Gong Leilei, Hao Yangyang, Yin Xiaojie, Wang Lan, Ma Xiaojing, Cao Jun, Liang Rixin, Liao Fulong, Zhang Jianyong
Institute of Chinese Material Medical, China Academy of Chinese Medical Sciences Beijing 100700 China
Department of Chinese Material Medica, Capital Medical University Beijing 100067 China.
RSC Adv. 2018 Nov 6;8(65):37229-37242. doi: 10.1039/c8ra05548c. eCollection 2018 Nov 1.
: It has been recognized that exercise training can attenuate the progression of atherosclerosis (AS). The combined application of components from the fruit of Bge. Var. N.E. Br. (CP) and the root of Bge. (SM) has been effective in the prevention and treatment of atherosclerosis. The present work aims to investigate the joint effects of extracts from the fruit of CP and the root of SM with swimming on atherosclerosis in rats. : To establish a rat atherosclerosis model, a combined method of partial ligation of the left common carotid artery leading to low shear stress and a high-fat diet was employed. Blood samples were collected to detect the blood lipid profile, which included total cholesterol (T-CHO), low-density lipoprotein cholesterol (LDL-C), triglycerides (TG) and high-density lipoprotein cholesterol (HDL-C); endothelial cytokines such as 6-keto-prostaglandin F1α (PGF1α), endothelin (ET), thromboxane B (TXB), plasminogen activator inhibitor-1 (PAI-1), and von Willebrand factor (vWF); and inflammatory cytokines such as interleukin-1β (IL-1β), interleukin-6 (IL-6) and interleukin-10 (IL-10). Finally, the common carotid arteries of the rats were removed to observe pathological changes oil red O staining, and the gene expression of t-PA, PAI-1, and vWF was assayed real-time (RT) quantitative polymerase chain reaction (qPCR). : The joint effects of CPSM extract and swimming indicated significant interactions, including (1) decreased serum T-CHO, TG, and LDL-C; (2) decreased IL-6 and increased IL-10; (3) decreased TXB, PAI-1 and vWF; three-dimensional analysis showed that gene expression of PAI-1 was inhibited, vWF gene expression was downregulated, and COX-1 gene expression was increased; and (4) decreased lipoprotein retention in the carotid artery wall. : This research demonstrates that the combined therapy of CP and SM extracts with swimming can improve blood lipid levels and endothelial functions and attenuate the early signs of atherosclerosis in a rat model of atherosclerosis. The regulation of the gene expression of PAI, vWF and COX-1 may be the underlying cause of the effect. Methodologically speaking, three-dimensional surface plots of the joint effects of CPSM extract and swimming on parameters with quadratic fitting yielded a more accurate equation for describing the dose-response relationship in biomechanopharmacology. Such plots are likely worth using in pharmacology to quantify the effects induced by two medicinal factors.
人们已经认识到运动训练可以减缓动脉粥样硬化(AS)的进展。光果葶苈子(CP)果实成分与葶苈子(SM)根部成分联合应用在动脉粥样硬化的防治中已显示出效果。本研究旨在探讨CP果实提取物和SM根部提取物与游泳运动对大鼠动脉粥样硬化的联合作用。
为建立大鼠动脉粥样硬化模型,采用部分结扎左颈总动脉导致低剪切应力并结合高脂饮食的方法。采集血样检测血脂谱,包括总胆固醇(T-CHO)、低密度脂蛋白胆固醇(LDL-C)、甘油三酯(TG)和高密度脂蛋白胆固醇(HDL-C);内皮细胞因子,如6-酮-前列腺素F1α(PGF1α)、内皮素(ET)、血栓素B(TXB)、纤溶酶原激活物抑制剂-1(PAI-1)和血管性血友病因子(vWF);以及炎性细胞因子,如白细胞介素-1β(IL-1β)、白细胞介素-6(IL-6)和白细胞介素-10(IL-10)。最后,取出大鼠的颈总动脉观察病理变化(油红O染色),并通过实时(RT)定量聚合酶链反应(qPCR)检测t-PA、PAI-1和vWF的基因表达。
CP与SM提取物和游泳运动的联合作用显示出显著的相互作用,包括:(1)血清T-CHO、TG和LDL-C降低;(2)IL-6降低,IL-10升高;(3)TXB、PAI-1和vWF降低;三维分析显示PAI-1基因表达受到抑制,vWF基因表达下调,COX-1基因表达升高;以及(4)颈动脉壁中脂蛋白潴留减少。
本研究表明,CP和SM提取物与游泳运动的联合治疗可改善血脂水平和内皮功能,并减轻动脉粥样硬化大鼠模型中动脉粥样硬化的早期迹象。PAI、vWF和COX-1基因表达的调节可能是其作用的潜在原因。从方法学上讲,CP与SM提取物和游泳运动对参数的联合作用的三维表面图采用二次拟合得出了一个更准确的方程,用于描述生物力学药理学中的剂量反应关系。这种图可能在药理学中值得用于量化两种药物因素诱导的效应。