Yi Shi-Jian, Wu Yang, Li Lan-Lan, Liang Qian-Kun, Xiao Yue
Department of General Surgery, Shenzhen University General Hospital, No.1098, Xueyuan Avenue, Nanshan District, Shenzhen, 518055 Guangdong Province People's Republic of China.
Department of Infection Control, Shenzhen Fuyong People's Hospital, Shenzhen, 518103 People's Republic of China.
J Inflamm (Lond). 2020 Aug 28;17:30. doi: 10.1186/s12950-020-00258-0. eCollection 2020.
Traumatic coagulopathy (TC) arises primarily from coagulation system failure to maintain adequate hemostasis after serious blood loss or trauma. Circulatory homeostasis restoration is the mainstay of the therapeutic approach to TC, but the effects are significantly inhibited by coagulopathy.
To identify the therapeutic effects and underlying mechanism of compound amino acid (CAA) combined with high-dosage of vitamin B6 (VB6) on TC.
Rabbit traumatic model and cellular model were used to evaluate the effect of CAA combined with high-dosage of VB6 in TC. Blood concentrations of AST and ALT were measured using the Vitros 250 device while blood APTT, PT and TT concentrations were measured using commercial diagnostics kits. Furthermore, qRT-PCR, ELISA and Western blotting were used to determine the expression of clotting factor (II, VII, IX, X and XI), inflammatory factors (TNF-α, IL-6 and IL-1β) and HMGB1/TLR4/NF-κB signaling-related proteins, respectively.
In the rabbit traumatic model, CAA combined with high-dosage of VB6 therapy inhibited the high expression of AST and ALT, but increased the expression of coagulation factors. Additionally, in both the rabbit trauma model and cellular injury model, CAA combined with high-dosage of VB6 inhibited the expression of inflammatory factors (IL-6, TNF-α and IL-1β) and proteins (HMGB1, TLR4 and p-p65) in HMGB1/TLR4/NF-κB pathway. Most importantly, over-expression of HMGB1 reversed the effect of CAA and VB6 in HUVECs and EA.hy926 cells injury model.
CAA combined with high-dosage of VB6 alleviated TC and inhibited the expression and secretion of inflammatory factors by inhibiting HMGB1-mediated TLR4/NF-κB pathway.
创伤性凝血病（TC）主要源于严重失血或创伤后凝血系统无法维持足够的止血功能。恢复循环稳态是TC治疗方法的主要手段，但凝血病会显著抑制其效果。
确定复合氨基酸（CAA）联合高剂量维生素B6（VB6）对TC的治疗作用及潜在机制。
采用兔创伤模型和细胞模型评估CAA联合高剂量VB6对TC的影响。使用Vitros 250设备测量血液中AST和ALT的浓度，同时使用商业诊断试剂盒测量血液中APTT、PT和TT的浓度。此外，分别采用qRT-PCR、ELISA和蛋白质印迹法测定凝血因子（II、VII、IX、X和XI）、炎症因子（TNF-α、IL-6和IL-1β）以及HMGB1/TLR4/NF-κB信号相关蛋白的表达。
在兔创伤模型中，CAA联合高剂量VB6治疗可抑制AST和ALT的高表达，但增加凝血因子的表达。此外，在兔创伤模型和细胞损伤模型中，CAA联合高剂量VB6均抑制HMGB1/TLR4/NF-κB途径中炎症因子（IL-6、TNF-α和IL-1β）及蛋白（HMGB1、TLR4和p-p65）的表达。最重要的是，HMGB1的过表达逆转了CAA和VB6在人脐静脉内皮细胞（HUVECs）和EA.hy926细胞损伤模型中的作用。
CAA联合高剂量VB6通过抑制HMGB1介导的TLR4/NF-κB途径减轻TC，并抑制炎症因子的表达和分泌。
