Zhang Yi-Guan, Zhang Hai-Gang, Zhang Guo-Yuan, Fan Ji-Shan, Li Xiao-Hui, Liu Yan-Hua, Li Shu-Hui, Lian Xue-Mei, Tang Zhong
Institute of Materia Medica and Department of Pharmaceutics, College of Pharmacy, Third Military Medical University, Chengdu, China.
Clin Exp Pharmacol Physiol. 2008 Oct;35(10):1238-44. doi: 10.1111/j.1440-1681.2008.04997.x. Epub 2008 Jul 9.
Previous studies have reported on the anti-atherosclerotic effects of Panax notoginseng saponins (PNS). The aim of the present study was to explore the molecular mechanisms responsible for the anti-atherosclerotic effects of PNS and the inflammatory response. Thirty rats were randomly divided into three groups, namely a control group, a group, in which zymosan A was used to induce inflammation (Zym group) and a PNS-treated group. Rats in the three groups were administered liquid paraffin (i.p.), zymosan A (20 mg/kg, i.p., once every 3 days) or zymosan A and PNS (100 mg/kg, i.p., once daily), respectively. All animals were fed a high-fat diet for 9 weeks. At scheduled times, rats were killed, blood was collected and the aorta was removed. Pathological changes in aortas were observed using Sudan IV staining and transmission electron microscopy. Serum lipids were measured enzymatically. Whole-blood viscosity was observed at different shear rates. The expression of cardiovascular disease-specific genes was determined using GEArray (SuperArray, Frederick, MA, USA). Western blotting was used to evaluate the expression levels of nuclear factor (NF)-kappaB/p65 and its inhibitor IkappaBalpha in the aortic wall. In the present study, typical pathological changes associated with atherosclerosis in rats following induction by zymosan A were alleviated by PNS treatment. In the PNS-treated group, there was a marked reduction in total serum cholesterol, triglycerides and blood viscosity. In addition, PNS treatment significantly decreased the gene expression of some inflammatory factors, such as integrins, interleukin (IL)-18, IL-1beta and matrix metalloproteinases 2 and 9. The expression of NF-kappaB/p65 was attenuated, whereas the expression of IkappaBalpha was significantly increased, after treatment with PNS. In conclusion, it appears that PNS exerts its therapeutic effects on atherosclerosis through an anti-inflammatory action and regulation of the blood lipid profile and that an NF-kappaB signalling pathway is involved.
以往的研究报道了三七总皂苷（PNS）的抗动脉粥样硬化作用。本研究的目的是探讨PNS抗动脉粥样硬化作用及其炎症反应的分子机制。将30只大鼠随机分为三组，即对照组、用酵母聚糖A诱导炎症的组（酵母聚糖组）和PNS治疗组。三组大鼠分别腹腔注射液体石蜡、酵母聚糖A（20 mg/kg，腹腔注射，每3天1次）或酵母聚糖A和PNS（100 mg/kg，腹腔注射，每天1次）。所有动物均给予高脂饮食9周。在预定时间，处死大鼠，采集血液并取出主动脉。用苏丹IV染色和透射电子显微镜观察主动脉的病理变化。酶法测定血脂。在不同剪切速率下观察全血粘度。使用GEArray（美国马萨诸塞州弗雷德里克市SuperArray公司）测定心血管疾病特异性基因的表达。采用蛋白质免疫印迹法评估主动脉壁中核因子（NF）-κB/p65及其抑制剂IκBα的表达水平。在本研究中，PNS治疗减轻了酵母聚糖A诱导的大鼠动脉粥样硬化相关的典型病理变化。在PNS治疗组中，血清总胆固醇、甘油三酯和血液粘度显著降低。此外，PNS治疗显著降低了一些炎症因子的基因表达，如整合素、白细胞介素（IL）-18、IL-1β以及基质金属蛋白酶2和9。PNS治疗后，NF-κB/p65的表达减弱，而IκBα的表达显著增加。总之，PNS似乎通过抗炎作用和调节血脂谱对动脉粥样硬化发挥治疗作用，并且涉及NF-κB信号通路。
