粥样硬化血管能量代谢障碍的初步研究
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摘要
目的：本实验主要观察在动脉粥样硬化的发生过程中能量负荷值的变化,用阿托伐他汀及曲美他嗪进行干预,探讨能量代谢障碍对动脉粥样硬化的影响。方法：1.40只6周龄雄性wistar大鼠,随机分为(1)A组(空白对照组)：饲以普通饲料；(2)B组(动脉粥样硬化组)：饲以高脂饲料(含普通饲料92.9%,胆固醇1%,胆酸钠0.5%,丙硫氧嘧啶0.6%,猪油5%),并分别于第一、二、三天腹腔注射总量为70万u／kg的维生素D注射液。(3)C组(阿托伐他汀干预组)：饲以高脂饲料,分别于第一、二、三天腹腔注射总量为70万u／kg的维生素D注射液,并每天灌胃阿托伐他汀0.5mg／只。(4)D组(曲美他嗪干预组)：饲以高脂饲料,分别于第一、二、三天腹腔注射总量为70万u／kg的维生素D注射液,并每天灌胃曲美他嗪1.5mg／只。2.12周末抽取活体大鼠心腔内血液2ml,注入含0.5%枸橼酸钠的检测管中,离心后行甘油三脂及总胆固醇检测。3.将大鼠主动脉从主动脉开口处分离至腹主动脉分支处,分为三份。4.一份行HE染色光镜下观察组织病变情况。5.一份剪碎后用0.25%胰酶消化3.5h,制成细胞悬液,用荧光探针DCFHDA标记,经流式细胞仪检测活性氧含量。6.一份于冰上制成组织匀浆,用高效液相色谱法检测能量负荷值。7.统计方法：结果采用均数加减标准差(x±S)表示,进行方差齐性检验,ONE-WAY AONVA方差分析,组间均数两两比较用LSD法,组间数据相关性分析采用直线相关分析,所有统计工作均由统计学软件SPSS17.0完成。结果：1.病理切片可见：B组管壁向管腔突出明显,内皮下大量泡沫细胞形成,表面纤维增生紊乱；C组及D组内皮下泡沫细胞形成,平滑肌细胞增生。2.B组甘油三酯及总胆固醇水平较A组明显增高,经阿托伐他汀及曲美他嗪干预后,其水平均有意义的下降。3.活性氧含量在B组较A组明显升高,经药物干预后,其水平明显下降。4.能量负荷值在B组较A组明显下降,经药物干预后,其水平明显增高。结论：1.喂养高脂饲料及注射维生素D可成功复制动脉粥样硬化模型。2.在动脉粥样硬化模型大鼠主动脉组织中,活性氧明显升高,说明氧化应激是动脉粥样硬化形成的机制之一。3.在动脉粥样硬化模型大鼠主动脉组织中,其细胞内能量负荷明显降低,提示能量代谢障碍参与了动脉粥样硬化的形成。4.阿托伐他汀干预后,细胞内活性氧及能量负荷明显改善,表明阿托伐他汀除降脂作用外,还能改善粥样硬化血管能量代谢障碍。5.曲美他嗪干预后,细胞内活性氧降低,能量负荷升高,显示曲美他嗪具有改善粥样硬化动脉能量代谢障碍的作用。
Objective:The main purpose of this experiment is to observe the change of Energe charge in the process of Atherosclerosis,and interfering the process with Atorvastatin and Trimetazidine,to investigate whether there is a possible mechanism that Energe charge can inducing Atherosclerosis. Methods: 1.Forty six-weeks-old wistar rats distribute into four groups randomly:(1)Group A (Black):to breed with ecumenic feed;(2)Group B(superlipoid feed):to breed with superlipoid feed(include 92.9% ecumenic feed,1% cholesterol,0.5% sodium cholate,0.6% propylthiouracil and 5% lard),and to inject vitamin D which volume dose is 700 thousand u/kg in the first、second and third day in peritoneal cavity.(3)Group C(Atorvastatin):to breed with superlipoid feed,and to inject vitamin D which volume dose is 700 thousand u/kg in the first、second and third day in peritoneal cavity,and to intragastric administration with Atorvastatin which dose is 0.5mg/d per one rat.(4)Group D(Trimetazidine):to breed with superlipoid feed,and to inject vitamin D which volume dose is 700 thousand u/kg in the first、second and third day in peritoneal cavity,and to intragastric administration with Trimetazidine which dose is 1.5mg/d per one rat.2.Afterl2 weeks,2ml blood was extracted from chambers of heart of alive rat,injected into a pipe with 0.5% sodium citrate,detected the content of Triglyceride and Total Cholesterol after being centrifugated.3.The aorta of rat was separated from the opening to where the descending aorta has the first arborization,and separated into three pieces.4.One piece was observed the condition of pathological changes after HE coloretur with light microscope.5.One piece was cutted into fragments,digested with 0.25% pancreatin for 3.5 hours,fabricated into cell suspension,marked with fluorescent probe DCFHDA,observed the content of reactive oxygen species by flow cytometer.6.One piece was fabricated into tissue homogenate on ice, observed the energe charge by high performance liquid chromatography.7.Statistical method:The results were showed by means plus or subtracting standard, observed the homoscedasticity,ONE-WAY AONVA,the deviation of between groups means we compared by LSD.The software SPSS 17.0 for windows was used to analyze the data. Results:In pathological sections we saw that vessel wall protruded into lumens apparently,a lot of foam cells formed under endothelial cells, superficial fibers increased and became mussy in Group B;some foam cells formed under endothelial cells and smooth muscle cell increased in Group C and D.2.The level of Triglyceride and total cholesterol in Group was apparently higher than Group A,and after the intervention of Atorvastatin and Trimetazidine,it decraesed significatively.3.The content of ROS in Group B was apparently higher than Group A,and after the intervention of drugs,is was decraesed apparently.4.The level of energe charge in Group B was was apparently lower than Group A,and after the intervention of drugs,is was raised apparently. Conclusion:1.The model of Atherosclerosis can be copied successfully by breeding superlipoid feed and injecting vitamin D.2.The level of ROS was apparently raised in the tissues of Atherosclerosis,it was explained that oxidative stress was one mechanism in the formation of Atherosclerosis.3.The level of Energe charge was apparently decreased in the aorta of Atherosclerosis,it was explained that energy metabolism impairment was one mechanism in the formation of Atherosclerosis.4.Atorvastatin can improve the level of ROS and Energe charge apparently,it was explained that Atorvastatin can improve energy metabolism of aorta besides its effect of reducing blood fat.5. Trimetazidine can decrease the level of ROS and raise the level of Energe charge,it was explained that Trimetazidine have the effect of improve energy metabolism impairment in Atherosclerosis.
