Liang Rulian, Zhao Qing, Jian Guihua, Cheng Dongsheng, Wang Niansong, Zhang Guangyuan, Wang Feng
Department of Nephrology, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, China.
Department of Cardiology, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, China.
Cell Physiol Biochem. 2018;46(6):2616-2623. doi: 10.1159/000489688. Epub 2018 May 7.
BACKGROUND/AIMS: Tanshinone IIA is a chemical compound extracted from Salvia miltiorrhiza Bunge, a perennial plant also known as red sage used in traditional Chinese medicine. Tanshinone IIA has been shown to protect against various organ injuries. In this study, we hypothesized that Tanshinone IIA could play an anti-oxidative role in contrast-induced nephropathy (CIN) through enhancing Nrf2/ARE activation.
To test whether Tanshinone IIA can attenuate CIN, oxidative stress, and apoptosis, we utilized two models: an in vivo Sprague-Dawley rat model of ioversol-induced CIN and an in vitro cell model of oxidative stress in which HK2 cells, a human renal tubular cell line, are treated with hydrogen peroxide (H2O2). Rats were randomly assigned to 4 groups (n = 6 per group): control group, ioversol group (ioversol-induced CIN), vehicle group (ioversol-induced CIN rats pretreated with vehicle), and Tanshinone IIA group (ioversol-induced CIN rats pretreated with 25mg/kg Tanshinone IIA). Renal functions, renal injuries and apoptosis were evaluated by using serum creatinine, histological scoring, and TUNEL staning respectively. Malondialdehyde, 8-hydroxy-2' -deoxyguanosine, and intracellular reactive oxygen species were used for oxidative stress assessment. Levels of Nrf2 and heme oxygenase-1 (HO-1) were measured in vivo and in vitro.
Tanshinone IIA attenuated renal tubular necrosis, apoptosis and oxidative stress in rats and oxidative stress in HK2 cells. Furthermore, Tanshinone IIA activated Nrf2, and up-regulated HO-1 expression in vivo and in vitro, resulting in a reduction in oxidative stress.
Tanshinone IIA may protect against CIN through enhancing Nrf2/ARE activation.
背景/目的：丹参酮IIA是从丹参中提取的一种化合物，丹参是一种多年生植物，在传统中药中也被称为红参。丹参酮IIA已被证明可预防各种器官损伤。在本研究中，我们假设丹参酮IIA可通过增强Nrf2/ARE激活在对比剂肾病（CIN）中发挥抗氧化作用。
为了测试丹参酮IIA是否能减轻CIN、氧化应激和细胞凋亡，我们使用了两种模型：体内碘海醇诱导的CIN的Sprague-Dawley大鼠模型和体外氧化应激细胞模型，其中人肾小管细胞系HK2细胞用过氧化氢（H2O2）处理。大鼠随机分为4组（每组n = 6）：对照组、碘海醇组（碘海醇诱导的CIN）、溶剂组（用溶剂预处理的碘海醇诱导的CIN大鼠）和丹参酮IIA组（用25mg/kg丹参酮IIA预处理的碘海醇诱导的CIN大鼠）。分别使用血清肌酐、组织学评分和TUNEL染色评估肾功能、肾损伤和细胞凋亡。使用丙二醛、8-羟基-2'-脱氧鸟苷和细胞内活性氧进行氧化应激评估。在体内和体外测量Nrf2和血红素加氧酶-1（HO-1）的水平。
丹参酮IIA减轻了大鼠肾小管坏死、细胞凋亡和氧化应激以及HK2细胞中的氧化应激。此外，丹参酮IIA在体内和体外激活了Nrf2，并上调了HO-1表达，从而降低了氧化应激。
丹参酮IIA可能通过增强Nrf2/ARE激活来预防CIN。
