基于SIRT1/NF-κB信号通路探讨丹酚酸A改善慢性肾病大鼠血管内皮损伤和炎症的调控机制

Chronic kidney disease (CKD), also known as chronic renal disease, is a gradual loss of kidney function over time. Now it has been a cosmopolitan public health problem. Many studies have demonstrated that CKD patients face increased risk of cardiovascular disease (CVD), which has a significant impact upon patient mortality. Therefore, the prevention and treatment of CVD has become the key to the management of patients with CKD. Endothelial dysfunction and vascular inflammation are the beginning of atherosclerosis (AS), which is the pathological basis of CVD. Anti-inflammation, improving endothelial cell is a new trend of inhibiting AS, and it will be the potential, significant research direction for CVD prevention and treatment. The dried root of Salvia miltiorrhiza Bunge (Danshen) is a popular traditional Chinese medicine and has been widely used in both Asian and Western countries for the treatment of various diseases including cerebrovascular diseases, coronary artery diseases, and myocardial infarction, hepatitis, hemorrhage, diabetes mellitus and menstrual abnormalities for thousands of years. Salvianolic acid A (SAA) is one water-solubility component of Danshen. In our earlier study, we have demonstrated that SAA exhibited its anti-inflammatory effect via the NF-κB pathway in LPS-stimulated HK-2 cells reduced production of inflammatory mediators. Our current study may reveal a new SAA effect that it could against aortic injury by anti-inflammation and improving endothelial cell in CKD rat and LPS-stimulated HUVECs. We would prove that SAA exhibites this effect via the SIRT1/NF-κB signaling by using gene transfection technology. This study would show a new effect of SAA, provide a new idea for CVD prevention and cure.

慢性肾脏病（CKD）是世界性的公共健康问题，而心血管疾病（CVD）是CKD病患者的主要死亡原因，对CKD患者的CVD进行干预治疗十分重要。血管内皮细胞损伤和炎症反应是CVD病理基础-动脉粥样硬化（AS）的开始，抑制炎症反应，改善内皮细胞损伤是抗AS领域研究的新发展趋势，是防治CVD最具潜力和研究意义的全新方向。中药丹参是治疗CVD的常用中药，前期研究发现其水溶性成分丹酚酸A能够显著降低细胞炎症模型中炎症因子的分泌及表达，具有明显的抗炎症效果。本课题拟建立CKD大鼠模型和内皮细胞炎症模型，明确丹酚酸A改善炎症反应、减轻内皮细胞损伤的血管保护作用机制，利用基因转染技术揭示丹酚酸A介导SIRT1/NF-κB信号通路抑制炎症过程。本课题的实施将对丹酚酸A用于血管保护及作用机制提供一个全新认识，为拓展丹酚酸A的临床适应症提供有意义的探索，为CVD的防治，提高CKD治疗效果提供新思路。

慢性肾脏病（CKD）是世界性的公共健康问题，而心血管疾病（CVD）是CKD病患者的主要循环系统并发症，具有高发病率和死亡率，对CKD患者的CVD进行干预治疗十分重要。血管内皮细胞损伤和炎症反应是CVD病理基础-动脉粥样硬化（AS）的开始，抑制炎症反应，改善内皮细胞损伤是抗AS领域研究的新发展趋势，是防治CVD最具潜力和研究意义的全新方向。中药丹参是治疗CVD的常用中药，前期研究发现其水溶性成分丹酚酸A能够显著降低细胞炎症模型中炎症因子的分泌及表达，具有明显的抗炎症效果。本项目通过建立5/6肾切除慢性肾病大鼠模型，观察了丹酚酸A的对其肾脏及血管的保护作用。实验结果明确丹酚酸A能够通过改善炎症反应、减轻内皮损伤的作用保护主动脉损伤；阐明了SIRT-1/ NF-κB通路的表达与慢性肾病引起的血管中内皮细胞损伤及炎症的关系；揭示了丹酚酸A通过激活SIRT1/NF-κB信号通路起到抗炎症反应。本项目的完成可作为丹酚酸A用于慢性疾病并发心血管的治疗提供充实的理论和实验基础，为阐明丹酚酸A对保护心血管作用及机制提供创新型的探索方向，为中药的现代化研究提供参考。