Objective:The main purpose of this experiment is to observe the change of Energe charge in the process of Atherosclerosis,and interfering the process with Atorvastatin and Trimetazidine,to investigate whether there is a possible mechanism that Energe charge can inducing Atherosclerosis. Methods: 1.Forty six-weeks-old wistar rats distribute into four groups randomly:(1)Group A (Black):to breed with ecumenic feed;(2)Group B(superlipoid feed):to breed with superlipoid feed(include 92.9% ecumenic feed,1% cholesterol,0.5% sodium cholate,0.6% propylthiouracil and 5% lard),and to inject vitamin D which volume dose is 700 thousand u/kg in the first、second and third day in peritoneal cavity.(3)Group C(Atorvastatin):to breed with superlipoid feed,and to inject vitamin D which volume dose is 700 thousand u/kg in the first、second and third day in peritoneal cavity,and to intragastric administration with Atorvastatin which dose is 0.5mg/d per one rat.(4)Group D(Trimetazidine):to breed with superlipoid feed,and to inject vitamin D which volume dose is 700 thousand u/kg in the first、second and third day in peritoneal cavity,and to intragastric administration with Trimetazidine which dose is 1.5mg/d per one rat.2.Afterl2 weeks,2ml blood was extracted from chambers of heart of alive rat,injected into a pipe with 0.5% sodium citrate,detected the content of Triglyceride and Total Cholesterol after being centrifugated.3.The aorta of rat was separated from the opening to where the descending aorta has the first arborization,and separated into three pieces.4.One piece was observed the condition of pathological changes after HE coloretur with light microscope.5.One piece was cutted into fragments,digested with 0.25% pancreatin for 3.5 hours,fabricated into cell suspension,marked with fluorescent probe DCFHDA,observed the content of reactive oxygen species by flow cytometer.6.One piece was fabricated into tissue homogenate on ice, observed the energe charge by high performance liquid chromatography.7.Statistical method:The results were showed by means plus or subtracting standard, observed the homoscedasticity,ONE-WAY AONVA,the deviation of between groups means we compared by LSD.The software SPSS 17.0 for windows was used to analyze the data. Results:In pathological sections we saw that vessel wall protruded into lumens apparently,a lot of foam cells formed under endothelial cells, superficial fibers increased and became mussy in Group B;some foam cells formed under endothelial cells and smooth muscle cell increased in Group C and D.2.The level of Triglyceride and total cholesterol in Group was apparently higher than Group A,and after the intervention of Atorvastatin and Trimetazidine,it decraesed significatively.3.The content of ROS in Group B was apparently higher than Group A,and after the intervention of drugs,is was decraesed apparently.4.The level of energe charge in Group B was was apparently lower than Group A,and after the intervention of drugs,is was raised apparently. Conclusion:1.The model of Atherosclerosis can be copied successfully by breeding superlipoid feed and injecting vitamin D.2.The level of ROS was apparently raised in the tissues of Atherosclerosis,it was explained that oxidative stress was one mechanism in the formation of Atherosclerosis.3.The level of Energe charge was apparently decreased in the aorta of Atherosclerosis,it was explained that energy metabolism impairment was one mechanism in the formation of Atherosclerosis.4.Atorvastatin can improve the level of ROS and Energe charge apparently,it was explained that Atorvastatin can improve energy metabolism of aorta besides its effect of reducing blood fat.5. Trimetazidine can decrease the level of ROS and raise the level of Energe charge,it was explained that Trimetazidine have the effect of improve energy metabolism impairment in Atherosclerosis.
引文
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3. Williams H, Johnson J L, Carson K G, et al. Characteristics of intact and ruptured atherosclerotic plaques in brachiocephalic arteries of apolipoprotein E knockout mice [J]. Arterioscler Thromb Vasc Biol, 2002;22(5):788-792
4.沈丽,卢维晟,姚俊字,,等.不同方法建立动脉粥样硬化大鼠模型的比较[J].心脏杂志,2005；17(1)：18-20
5.赵娟,李相军,孙波,等.维生素D3联合高脂饲料建立大鼠动脉粥样硬化模型[J].实用医学杂志,2009；25(21)：3569-3571
6. Koike K,Moore EE.Phospholipa. Az inhibitor decouples lung injury from gut ischemiareperfusion.Surgery,1992; 1:173-179
7.张陵,万宁.氧自由基脂质过氧化反应所致运动性疲劳产生机制研究进展.中国实验诊断学,2006；10(9)：104-108
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