缬沙坦对高脂饮食喂养家兔核因子-κB及炎症因子表达的影响  

The effects of valsartan on nuclear factor-κB and inflammatory factors expression in rabbit fed with high-lipid diet

作　　者：王斌[1] 管思明[1] 李西栋[1] 

机构地区：[1]华中科技大学同济医学院附属协和医院老年病科,湖北武汉430022

出　　处：《中国医院药学杂志》2008年第9期683-686,共4页Chinese Journal of Hospital Pharmacy

基　　金：中央保健委员会资助课题(编号:鄂C015)

摘　　要：目的:研究缬沙坦对高脂饮食喂养家兔NF-κB(nuclear factor-κB)及炎症因子表达的影响,从而明确其抗动脉粥样硬化的机制。方法:家兔主动脉病理切片观察光镜下血管壁结构的变化;ELISA(enzyme linked i mmunosorbent assay)法检测血清CRP(C-reactive protein)、IL-1(interleukin-1)及TNF-α(tumor necrosis factor-α);RT-PCR(reverse transcription-polymerasechain raction)法检测胸主动脉NF-κB mRNA的表达,EMSA(electrophoretic mobility shift assay)测定NF-κB的活性。结果:高脂饮食喂养家兔主动脉内膜有明显的粥样硬化斑块形成;经缬沙坦治疗后主动脉粥样硬化斑块明显变小。高脂饮食喂养后可明显增加血清CRP、IL-1及TNF-α的水平[分别为(2.6±0.8)mg·L-1与(11.7±2.2)mg·L-1,(12.8±1.6)ng·L-1与(44.9±4.1)ng·L-1,(41.4±2.9)ng·L-1与(80.2±5.7)ng·L-1,P<0.01],并明显增加胸主动脉NF-κB mRNA表达[(0.95±0.10)与(4.4±1.0),P<0.01],同时升高NF-κB与DNA的结合活性[(3.9±0.7)与(13.4±3.0),P<0.01];与高脂饮食组比较,缬沙坦可明显降低血清CRP、IL-1及TNF-α的水平[分别为(11.7±2.2)mg·L-1与(4.8±1.5)mg·L-1,(44.9±4.1)mg·L-1与(26.2±4.9)mg·L-1,(80.2±5.7)ng·L-1与(60.0±6.7)ng·L-1,P<0.01],胸主动脉NF-κB的mRNA表达及其活性也明显降低[分别为(4.4±1.0)与(2.1±0.7),(13.4±3.0)与(5.5±1.2),P<0.01]。NF-κB的结合活性与CRP,IL-1及TNF-α均呈正相关,r分别为0.93,0.91,0.90。结论:缬沙坦可明显抑制高脂饮食喂养家兔动脉粥样硬化斑块的形成,其机制可能为通过抑制NF-κB的表达及其活性,从而抑制炎症因子的表达所致。OBJECTIVE To investigate the effects of valsartan on nuclear factor-κB （NF-κB） and inflammatory factors expression and elucidate its mechanism of anti-αtherosclerosis in rabbits fed by high-lipid diet. METHODS The constitution of vessel wall was observed through pathological method. The levels of C-reactive protein （CRP）, interleukin-1 （IL-1） and tumor necrosis factor-α （TNF-α） were all determinated by enzyme linked immunosorbent assay （ELISA）. The mRNA and activity of NF-κB were detemainated by reverse transcription-polymerase chain raction （RT-PCR） and electrophoretic mobility shift assay （EMSA）, respectively. RESULTS There were evident atherosclerotic plaques in thoracic aorta of rabbits fed by high-lipid diet. However, the valsartan could significantly inhibit the formation of atherosclerotic plaques. After fed by high-lipid diet, the levels of CRP, IL-1 and TNF-α were significantly increased （2.6±0.8） mg·L^-1 vs （11.7±2.2） mg·L^-1,（12. 8±1.6） ng·L^-1 vs （44.9±4.1） ng·L^-1,（41.4±2.9） ng·L^-1 vs （80.2±5.7） ng·L^-1, P〈0. 01 ） and the mRNA and the hinging activity of NF-κB in aorta of rabbits were also significantly increased （0. 95 ± 0. 10） vs （4. 4 ± 1.0） and （3. 9 ±0. 7） vs （13.4 ± 3. 0）, respectively, all P〈0. 01）. Compared with high-lipid group, the valsartan could significantly decrease the levels of CRP,IL-1 and TNF-α [（11.7 ± 2. 2） mg·L^-1 vs （4. 8 ± 1.5） mg·L^-1 , （44. 9 ± 4. 1） mg·L^-1 vs （26. 2 ± 4. 9） mg·L^-1, （80. 2 ± 5. 7） ng·L^-1 vs （60. 0 ± 6. 7） ng·L^-1 ,P〈0. 01] and could also significantly decrease the levels of the mRNA and the hinging activity of NF-κ [（4.4 ± 1.0） vs （2. 1 ± 0. 7）, （13. 4 ± 3. 0） vs （5. 5 ± 1.2） ,P〈0. 01]. And the activity of NF-κB and CRP, IL-1 and TNF-α all had positive correlation. The correlation coefficient was 0. 93,0. 91 and 0. 90, respectively. CONCLUSION The valsartan has significant effect on anti-athero

关 键 词：缬沙坦 C-反应蛋白 白介素-1 肿瘤坏死因子-α 核因子-ΚB 动脉粥样硬化 

分 类 号：R966[医药卫生—药理学]