NLRP3炎症小体在早期动脉粥样硬化ZDF大鼠中的表达及阿托伐他汀的干预  

Expression of NLRP3 inflammasome in early atherosclerosis ZDF rats and intervention effect of atorvastatin

作　　者：马全鑫[1] 杨钦钦[1] 陆晔枫[2] 陈小真[1] 陈诚[1] 寿旗扬[1] 蔡月琴[1] 陈民利[1] 

机构地区：[1]浙江中医药大学动物实验研究中心/比较医学研究中心,杭州310053 [2]扬州大学兽医学院,扬州225009

出　　处：《中国比较医学杂志》2015年第2期1-6,F0002,共7页Chinese Journal of Comparative Medicine

基　　金：浙江省自然科学基金(LY12C04002)

摘　　要：目的观察NLRP3炎症小体及其介导的炎症因子在早期动脉粥样硬化(AS)Zucker糖尿病肥胖(ZDF)大鼠主动脉组织中的表达,以及阿托伐他汀(ATV)的干预作用。方法高脂饲喂联合小剂量多次注射VD3建立ZDF大鼠早期AS模型,并给予ATV干预;检测血糖血脂、胰岛素、ox-LDL和hs CRP,并进行主动脉组织病理学检查和NLRP3、caspase 1、IL-1β和TNF-α基因表达的检测。结果高脂饲喂后ZDF大鼠血糖、血脂、胰岛素和oxLDL水平均显著上升(P<0.05)。注射VD3后,hs CRP水平均显著上升(P<0.05),主动脉组织出现明显的早期AS病变,且NLRP3、caspase 1、IL-1β和TNF-α基因表达显著上调(P<0.05),而ATV组ZDF大鼠血脂、ox-LDL和hs CRP水平均明显下降(P<0.05),AS病变程度减轻,且主动脉组织中NLRP3、Caspase 1、IL-1β和TNF-α基因表达显著下调(P<0.05)。结论 NLPR3炎症小体及其介导的炎症因子参与了ZDF大鼠早期AS的炎症反应,而ATV可抑制NLRP3炎症小体的表达,抑制AS的炎症反应。Objective To observe the expression of NLRP3 inflammasome and its mediated inflammatory factors in the aorta of Zuker diabetic fatty（ ZDF） rats with early atherosclerosis（ AS）,and observe the intervention effect of atorvastatin. Methods ZDF rats models of type 2 diabetes mellitus（ T2DM） and AS were established by feeding high-fat diet accompanied with multiple injections of vitamin D3（ VD3）. Meanwhile,half of these rats were also given atorvastatin（ ATV）. Changes of serum glucose,lipids,insulin,ox-LDL and hs CRP were tested. Morphological changes of aorta tissues were examined by histopathology. The gene expressions of NLRP3 and some other inflammatory mediators were also quantified. Results After feeding high-fat diet,the glucose,lipids,insulin and ox-LDL levels of ZDF rats in the model group were significantly increased（ P〈0. 05）. After VD3 injecting,pathological changes also occurred in the early stageAS. Moreover,the hs CRP level was increased along with elevated gene expressions of NLRP3,caspase 1,IL-1β and TNF-α in the aorta tissues（ P〈0. 05）. Nevertheless,the serum glucose,lipids,insulin,ox-LDL and hs CRP levels in ZDF rats of the ATV group were significantly decreased（ P〈0. 05）. The pathological changes were attenuated and gene expressions of NLRP3,caspase-1,IL-1β and TNF-α in the aorta tissues also significantly reduced（ P〈0. 05）. Conclusions NLPR3 inflammasome and its mediated inflammatory mediators participate in the inflammatory responses during the early AS development. ATV can inhibit the gene expression of NLRP3 inflammasome,and alleviate the inflammatory responses during atherosclerosis.

关 键 词：动脉粥样硬化 NLRP3炎症小体 2型糖尿病 ZDF大鼠 

分 类 号：R33[医药卫生—人体生理学]