SIRT1 REPAIRS DEEP VEIN THROMBOSIS INDUCED BY OXIDATIVE STRESS THROUGH INHIBITING PRO-APOPTOTIC PATHWAY, INFLAMMATORY RESPONSE PATHWAY AND ACTIVATING ANTI-APOPTOTIC PATHWAY

Xing Che^{1, #, *}, Yang Zhan^{2, #}, Xiang Dai¹, Caiying Li¹, Yinghai Zhao¹ 

¹Department of Vascular Surgery, Taizhou People's Hospital, Taizhou 225300, PR China - ²Department of Critical Care Medicine, Taizhou People's Hospital, Taizhou 225300, PR China

Objective: To analyze the role of silencing information regulator-1 (SIRT1) in repairing oxidative stress-induced deep vein thrombosis by inhibiting the pro-apoptotic pathway and inflammatory response pathway and activating the anti-apoptotic pathway.

Methods: 72 healthy female C57BL/6 mice (clean grade) were randomly selected and divided into a sham operation group and model group, with 36 mice in each group. The deep vein thrombosis model was established, and the histopathological changes of inferior vena cava in mice were observed. The levels of malondialdehyde (MAD), superoxide dismutase (SOD), and the expression of SIRT1 in each group were measured. Human umbilical vein endothelial cells (HUVECs) were selected and cultured to determine the changes of cell activity and apoptosis in each group. The expression of apoptosis-related proteins in each group was measured. The expression of SIRT1, extracellular protein kinase (ERK), mitogen-activated protein kinase p38 (p38), nuclear transcription factor-κB (NF-κB), protein kinase B (Akt), glycogen synthesis kinase 3β (GSKβ), P-selection glycoprotein ligand 1 (PSGL-1), thrombomodulin (TM), von Willebrand factor (vWF), and tissue plasminogen activator (t-PA) was detected.

Results: In the sham operation group, the wall of inferior vena cava was regular and flat, the intima, muscularis, and tunica externa were intact, the endothelial cells were arranged regularly, the nuclei were normal, and there was no inflammatory cell infiltration and thrombosis. In the model group, the wall thickness of inferior vena cava was uneven, the volume of endothelial cells and the size of nuclei were different, inflammatory cell infiltration was observed, and a large amount of thrombosis was observed in the lumen. Compared with the sham operation group, SOD and SIRT expression levels in the inferior vena cava of the model group were significantly decreased, while MDA expression levels were obviously increased (P<0.01). Compared with the control group, the cell activity and expression levels of SIRT1 and Akt were remarkably decreased in the hydrogen peroxide group, and the apoptosis rate and expression levels of Bcl-2, Caspase-3, PSGL-1, TM, vWF, t-PA, ERK, p38, NF-κB, and GSK3β were obviously increased in the hydrogen peroxide group (P<0.05). Compared with the hydrogen peroxide group, the cell activity and the expression levels of SIRT1 and Akt were significantly increased in the SIRT1 group, and the apoptosis rate, the expression levels of Bcl-2, Caspase-3, PSGL-1, TM, vWF, t-PA, ERK, p38, NF-κB, and GSK3β were obviously decreased in the SIRT1 group (P<0.05).

Conclusion: SIRT1 was involved in the process of deep vein thrombosis by activating the PI3K/Akt/GSK3β signaling pathway and inhibiting the MAKs and NF-κB signaling pathways, suggesting that SIRT1 might repair oxidative stress-induced deep vein thrombosis by inhibiting the pro-apoptotic pathway and inflammatory response pathway and activating the anti-apoptotic pathway.