Deng Jing-Na, Li Quan, Sun Kai, Pan Chun-Shui, Li Huan, Fan Jing-Yu, Li Gao, Hu Bai-He, Chang Xin, Han Jing-Yan
Department of Integration of Chinese and Western Medicine, School of Basic Medical Sciences, Peking University, Beijing, China.
Tasly Microcirculation Research Center, Peking University Health Science Center, Beijing, China.
Front Physiol. 2019 Sep 10;10:1128. doi: 10.3389/fphys.2019.01128. eCollection 2019.
This study was to explore the protective effects of cardiotonic pills (CP) or/and recombinant human prourokinase (proUK)on the atherosclerosis and the potential underlying mechanism.
Atherosclerosis was induced in LDLR/ mice by high fat diet contained 20% lard and 0.5% cholesterol. Daily oral administration of CP (130 mg/kg) or/and intravenous injection of proUK (2.5 mg/kg, twice a week) began at 8 weeks after feeding with high fat diet and continued for 4 weeks. CP alone treatment markedly decreased plasma triglyceride, but did not ameliorate atherosclerosis plaque. No effect was observed for proUK alone on any endpoints tested. CP plus proUK induced a significantly reduction in the atherosclerotic lesions, along with decreased levels of total cholesterol, triglyceride in the plasma. CP plus proUK inhibited the elevated hepatic total cholesterol and triglyceride in high fat diet-fed LDLR mice, up-regulating the expressions of ATP-binding cassette gene 5 and 8, and adipose triglyceride lipase. In the aorta, CP plus proUK inhibited the expression of scavenger receptor A and CD36 in LDLR mice. In addition, we observed that systemic inflammation was inhibited, manifested downregulation of plasma macrophage inflammatory protein-1α and intercellular cell adhesion molecule-1.
CP plus proUK effectively attenuated atherosclerosis plaque in LDLR mice, which is associated with normalizing the lipid metabolism in the liver and aorta, reducing phagocytosis of receptor-mediated modified-LDL uptake and inhibiting systemic inflammation.
本研究旨在探讨强心丸（CP）或/和重组人尿激酶原（proUK）对动脉粥样硬化的保护作用及其潜在的作用机制。
通过含20%猪油和0.5%胆固醇的高脂饮食诱导低密度脂蛋白受体基因敲除（LDLR−/−）小鼠发生动脉粥样硬化。在高脂饮食喂养8周后开始每日口服CP（130 mg/kg）或/和静脉注射proUK（2.5 mg/kg，每周两次），持续4周。单独使用CP治疗可显著降低血浆甘油三酯水平，但并未改善动脉粥样硬化斑块。单独使用proUK对所检测的任何终点指标均无影响。CP加proUK可显著减少动脉粥样硬化病变，同时降低血浆总胆固醇、甘油三酯水平。CP加proUK可抑制高脂饮食喂养的LDLR−/−小鼠肝脏中总胆固醇和甘油三酯的升高，上调ATP结合盒基因5和8以及脂肪甘油三酯脂肪酶的表达。在主动脉中，CP加proUK可抑制LDLR−/−小鼠中清道夫受体A和CD36的表达。此外，我们观察到全身炎症受到抑制，表现为血浆巨噬细胞炎性蛋白-1α和细胞间黏附分子-1的下调。
CP加proUK可有效减轻LDLR−/−小鼠的动脉粥样硬化斑块，这与肝脏和主动脉脂质代谢正常化、减少受体介导的修饰低密度脂蛋白摄取的吞噬作用以及抑制全身炎症有关。
