Department of Emergency, Ruijin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Department of General Surgery, Ruijin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Biochem Biophys Res Commun. 2018 Jun 22;501(2):358-364. doi: 10.1016/j.bbrc.2018.04.111.
To investigate the effect of intravenous Vitamin C (VC) on hemorrhagic shock (HS)-associated rat renal injury and the involved mechanism. Thirty SD rats were randomly assigned to the sham surgery (sham), hemorrhagic shock (HS), HS+100 mg/kg VC (H + VL), HS+500 mg/kg VC (H + VH) and HS+100 mg/kg VC + EX527 (H + VL + E) groups. Tissue and blood samples were collected 6 h after surgery. Kidney pathological changes were scored. Creatinine (CRE), blood urea nitrogen (BUN), tumor necrosis factor-α (TNF-α), and interleukin-1β (IL-1β) levels in serum and Vitamin C levels and superoxide dismutase (SOD) activity and the ability to suppress hydroxyl radical (RAFHR) in plasma were measured. The expression of Sirtuin1 (SIRT1), Acetyl-NF-κB (Ace-NF-κB), heme oxygenase-1 (HO-1), TNF-α, and IL-1β in tissues was analyzed by ELISA or western-blot. In the HS group, the kidney pathological score and CRE, BUN, TNF-α, and IL-1β levels in serum were significantly higher than in the Sham group (P < 0.05), while SOD and RAFHR were significantly decreased in the plasma (P < 0.05). SOD activity and SIRT1 expression were remarkably lower in the kidney in the HS group than in the Sham group (P < 0.05), while MDA, TNF-α, and IL-1β concentrations and Acetyl-NF-κB andHO-1 expression in the kidney showed a noteworthy increase compared to the Sham group (P < 0.05). Compared to the HS group, VC treatment led to a remarkable reduction in the kidney pathological score and CRE,BUN,TNF-α, and IL-1β levels (P < 0.05), and a significant increase in Vitamin C, SOD, and RAFHR levels in the plasma (P < 0.05). Additionally, MDA, TNF-α, IL-1β and Acetyl-NF-κB expression levels were decreased in the kidney (P < 0.05), while SOD, SIRT1 and HO-1 levels were notably enhanced. There were no differences between the H + VL and H + VH groups aside from plasma Vitamin C levels. The effect of Vitamin C was decreased after the addition of EX527, which inhibits SIRT1. Intravenous Vitamin C might attenuate HS-related renal injury via the SIRT1 pathway, and it appears that there were no differences in the effects between the high and low doses.
探讨静脉注射维生素 C（VC）对失血性休克（HS）相关大鼠肾损伤的影响及作用机制。
30 只 SD 大鼠随机分为假手术（sham）组、失血性休克（HS）组、HS+100mg/kg VC（H+VL）组、HS+500mg/kg VC（H+VH）组和 HS+100mg/kg VC+EX527（H+VL+E）组。术后 6h 采集组织和血液样本。对肾脏进行病理评分。检测血清中肌酐（CRE）、尿素氮（BUN）、肿瘤坏死因子-α（TNF-α）和白细胞介素-1β（IL-1β）水平，以及血浆中 VC 水平和超氧化物歧化酶（SOD）活性和羟自由基抑制能力（RAFHR）。采用 ELISA 或 Western blot 法分析组织中 Sirtuin1（SIRT1）、乙酰化 NF-κB（Ace-NF-κB）、血红素加氧酶-1（HO-1）、TNF-α和 IL-1β的表达。
与 sham 组相比，HS 组大鼠血清中肾脏病理评分和 CRE、BUN、TNF-α、IL-1β水平明显升高（P<0.05），而血浆中 SOD 和 RAFHR 水平明显降低（P<0.05）。HS 组大鼠肾脏 SOD 活性和 SIRT1 表达明显低于 sham 组（P<0.05），而 MDA、TNF-α和 IL-1β浓度以及肾脏中 Acetyl-NF-κB 和 HO-1 的表达明显高于 sham 组（P<0.05）。与 HS 组相比，VC 治疗后肾脏病理评分和 CRE、BUN、TNF-α和 IL-1β水平明显降低（P<0.05），血浆中 VC、SOD 和 RAFHR 水平明显升高（P<0.05）。此外，HS 组大鼠肾脏中 MDA、TNF-α、IL-1β和 Acetyl-NF-κB 的表达水平降低（P<0.05），而 SOD、SIRT1 和 HO-1 的表达水平明显升高。H+VL 组和 H+VH 组除血浆 VC 水平外，其他指标均无差异。加入抑制 SIRT1 的 EX527 后，VC 的作用减弱。
静脉注射 VC 可能通过 SIRT1 途径减轻 HS 相关的肾损伤，高、低剂量 VC 的作用无差异。
