Study on the mechanism of Huoxue Tongluo Recipe improving diabetes retinopathy by inhibiting the focal death of retinal vascular endothelial cells mediated by VAV2-RAC1-NLRP3 signal pathway
活血通络方通过抑制VAV2-RAC1-NLRP3信号通路介导的视网膜血管内皮细胞焦亡改善糖尿病视网膜病变的机制研究

摘要

目的 探讨活血通络方（HXTLF）通过调控VAV2-RAC1-NLRP3信号通路抑制视网膜血管内皮细胞焦亡，改善糖尿病视网膜病变（DR）的作用及机制。方法 体内实验采用高脂高糖饮食联合链脲佐菌素（STZ）腹腔注射构建SD大鼠DR模型，随机分为对照组、模型组、HXTLF低（5 mL/kg/d）、中（10 mL/kg/d）、高（20 mL/kg/d）剂量组，连续灌胃干预3个月。观察各组VAV2-RAC1-NLRP3信号通路关键蛋白表达的影响。结果 HXTLF干预后，各剂量组（尤以中、高剂量组为著）能显著改善上述代谢紊乱与病理损伤。在机制层面，HXTLF有效降低了视网膜组织的氧化应激水平（降低MDA，提升SOD、GSH-Px活性）并抑制炎症因子IL-1β、TNF-α的释放。结论 活血通络方可能通过抑制VAV2-RAC1轴，进而阻断下游NLRP3炎症小体的活化与细胞焦亡进程。

Abstract

Objective To investigate the effect and mechanism of Huoxue Tongluo Recipe (HXTLF) on inhibiting retinal vascular endothelial cell pyroptosis by regulating VAV2-RAC1-NLRP3 signaling pathway, and improving diabetes retinopathy (DR).
Methods The in vivo experiment involved constructing a DR model in SD rats using a high-fat, high-sugar diet combined with intraperitoneal injection of streptozotocin (STZ). The rats were randomly divided into a control group, a model group, and low (5 mL/kg/day), medium (10 mL/kg/day), and high (20 mL/kg/day) dosage groups of HXTLF, with continuous gavage intervention for 3 months. The effects on the expression of key proteins in the VAV2-RAC1-NLRP3 signaling pathway were observed in each group.
Results After HXTLF intervention, each dose group (especially the medium and high dose groups) can significantly improve the metabolic disorders and pathological damage mentioned above. At the mechanistic level, HXTLF effectively reduces oxidative stress levels in retinal tissue (decreases MDA, increases SOD and GSH Px activity) and inhibits the release of inflammatory factors IL-1 β and TNF - α.
Conclusion   The Huoxue Tongluo Formula may inhibit the VAV2-RAC1 axis, thereby blocking the activation of downstream NLRP3 inflammasomes and the process of cell pyroptosis.