College of Health Preservation and Rehabilitation, Key Laboratory of Acupuncture and Medicine Research of Ministry of Education, Nanjing University of Chinese Medicine, Nanjing 210023, China; Affiliated Hospital of Nanjing University of Chinese Medicine, 155 Hanzhong Road, QinHuai District, Nanjing 210029, China.
School of Rehabilitation Science, Nanjing Normal University of Special Education, Nanjing 210038, China.
Phytomedicine. 2022 Feb;96:153860. doi: 10.1016/j.phymed.2021.153860. Epub 2021 Nov 17.
The inflammatory state of diabetes promotes high platelet response and endothelial adhesion, which are the main risk factors for cardiovascular events. Tetramethylpyrazine (TMP) is an amide alkaloid isolated from the traditional Chinese medicine Rhizoma Ligustici Chuanxiong, which has been widely used in the clinical treatment of ischemic cardiovascular disease.
This study aimed to investigate whether TMP could alleviate diabetes-induced high platelet response and endothelial adhesion and the underlying mechanisms.
Type 2 diabetes mellitus (T2DM) rat model was established by high-fat feeding combined with low dose of streptozotocin. Rats in the TMP treatment group were administered with TMP (100 or 200 mg/kg) for 21 days. Cultured human umbilical vein endothelial cells (HUVECs) were stimulated with glucose (5.5 mM) to induce endothelial activation. The NOD-like receptor protein 3 (NLRP3) over- and low-expressing cell models were established via transfection of NLRP3 lentivirus plasmid into HUVECs. INF39 (25 mg/kg), a chemical inhibitor of NLRP3 inflammasome, was used to explore the role of NLRP3 in T2DM associated high platelet response and endothelial adhesion.
TMP effectively improved the prothrombotic phenotypes and inhibited the expression of vascular inflammatory factors and adhesion molecules in T2DM rats. TMP inhibited NLRP3 inflammasome and reduced the adhesion of HUVECs to platelets and monocytes in vitro. Over-expression of NLRP3 blocked the effect of TMP on HUVECs activation and adhesion, while TMP had no effect on NLRP3 low-expressing HUVECs. The NLRP3 inhibitor INF39 produced similar effects of TMP on diabetes-induced high platelet response, endothelial adhesion and vascular inflammation.
TMP ameliorates diabetes-induced high platelet response and endothelial adhesion via inhibiting NLRP3 inflammasome activation in T2DM rats, which provide a new basis for the clinical prevention and treatment of diabetes-associated cardiovascular events.
糖尿病的炎症状态促进血小板高反应和内皮细胞黏附，这是心血管事件的主要危险因素。川芎嗪（TMP）是一种从中药川芎中分离出来的酰胺生物碱，已广泛应用于缺血性心血管疾病的临床治疗。
本研究旨在探讨川芎嗪是否可以减轻糖尿病引起的血小板高反应和内皮细胞黏附，并探讨其潜在机制。
通过高脂喂养联合小剂量链脲佐菌素建立 2 型糖尿病（T2DM）大鼠模型。TMP 治疗组大鼠给予 TMP（100 或 200mg/kg）治疗 21 天。用葡萄糖（5.5mM）刺激培养的人脐静脉内皮细胞（HUVECs）诱导内皮细胞活化。通过转染 NLRP3 慢病毒质粒建立 NLRP3 过表达和低表达细胞模型。用 NLRP3 炎症小体的化学抑制剂 INF39（25mg/kg）来探讨 NLRP3 在 T2DM 相关血小板高反应和内皮黏附中的作用。
TMP 能有效改善 T2DM 大鼠的血栓前表型，抑制血管炎症因子和黏附分子的表达。TMP 抑制 NLRP3 炎症小体，减少 HUVECs 与血小板和单核细胞的黏附。过表达 NLRP3 阻断了 TMP 对 HUVECs 激活和黏附的作用，而 TMP 对 NLRP3 低表达的 HUVECs 无影响。NLRP3 抑制剂 INF39 对糖尿病引起的血小板高反应、内皮黏附和血管炎症产生了与 TMP 相似的作用。
TMP 通过抑制 T2DM 大鼠 NLRP3 炎症小体的激活，改善糖尿病引起的血小板高反应和内皮黏附，为糖尿病相关心血管事件的临床预防和治疗提供了新的依据。
