Department of Emergency Surgery, Affiliated Hospital of Nantong University, Nantong, Jiangsu 226001, P.R. China.
Mol Med Rep. 2019 Apr;19(4):2906-2912. doi: 10.3892/mmr.2019.9893. Epub 2019 Jan 24.
Severe trauma can result in secondary multiple organ dysfunction syndrome (MODS) and death. Inflammation response and oxidative stress promote the occurrence and development of MODS. TNFAIP3‑interacting protein 2 (TNIP2), which can repress the activation of nuclear factor‑κB (NF‑κB) and may be involved in MODS progression, has not been studied in regards to MODS. The present study aimed to investigate the expression, role and mechanism of TNIP2 in MODS following severe trauma. The expression level of TNIP2 was initially detected in the blood of patients with MODS using reverse transcription‑quantitative polymerase chain reaction and western blot assay. Then, to investigate the role of TNIP2 in MODS, a MODS rat model was conducted by trauma and the model rats were treated with TNIP2‑plasmid (intraperitoneal injection). Blood levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), lactate dehydrogenase (LDH), blood urea nitrogen (BUN), creatine (Cr) and creatine kinase (CK); and tumor necrosis factor α (TNF‑α), high‑mobility group box 1 (HMGB‑1), malondialdehyde (MDA) and total antioxidant capacity (TAC) in the different groups were assessed. In addition, activation of NF‑κB was assessed by detecting the level of phospho‑p65. The results showed that TNIP2 was significantly decreased in the blood of patients with MODS. TNIP2 was also significantly downregulated in the blood and the pulmonary, renal and hepatic tissues of MODS rats. The levels of ALT, AST, LDH, BUN, Cr and CK were markedly increased in the blood of MODS rats, and these increases were inhibited by TNIP2‑plasmid administration. Moreover, blood levels of TNF‑α, HMGB‑1 and MDA were significantly increased in MODS rats, while TAC was notably decreased, and these changes were prevented by TNIP2‑plasmid administration. Furthermore, it was found that activation of NF‑κB induced by MODS was eliminated by TNIP2‑plasmid. In conclusion, the data indicated that TNIP2 is significantly decreased in MODS following severe trauma, and it plays a protective role in MODS development by inhibiting the inflammation response and oxidative stress by preventing NF‑κB activation.
严重创伤可导致继发性多器官功能障碍综合征（MODS）和死亡。炎症反应和氧化应激促进 MODS 的发生和发展。TNFAIP3 相互作用蛋白 2（TNIP2）可抑制核因子-κB（NF-κB）的激活，可能与 MODS 的进展有关，但尚未对其在 MODS 中的作用进行研究。本研究旨在探讨 TNIP2 在严重创伤后 MODS 中的表达、作用及机制。采用逆转录-定量聚合酶链反应和 Western blot 检测 MODS 患者血液中 TNIP2 的表达水平。然后，通过创伤建立 MODS 大鼠模型，并采用 TNIP2-质粒（腹腔注射）处理模型大鼠，以探讨 TNIP2 在 MODS 中的作用。检测各组大鼠血液中丙氨酸氨基转移酶（ALT）、天门冬氨酸氨基转移酶（AST）、乳酸脱氢酶（LDH）、血尿素氮（BUN）、肌酐（Cr）和肌酸激酶（CK）以及肿瘤坏死因子-α（TNF-α）、高迁移率族蛋白 1（HMGB-1）、丙二醛（MDA）和总抗氧化能力（TAC）的水平。此外，通过检测磷酸化 p65 水平来评估 NF-κB 的激活情况。结果显示，MODS 患者血液中 TNIP2 显著降低。MODS 大鼠血液及肺、肾和肝组织中 TNIP2 也明显下调。MODS 大鼠血液中 ALT、AST、LDH、BUN、Cr 和 CK 水平明显升高，TNIP2-质粒给药可抑制这些升高。此外，MODS 大鼠血液中 TNF-α、HMGB-1 和 MDA 水平明显升高，TAC 明显降低，TNIP2-质粒给药可防止这些变化。此外，还发现 TNIP2-质粒可消除由 MODS 引起的 NF-κB 激活。综上所述，该数据表明，严重创伤后 MODS 中 TNIP2 显著降低，通过抑制 NF-κB 激活来抑制炎症反应和氧化应激，在 MODS 发展中发挥保护作用。
