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绞股蓝皂苷通过抑制ERK信号通路减轻小鼠肾缺血/再灌注损伤。

Gypenoside attenuates renal ischemia/reperfusion injury in mice by inhibition of ERK signaling.

作者信息

Ye Qifa, Zhu Y I, Ye Shaojun, Liu Hong, She Xingguo, Niu Ying, Ming Yingzi

机构信息

Center of Transplant Medicine Engineering and Technology of Ministry of Health of The People's Republic of China, The Third Xiangya Hospital, Central South University, Changsha, Hunan 410013, P.R. China.

出版信息

Exp Ther Med. 2016 Apr;11(4):1499-1505. doi: 10.3892/etm.2016.3034. Epub 2016 Jan 29.

Abstract

is a traditional Chinese medicine reported to possess a wide range of health benefits. As the major component of , gypenoside (GP) displays various anti-inflammatory and anti-oxidant properties. However, it is unclear whether GP can protect against ischemia/reperfusion (I/R)-induced renal injury, and the underlying molecular mechanisms associated with this process remain unknown. In the present study, a renal I/R injury model in C57BL/6 mice was established. It was observed that, following I/R, serum concentrations of creatinine (Cr) and blood urea nitrogen (BUN) were significantly increased (P<0.01), indicating renal injury. Pretreatment with GP (50 mg/kg) significantly inhibited I/R-induced upregulation of serum Cr and BUN (P<0.01). Furthermore, renal malondialdehyde levels were significantly reduced in the I/R+GP group, compared with the I/R group (P<0.01), whereas renal tissue superoxide dismutase activity was significantly higher in the I/R+GP group compared with the I/R group (P<0.01). Further investigation demonstrated that pretreatment with GP produced inhibitory effects on the I/R-induced production of pro-inflammatory cytokines, including interleukin (IL)-1β, IL-6, tumor necrosis factor-α and interferon-γ (P<0.01). In addition, heme oxygenase 1 (HO-1) expression levels were significantly increased in the I/R group compared with the control (P<0.01), indicating the presence of oxidative damage. However, the I/R-induced upregulation of HO-1 was significantly attenuated by pretreatment with GP (P<0.01), which also suppressed I/R-induced apoptosis by inhibiting pro-apoptotic Bax and upregulating anti-apoptotic Bcl-2 in renal cells (P<0.01). Finally, the activity of ERK signaling was significantly increased in the I/R+GP group compared with the I/R group (P<0.05), which may be associated with the protective effect of GP against I/R-induced renal cell apoptosis. To conclude, the present results suggest that GP produces a protective effect against I/R-induced renal injury as a result of its anti-inflammatory and anti-apoptotic properties.

摘要

据报道,[具体中药名称未给出]是一种具有多种健康益处的传统中药。作为[具体中药名称未给出]的主要成分,绞股蓝总皂苷(GP)具有多种抗炎和抗氧化特性。然而,尚不清楚GP是否能预防缺血/再灌注(I/R)诱导的肾损伤,且与此过程相关的潜在分子机制仍不清楚。在本研究中,建立了C57BL/6小鼠肾I/R损伤模型。观察到,I/R后,血清肌酐(Cr)和血尿素氮(BUN)浓度显著升高(P<0.01),表明肾损伤。GP(50mg/kg)预处理显著抑制了I/R诱导的血清Cr和BUN上调(P<0.01)。此外,与I/R组相比,I/R+GP组肾丙二醛水平显著降低(P<0.01),而I/R+GP组肾组织超氧化物歧化酶活性显著高于I/R组(P<0.01)。进一步研究表明,GP预处理对I/R诱导的促炎细胞因子产生有抑制作用,包括白细胞介素(IL)-1β、IL-6、肿瘤坏死因子-α和干扰素-γ(P<0.01)。此外,与对照组相比,I/R组血红素加氧酶1(HO-1)表达水平显著升高(P<0.01),表明存在氧化损伤。然而,GP预处理显著减弱了I/R诱导的HO-1上调(P<0.01),其还通过抑制肾细胞中促凋亡的Bax并上调抗凋亡的Bcl-2来抑制I/R诱导的细胞凋亡(P<0.01)。最后,与I/R组相比,I/R+GP组ERK信号活性显著增加(P<0.05),这可能与GP对I/R诱导的肾细胞凋亡的保护作用有关。总之,目前的结果表明,GP因其抗炎和抗凋亡特性而对I/R诱导的肾损伤产生保护作用。

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