Department of Traditional Chinese Medicine, Qilu Hospital of Shandong University, Jinan, Shandong, 250012, PR China.
Shandong University of Traditional Chinese Medicine, Jinan, Shandong, 250355, PR China.
Eur J Pharmacol. 2020 Jun 5;876:173052. doi: 10.1016/j.ejphar.2020.173052. Epub 2020 Mar 2.
As diabetic macroangiopathy is becoming increasingly prevalent, it is urgent to explore preventive and therapeutic drugs and study the mechanism. Diabetic mice were induced by intraperitoneal injection of streptozotocin (STZ)for five consecutive days. Diabetic mice were divided into diabetic and allicin groups. After sacrifice, frozen aortic root sections were immunohistochemically stained for nuclear factor erythroid 2-related factor 2 (Nrf2) and inflammation cytokine-tumor necrosis factor α (TNF-α), and the remaining aortic tissues were analyzed by Western blot for the expression of proinflammation genes. In vitro, Nrf2 and inflammatory relative protein expression levels in Human Umbilical Vein Endothelial Cells (HUVECs) were examined. HUVECs proliferation and apoptosis were measured. TNF-α expression was increased in diabetic group compared to that in control group; this effect was alleviated in allicin-treated mice. Inflammation relative protein expression of Vascular Cell Adhesion Molecule 1(VCAM-1), Matrix metalloproteinase 2 (MMP-2), Inducible Nitric Oxide Synthase (iNOS), and monocyte chemotactic protein 1 (MCP-1) was higher in the diabetic group than in the control group; however, allicin treatment inhibited these diabetes-induced increase. In vitro, allicin treatment reversed the hyperglycemia-induced reduction in proliferation, and decreased the apoptosis induced by high glucose. Inflammation relative protein expression was consistent with that in vivo. Additionally, the expression of nuclear factor kappa-B (NF-κB)and Nrf2 was increased in both DM mice and HUVECs; allicin treatment induced a significant reduction in NF-κB level and improvement in Nrf2 level. Allicin alleviates inflammation caused by diabetic macroangiopathy, and the mechanism may occur via increasing Nrf2 and decreasing NF-κB.
随着糖尿病大血管病变的日益流行，迫切需要探索预防和治疗药物，并研究其机制。通过连续 5 天腹腔注射链脲佐菌素（STZ）诱导糖尿病小鼠。将糖尿病小鼠分为糖尿病组和大蒜素组。处死动物后，采用免疫组织化学法对核因子红细胞 2 相关因子 2（Nrf2）和炎症细胞因子肿瘤坏死因子-α（TNF-α）进行染色，对剩余的主动脉组织进行 Western blot 分析，检测促炎基因的表达。体外检测人脐静脉内皮细胞（HUVEC）中 Nrf2 和炎症相关蛋白的表达水平。检测 HUVEC 增殖和凋亡。与对照组相比，糖尿病组 TNF-α表达增加，大蒜素治疗组小鼠 TNF-α表达减轻。与对照组相比，糖尿病组血管细胞黏附分子 1（VCAM-1）、基质金属蛋白酶 2（MMP-2）、诱导型一氧化氮合酶（iNOS）和单核细胞趋化蛋白 1（MCP-1）的炎症相关蛋白表达增加，而大蒜素治疗抑制了这些由糖尿病引起的增加。体外，大蒜素治疗可逆转高血糖诱导的增殖减少，并减少高糖诱导的凋亡。炎症相关蛋白的表达与体内一致。此外，DM 小鼠和 HUVECs 中核因子 kappa-B（NF-κB）和 Nrf2 的表达增加，大蒜素治疗可显著降低 NF-κB 水平，提高 Nrf2 水平。大蒜素减轻糖尿病大血管病变引起的炎症，其机制可能是通过增加 Nrf2 和减少 NF-κB 实现的。
