Ca^(2+)阻滞剂非洛地平对高脂饮食SD大鼠颈动脉球囊损伤后内膜增生的影响

Effect of Ca^(2+) blocker on neointimal hyperplasia of balloon injured carotid artery in SD rats

目的观察Ca2+阻滞剂非洛地平对高脂饮食SD大鼠颈动脉球囊损伤后动脉内膜增生的影响。方法2F球囊导管造成大鼠颈动脉内膜剥脱后,将27只大鼠随机分为3组,标准饲料组,高脂饲料组、高脂饲料+非洛地平组(5mg.kg-1.day-1)。给药3个月测定血压后,腹主动脉取血,并行腹主动脉插管灌注固定颈总动脉,HE(苏木素/伊红)染色,用图象分析仪观察颈总动脉血管腔面积(L)、血管壁(中膜)面积(W),并计算其比值(W/L)。分光光度计分别测定血浆谷胱甘肽水平及谷胱甘肽过氧化酶、谷胱甘肽还原酶活性。结果高脂饲料组SD大鼠血浆甘油三酯(triglyceride,TG)、胆固醇(cholesterol,TC)、LDL水平较标准饲料组明显增高(P<0.05),与高脂饲料组比较,非洛地平组血浆脂质代谢产物MDA水平显著降低(P<0.05),GXH、高密度脂蛋白胆固醇(high densitylipoprotein-cholesterol,HDL-C)水平明显升高(P<0.05),皿浆谷胱甘肽还原酶及其过氧化酶活性明显增强(P<0.05);损伤颈动脉高脂饲料组明显增厚,局部并有斑块形成。非洛地平组W/L明显著小于高脂饲料组(P<0.05)。结论(1)Ca阻滞剂可降低高脂饮食SD大鼠颈动脉球囊损伤后内膜增生;(2)Ca阻滞剂可增加SD大鼠血浆谷胱甘肽,谷胱甘肽过氧化酶、谷胱甘肽还原酶活性,降低血脂代谢产物MDA水平。(3)高脂条件氧化还原产物失衡可能是血管内膜损伤后增生的重要因素。

OBJECTIVE To observe the effect of Ca^2＋ blocker（felodipine） on neointimal hyperplasia of the balloon injured carotid artery in SD rats. METHODS A 2F Foley＇s tube was used to develop a rat carotid artery neointimal hyperplasia modelby endothelial denudation in 27 SD rats. Then, the 27 SD rats were randomly divided into three groups, standard chow（ Group NC, n = 9 ）, high-fat diet（ Group HF, n = 9 ）or Felodipine （100 mg · kg^-1·day^-1） ＋ high- fat diet（ Group CB ,n = 9）. After the three month, blood pressure was measured, and the abdominal artery was cannulated for fixation of the carotid artery. The area of lumina, the thickness of wall and the ratio of wall to Lanen of the carotid artery were obtained using an image analysis system. Serum cysteinylglycine levels as well as serum glutathione peroxidase and reductase activity were determined by spectrum meter. RESULTS The serum levels of TG,TCand LDL were significantly increased in Group HF compared with those in Group NC （ P 〈 0. 05 ）. In Group CB ,the serum levels of cysteinylglycine and HDL-C were significantly increased while serum MDA（ the metabolic product of lipoids）was significantly decreased,and the serum glutathione peroxidase and reductase activity significantly enhanced when compared with Group HF（ P 〈 0. 05 ）. on the injured sides of the carotid artery, significant thickening and local plaque formation were observed in the HF Group, whose W/L ratio of the carotid artery was significantly higher than Group CH （ P 〈 0. 05 ） ; CONCLUSION （ 1 ） Ca^2＋ -blocker can ameliorate the neointimal hyperplasia of the balloon injured carotid artery in SD fed with high-fatdiet. （2） Ca^2＋-blocker can increase serum cysteinylglycine levels and enhance the activity of glutathione peroxidase and reductase, while reduce serum MDA levels. （3） The disequilibrium of oxidoreduction products under the condition of hyperlipid may be an important reason of neointimal hyperplasia after vessel injury.