高尿酸血症对冠状动脉粥样硬化性心脏病大鼠炎性指标及氧化型低密度脂蛋白与凝集素样氧化型低密度脂蛋白受体1水平的影响

Effects of hyperuricemia on inflammatory factors, oxidized low-density lipoprotein and lectin-like oxidized low-density lipoprotein receptor-1 in rats with coronary atherosclerotic heart disease

目的分析高尿酸血症对冠状动脉粥样硬化性心脏病（冠心病）大鼠炎性指标及氧化型低密度脂蛋白（ox-LDL）与凝集素样氧化型低密度脂蛋白受体1（LOX-1）水平的影响。方法选取90只清洁级健康雄性Sprague-Dawley大鼠，采用随机数字表法分为对照组、冠心病组、冠心病合并高尿酸血症组，各30只。冠心病组给予高脂肪饮食同时腹腔注射维生素D3，冠心病合并高尿酸血症组给予高脂肪饮食及尿酸酶抑制剂（氧嗪酸钾）灌胃，对照组给予0.9%氯化钠注射液腹腔注射。比较3组大鼠的C反应蛋白（CRP）、肿瘤坏死因子α（TNF-α）、基质金属蛋白酶9（MMP-9）、ox-LDL、低密度脂蛋白（LDL）及LOX-1水平，并比较3组冠状动脉内膜组织病理特征。结果冠心病合并高尿酸血症组大鼠血清CRP、TNF-α、MMP-9、ox-LDL、LDL及LOX-1水平均明显高于冠心病组及对照组，差异均有统计学意义［（11.1±2.2）μg/L比（8.4±1.6）、（4.1±1.4）μg/L，（165±39）ng/L比（147±36）、（62±21）ng/L，（90±66）ng/L比（58±42）、（36±12）ng/L，（393±81）μg/L比（242±91）、（113±51）μg/L，（3.26±1.01）mmol/L比（2.41±0.61）、（1.05±0.41）mmol/L，（384±72）μg/L比（268±46）、（142±24）μg/L］（均P＜0.05）。冠心病合并高尿酸血症组大鼠冠状动脉内膜组织病理损伤最重，部分区域出现脂质沉积现象，泡沫细胞形成较少，有溃疡出现。结论高尿酸血症同冠心病密切相关，血尿酸水平升高可促进炎性反应，促使ox-LDL与LOX-1进一步升高。

ObjectiveTo investigate effects of hyperuricemia on inflammatory factors, oxidized low-density lipoprotein（ox-LDL） and lectin-like oxidized low-density lipoprotein receptor-1（LOX-1） in rats with coronary atherosclerotic heart disease（CHD）. MethodsNinety clean grade healthy male Sprague-Dawley rats were randomly divided into control group, CHD group, CHD complicated with hyperuricemia group, with 30 rats in each group. The CHD group had high fat diet and intraperitoneal injection of vitamine D3; the CHD complicated with hyperuricemia group had high fat diet and intragastric administration of uricase inhibitor potassium oxonate; the control group had intraperitoneal injection of 0.9% sodium chloride sodium. Levels of C-reactive protein（CRP）, tumor necrosis factor-α（TNF-α）, matrix metalloproteinase-9（MMP-9）, ox-LDL, LDL, LOX-1 and pathological features of coronary artery intima were analyzed. ResultsLevels of serum CRP, TNF-α, MMP-9, ox-LDL, LDL and LOX-1 in CHD complicated with hyperuricemia group were significantly higher than those in CHD group and control group[（11.1±2.2）μg/L vs （8.4±1.6）,（4.1±1.4）μg/L; （165±39）ng/L vs （147±36）,（62±21）ng/L; （90±66）ng/L vs （58±42）,（36±12）ng/L; （393±81）μg/L vs （242±91）,（113±51）μg/L; （3.26±1.01）mmol/L vs （2.41±0.61）,（1.05±0.41）mmol/L; （384±72）μg/L vs （268±46）,（142±24）μg/L]（P〈0.05）. Rats in CHD combined with hyperuricemia group had the most severe coronary artery intimal damage; lipid deposition was observed in some areas; foam cell formation decreased and ulceration occurred. ConclusionHyperuricemia is closely related to CHD; elevation of serum uric acid can promote inflammatory response and increase levels of ox-LDL and LOX-1.