Qiu Runze, Long Jun, Zhou Liyu, Ma Yuanjing, Zhao Lingang, Liu Fumin, Yuan Dongping
School of Pharmacy, Jiangsu Key Laboratory for Pharmacology and Safety Evaluation of Chinese Materia Medica, Nanjing University of Chinese Medicine, Xianlin Dadao 138, Nanjing, 210023, China.
Jiangsu Province Hospital of TCM, Affiliated Hospital of Nanjing University of Traditional Chinese Medicine, Hanzhong Road 155, Nanjing, 210029, China.
Evid Based Complement Alternat Med. 2019 Jan 1;2019:2531979. doi: 10.1155/2019/2531979. eCollection 2019.
Atherosclerosis (AS) is a complicated arterial disease resulting from abnormal lipid deposition and inflammatory injury, which is attributed to Yin deficiency, accumulation of heat materials, and stasis of blood flow in Traditional Chinese Medicine (TCM) theory. Thus, according to TCM theory, the method of nourishing Yin (Yangyin), clearing away heat (Qingre), and promoting blood circulation (Huoxue) is a reasonable strategy, which has achieved remarkable clinical efficacy in the treatment of AS, but the mechanisms remain to be known. In this study, we evaluated the effects of Yangyin Qingre Huoxue Prescription (YQHP) on AS in ApoE mice suffering from a high-fat diet and heat shock protein (HSP65) attack. YQHP regulated levels of blood lipids and inflammation-linked cytokines as well as Th17/Treg ratio in peripheral blood. Suppressed IL-6-p-STAT3 signaling and restored IL-2-p-STAT5 signaling in the presence of YQHP may partake in the regulation of Th17 and Treg differentiation. Moreover, YQHP modulated transcriptional levels of costimulator CD80 in aortas as well corresponding to the downregulation of GM-CSF in serum and CD3 expression in CD4 T cells, which might indicate the potential of YQHP to regulate antigen presenting cells. All these effects eventually promoted the improvement of atherosclerotic lesions. In addition, YQHP promoted less monocyte infiltration in the liver and lower levels of AST, ALT, and AKP production than simvastatin. Conclusively, lipid-regulating and anti-inflammatory functions mediated by YQHP with lower hepatotoxicity than simvastatin hindered the progression of HSP65 aggravated AS in ApoE mice, indicating the effectiveness of Yangyin Qingre Huoxue Method in the treatment of AS.
动脉粥样硬化(AS)是一种由脂质异常沉积和炎症损伤引起的复杂动脉疾病,在中医理论中,其病因归属于阴虚、热邪积聚和血流瘀滞。因此,根据中医理论,滋阴(养阴)、清热、活血的方法是一种合理的策略,在AS治疗中已取得显著临床疗效,但其机制尚不清楚。在本研究中,我们评估了养阴清热活血方(YQHP)对高脂饮食和热休克蛋白(HSP65)攻击的ApoE小鼠AS的影响。YQHP调节了外周血脂、炎症相关细胞因子水平以及Th17/Treg比值。YQHP存在时抑制IL-6-p-STAT3信号传导并恢复IL-2-p-STAT5信号传导可能参与了Th17和Treg分化的调节。此外,YQHP调节主动脉中协同刺激分子CD80的转录水平,并相应下调血清中GM-CSF和CD4 T细胞中CD3的表达,这可能表明YQHP具有调节抗原呈递细胞的潜力。所有这些作用最终促进了动脉粥样硬化病变的改善。此外,与辛伐他汀相比,YQHP促进肝脏中单核细胞浸润减少,AST、ALT和AKP产生水平降低。总之,YQHP介导的调脂和抗炎功能,且肝毒性低于辛伐他汀,阻碍了HSP65加重的ApoE小鼠AS的进展,表明养阴清热活血法治疗AS的有效性。