结果表明,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。(C) 2016 Elsevier B.V.版权所有
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) (60 mg/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 1 ml/kg/day) for 6 weeks. 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-beta 1/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 I kappa B/NF-kappa B signaling pathway and reduce the level of a number of pro-inflammatory factors, including tumor necrosis factor-alpha (TNF-alpha), interleukin-1 beta (IL-1 beta) 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. (C) 2016 Elsevier B.V. All rights reserved.