Department of Oral & Maxillofacial Surgery, College of Stomatology, Guangxi Medical University, No.10 Shuangyong Road, Nanning, 530021, Guangxi, China.
Guangxi Key Laboratory of Oral and Maxillofacial Rehabilitation and Reconstruction, Nanning, 530021, Guangxi, China.
BMC Endocr Disord. 2021 Jan 26;21(1):19. doi: 10.1186/s12902-021-00682-0.
The present study aimed to evaluate the effect of artesunate (ART) on the reduction of cardiovascular complications in a type 1 diabetes model and to investigate the associated mechanism based on the receptor for advanced glycation end-product (RAGE)/NF-κB signaling pathway.
A total of 40 male Sprague-Dawley rats were randomly divided into five groups: The healthy, diabetic, 50 mg/kg ART (ig) treatment diabetic, 100 mg/kg ART (ig) treatment diabetic, and 6 U/kg insulin (iH) treatment diabetic groups. The treatment lasted 4 weeks after the diabetic model was established via intraperitoneal injection of streptozotocin. Blood samples were collected, and cardiovascular tissues were harvested and processed to measure various parameters after the animals were sacrificed. The myocardium and aortic arch tissues were evaluated using hematoxylin-eosin and Masson staining. Expression levels of RAGE, NF-κB, matrix metalloproteinase MMP9, MMP1 and CD68 in the myocardium and aortic arch tissues were detected using immunohistochemistry, and mRNA expression was determined using reverse transcription-quantitative PCR.
The results of the present study demonstrated that ART treatment may restrain diabetes-induced cardiovascular complications by maintaining heart and body weight while reducing blood glucose, as well as regulating blood lipid indicators to normal level (P < 0.05). The expression levels of NF-κB, CD68, MMP1, MMP9 and RAGE were decreased in the ART-treated diabetic rats (P < 0.05).
ART treatment may have a protective role against diabetes-associated cardiovascular complications in diabetic rats by inhibiting the expression of proteins in the RAGE/NF-κB signaling pathway and downstream inflammatory factors. High concentrations of ART had a hypoglycemic effect, while a low concentration of ART prevented cardiovascular complications.
本研究旨在评估青蒿琥酯（ART）对 1 型糖尿病模型中心血管并发症减少的影响，并基于晚期糖基化终产物受体（RAGE）/NF-κB 信号通路研究其相关机制。
将 40 只雄性 Sprague-Dawley 大鼠随机分为五组：健康组、糖尿病组、50mg/kg ART（ig）治疗糖尿病组、100mg/kg ART（ig）治疗糖尿病组和 6U/kg 胰岛素（iH）治疗糖尿病组。通过腹腔注射链脲佐菌素建立糖尿病模型后，进行 4 周的治疗。在动物处死时收集血液样本，并采集心血管组织进行处理，以测量各种参数。使用苏木精-伊红和 Masson 染色评估心肌和主动脉弓组织。使用免疫组织化学检测心肌和主动脉弓组织中 RAGE、NF-κB、基质金属蛋白酶 MMP9、MMP1 和 CD68 的表达水平，并使用逆转录定量 PCR 确定 mRNA 表达。
本研究结果表明，ART 治疗可能通过维持心脏和体重，降低血糖，以及将血脂指标调节至正常水平，从而抑制糖尿病引起的心血管并发症（P<0.05）。ART 治疗的糖尿病大鼠 NF-κB、CD68、MMP1、MMP9 和 RAGE 的表达水平降低（P<0.05）。
ART 治疗可能通过抑制 RAGE/NF-κB 信号通路和下游炎症因子中蛋白质的表达，对糖尿病大鼠的糖尿病相关心血管并发症具有保护作用。高浓度的 ART 具有降血糖作用，而低浓度的 ART 可预防心血管并发症。
