普罗布考联合阿托伐他汀对糖尿病动脉粥样硬化大鼠氧化应激水平的影响
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摘要
目的观察普罗布考联合阿托伐他汀对糖尿病动脉粥样硬化大鼠超氧化物歧化酶(SOD)-氧化应激指标水平变化。方法 32只雄性8周龄Wister大鼠随机分为正常对照组(C)、糖尿病组(D)、糖尿病普罗布考治疗组(P)、糖尿病阿托伐他汀与普罗布考联合治疗组(U),给予灌胃8周后处死,采血分离血清测胆固醇(TC),甘油三酯(TG),高密度脂蛋白(HDL),低密度脂蛋白(LDL),血清丙二醛(MDA)、SOD、8异前列腺素(8-isoPGF2α)、血小板内皮细胞黏附分子(PECAM-1)水平变化。结果与C组相比,D组血清TC、TG、DL升高,HDL下降,血清MDA、8-iso-PGF2α、PECAM-1明显增加,SOD水平明显降低(P均<0.01);P组、U组TC-LDL较D组大鼠水平均降低;MDA、8-iso-PGF2α均显著下降,SOD水平均显著升高(P均<0.01);PECAM-1水平显著下降(P<0.01);其中联合治疗组与单独用药组相比,降低幅度更明显(P<0.01)。结论普罗布考与阿托伐他汀,可减少糖尿病动脉粥样硬化大鼠的氧化应激损伤,延缓动脉粥样硬化发展,二者联用,效果更佳。
Objective To determine the effects of Probucol and Atorvastatin on the changes of oxidative stress levels such as superoxide dismutase(SOD) in rats with diabetes and atherosclerosis. Methods Thirty-two male Wister rats aged 8 weeks were randomly divided into normal control group(group C), diabetes group(group D), diabetes+Probucol group(group P), and diabetes+Atorvastatin and Probucol group(group U). The rats were sacrificed at 8 weeks after gavage. Blood samples were taken to isolate serum and measure the changes of cholesterol(TC),triglyceride(TG), high density lipoprotein(HDL), low density lipoprotein(LDL), serum malondialdehyde(MDA),SOD, 8-isoprostane(8-iso-PGF2α) and PECAM-1 levels. Results Compared with group C, the serum TC, TG and LDL levels increased, HDL level decreased, serum MDA, 8-iso-PGF2α and PECAM-1 levels increased significantly,and SOD level decreased significantly in group D(all P<0.01).Compared with group D,the TC and LDL levels decreased, MDA and 8-iso-PGF2α levels decreased significantly, SOD level increased significantly(all P<0.01), and PECAM-1 level decreased significantly(P<0.01) in group P and group U.The indexes decreased more significantly in the combination treatment group than those in the single treatment group(P<0.01).Conclusion Probucol and Atorvastatin may reduce oxidative stress injury and delay the development of atherosclerosis in rats with diabetes and atherosclerosis, and the combination of the two drugs is more effective.
Objective To determine the effects of Probucol and Atorvastatin on the changes of oxidative stress levels such as superoxide dismutase(SOD) in rats with diabetes and atherosclerosis. Methods Thirty-two male Wister rats aged 8 weeks were randomly divided into normal control group(group C), diabetes group(group D), diabetes+Probucol group(group P), and diabetes+Atorvastatin and Probucol group(group U). The rats were sacrificed at 8 weeks after gavage. Blood samples were taken to isolate serum and measure the changes of cholesterol(TC),triglyceride(TG), high density lipoprotein(HDL), low density lipoprotein(LDL), serum malondialdehyde(MDA),SOD, 8-isoprostane(8-iso-PGF2α) and PECAM-1 levels. Results Compared with group C, the serum TC, TG and LDL levels increased, HDL level decreased, serum MDA, 8-iso-PGF2α and PECAM-1 levels increased significantly,and SOD level decreased significantly in group D(all P<0.01).Compared with group D,the TC and LDL levels decreased, MDA and 8-iso-PGF2α levels decreased significantly, SOD level increased significantly(all P<0.01), and PECAM-1 level decreased significantly(P<0.01) in group P and group U.The indexes decreased more significantly in the combination treatment group than those in the single treatment group(P<0.01).Conclusion Probucol and Atorvastatin may reduce oxidative stress injury and delay the development of atherosclerosis in rats with diabetes and atherosclerosis, and the combination of the two drugs is more effective.
引文
[1]蒋美媛,庞明,黄东挺,等.普罗布考联合阿司匹林、阿托伐他汀治疗老年颈动脉粥样硬化的临床观察[J].广西医学,2012,34(10):1325-1326.
