蒺藜总皂苷对动脉粥样硬化家兔细胞核因子κB及血清炎症标志物水平的影响

Effects of gross saponins from tribulus terrestris on nuclear factor kappa B and specific markers of inflammation in atherosclerotic rabbits

目的:观察蒺藜总皂苷对动脉粥样硬化家兔组织细胞核因子κB、血清炎症标志物水平的影响。方法:实验于2004-12/2005-05在中国中医研究院西苑医院心血管实验室完成。50只健康雄性日本大耳白兔,随机取10只作为正常对照组,喂普通饲料,其余40只给予高脂饮食喂养4周后,再随机分为4组:①模型组10只,继续喂高脂饲料。②小剂量组10只,喂以高脂饲料和蒺藜总皂苷6.3mg/(kg·d)。③大剂量组10只,喂高脂饲料和蒺藜总皂苷12.6mg/(kg·d)。④阳性药物对照组10只,喂以高脂饲料和辛伐他汀2.35mg/(kg·d)。2周后,测定血脂、组织中细胞核因子κB及ELISA法测定血清炎症标志物血清C-反应蛋白、单核细胞趋化蛋白1、血管细胞黏附分子1水平。结果:50只家兔均进入结果分析。①与正常对照组相比,模型组、小剂量组、大剂量组、阳性药物对照组血清胆固醇及三酰甘油均升高[(1.03±0.50),(24.33±6.08),(17.10±1.94),(14.81±5.03),(16.81±2.73)mmol/L,P<0.01;(0.87±0.43),(5.27±0.06),(2.83±0.16),(1.84±0.40),(2.20±0.74)mmol/L,P<0.01];与模型组相比,小剂量组、大剂量组、阳性药物对照组血清胆固醇及三酰甘油水平均明显降低(P<0.05)。②正常对照组细胞核因子κB呈现低表达状态,阳性表达出现在胞浆中;模型组细胞核因子κB活化,表达增强,阳性颗粒出现在胞浆及胞核中,小剂量、大剂量组、阳性药物对照组细胞核因子κB表达的活性较模型组低[(15.47±6.32)%,(8.54±2.67)%,(4.36±3.65)%,(4.70±3.69)%,P<0.05],胞核阳性表达减少。小剂量、大剂量组比较差异不显著。③与模型组比较,小、大剂量组及阳性药物对照组C反应蛋白、血管细胞黏附分子1水平显著降低[(57.09±8.03),(40.07±4.65),(42.04±8.57),(26.07±5.15)ng/L,P<0.01;(51.74±9.29),(43.38±4.09),(36.04±2.57),(35.09±2.49)ng/L,P<0.01],大剂量组血清单核细胞趋化蛋白-1明显降低[(38.77±8.30),(29.47±10.25)ng/L,P<0.05),小剂量组及阳性药物对照组血清单核细胞趋化蛋白-1无明显变化。结论:蒺藜总皂苷能够降低血脂、减少动脉粥样硬化病灶中细胞核因子κB的激活,降低血清中C反应蛋白、单核细胞趋化蛋白1、血管细胞黏附分子1的含量,蒺藜总皂苷具有抗动脉粥样硬化作用。

AIM： To observe the effects of gross saponins from tribulus terrestris （GSTT） on the expression of nuclear factor kappa B（NF-κB） and specific markers of inflammation in rabbits with atherosclerosis. METHODS： The experiment was conducted in the Laboratory of Cardiovascular Diseases, Xiyuan Hospital, China Academy of Traditional Chinese Medicine from December 2004 to May 2005. Fifty healthy male Japanese white rabbits were used in the experiment, 10 of them were randomly selected as controls and allocated normal diet for 4 weeks. The resting 40 rabbits were fed with hypercholesterol for 4 weeks and then randomized into four groups, with 10 rabbits in each：①Model rabbits were fed with hypercholesterol diet. ②Low-dose GSTF group were given hypercholesterol and 6.3 mg/kg GSTF daily.③High-dose GSTF group were fed with hypercholesterol and 12.6 mg/kg GSTF daily.④Positive control group was treated with hypercholesterol and 2.35 mg/kg simvastatin everyday. After rabbits were given medicine for 2 weeks, the levels of blood lipid, NF-κB, C-reactive protein （CRP）, monocyte chemoattractant protein-1 （MCP-1） and vascular cell adhesion molecule-1 （VCAM-1） were determined by ELISA method. RESULTS： Totally fifty rabbits were involved in the result analysis.①Compared with normal control group, the levels of serum cholesterol and triglyceride （TG） were elevated in low-dose GSTF, high-dose GSTF, positive control and model groups [（1.03 ±0.50）, （24.33±6.08）, （17.10±1.94）, （14.81±5.03）, （16.81±2.73） mmol/L, P 〈 0.01; （0.87±0.43）, （5.27±0.06）, （2.83±0.16）, （1.84±0.40）, （2.20±0.74） mmol/L, P 〈 0.01]. Compared with model group, the levels of serum cholesterol and TG were decreased significantly in low-dose GSTF, high-dose GSTF and positive control groups （P 〈 0.05）.②NF-κB expressed lowly in normal control group, and positively in plasm; In model group, the expression of activated NF-κB was increased, and positive in plasm and nucleus. The low-dose GSTF, high-dose GSTF and positive control groups presented lower expression of NF-κB in the nucleus than model group [（15.47±6.32）%, （8.54±2.67）%, （4.36±3.65）%, （4.70±3.69）%, P 〈 0.05]. There was insignificant difference between lowdose GSTT and high-dose GSTT groups.③Compared with model group, the levels of CRP and VCAM-1 were significantly decreased in low-dose GSTT, high-dose GSTT and positive control groups [（57.09±8.03）, （40.07±4.65）, （42.04±8.57）, （26.07±5.15） ng/L, P 〈 0.01; （51.74±9.29）, （43.38±4.09）, （36.04±2.57）, （35.09±2.49） ng/L, P 〈 0.01]. The high-dose GSTF group demonstrated significantly lower level of MCP-1 in serum [（38.77±8.30）, （29.47±10.25） ng/L, P 〈 0.05], while there was no obvious change in lowdose GSTF and positive control groups.CONCLUSION： GSTT can be against atherosclerosis by decreasing the level of blood lipid, reducing the expression of NF-κB and decreasing the levels of specific markers of inflammation in serum.