[2] Li H,Horke S,Forstermann U.Vascular oxidative stress,nitric oxide and atherosclerosis[J].Atherosclerosis,2014,237(1):208-219.
[3] Brownlee M.The pathobiology of diabetic complications,a unifying mechanism[J].Diabetes,2005,54:1615-1618.
[4]罗秀忠.阿托伐他汀联合普罗布考治疗狭窄性动脉粥样硬化斑块的疗效观察[J].中国现代医生,2010,48(11):147-148.
[5]巫颖,李绍发.普罗布考联合阿托伐他汀钙对高血压病患者颈动脉粥样硬化斑块的影响[J].临床荟萃,2011,26(15):1293-1296.
[6] Susztak K,Raff AC,Schiffer M,et al. Glucose-induced reactive oxygen species cause apoptosis of podocytes and podocyte depletion at the onset of diabetic nephropathy[J].Diabetes,2006,55:225-233.
[7] Lee EA,Seo JY,Jiang Z,et al. Reactive oxygen species mediate hilgh glucose-induced plasminogen activator inhibitor-1 up-regulation in mesangial cells and in diabetic kidney[J].Kidney Int,2005,67(5):1762-71.
[8]周智广,庞翠军.糖尿病大血管病变的发病基础与防治策略[J].中国医师杂志,2006,8(1):1-2.
[9]傅阳,李拥军,李涛,等.颈动脉超声Crouse积分法评价颈动脉斑块与血压、血脂及血尿酸的关系[J].临床荟萃, 2014,29(4):405-409.
[10]杨越,赵轲,顾大东.老年无症状性脑梗死患者颈动脉粥样硬化及其血清Hcy、hs-CRP水平的改变[J].中华全科医学,2015,13(10):1635-1637.
[11] Morrow JD.Quantification of isoprostanes as indices of oxidant stress and the risk of atherosclerosis in humans[J].Arterioseler Thromb Vasc Biol,2005,25(2):279-286.
[12]高淑磊,高爱武,刘俊红,等.高血压与氧化应激相关性研究[J].河北医药,2011,33(18):2770.
[13]王远程,叶志斌,周钦,等.丙丁酚抑制氧化型低密度脂蛋白诱导系膜细胞转化生长因子-β1表达[J].复旦学报(医学版),2005,32(2):151-154,188.
[2] Li H,Horke S,Forstermann U.Vascular oxidative stress,nitric oxide and atherosclerosis[J].Atherosclerosis,2014,237(1):208-219.
[3] Brownlee M.The pathobiology of diabetic complications,a unifying mechanism[J].Diabetes,2005,54:1615-1618.
[4]罗秀忠.阿托伐他汀联合普罗布考治疗狭窄性动脉粥样硬化斑块的疗效观察[J].中国现代医生,2010,48(11):147-148.
[5]巫颖,李绍发.普罗布考联合阿托伐他汀钙对高血压病患者颈动脉粥样硬化斑块的影响[J].临床荟萃,2011,26(15):1293-1296.
[6] Susztak K,Raff AC,Schiffer M,et al. Glucose-induced reactive oxygen species cause apoptosis of podocytes and podocyte depletion at the onset of diabetic nephropathy[J].Diabetes,2006,55:225-233.
[7] Lee EA,Seo JY,Jiang Z,et al. Reactive oxygen species mediate hilgh glucose-induced plasminogen activator inhibitor-1 up-regulation in mesangial cells and in diabetic kidney[J].Kidney Int,2005,67(5):1762-71.
[8]周智广,庞翠军.糖尿病大血管病变的发病基础与防治策略[J].中国医师杂志,2006,8(1):1-2.
[9]傅阳,李拥军,李涛,等.颈动脉超声Crouse积分法评价颈动脉斑块与血压、血脂及血尿酸的关系[J].临床荟萃, 2014,29(4):405-409.
[10]杨越,赵轲,顾大东.老年无症状性脑梗死患者颈动脉粥样硬化及其血清Hcy、hs-CRP水平的改变[J].中华全科医学,2015,13(10):1635-1637.
[11] Morrow JD.Quantification of isoprostanes as indices of oxidant stress and the risk of atherosclerosis in humans[J].Arterioseler Thromb Vasc Biol,2005,25(2):279-286.
[12]高淑磊,高爱武,刘俊红,等.高血压与氧化应激相关性研究[J].河北医药,2011,33(18):2770.
[13]王远程,叶志斌,周钦,等.丙丁酚抑制氧化型低密度脂蛋白诱导系膜细胞转化生长因子-β1表达[J].复旦学报(医学版),2005,32(2):151-154,188.