阿托伐他汀对高脂饮食糖尿病大鼠主动脉几丁质酶-3样蛋白-1表达的影响

Atorvastatin ameliorates aortic YKL-40 level in diabetic rats fed with an atherogenic diet

目的:观察阿托伐他汀对高脂饮食饲养糖尿病Sprague-Dawley(SD)大鼠主动脉炎症因子几丁质酶-3样蛋白-1(YKL-40)表达水平的影响。方法:SD大鼠被随机分为五组:正常饮食组,高脂饮食组,高脂饮食阿托伐他汀干预组,高脂饮食合并糖尿病组,高脂饮食合并糖尿病阿托伐他汀干预组,每组9只。高脂模型是单次腹腔内注射维生素D3和辅以高脂饮食;腹腔内注射链脲佐霉素(STZ)造模成糖尿病。阿托伐他汀治疗(20mg/kg)8周后,测定各组空腹血糖(FBG)、糖化血红蛋白(HbA1c)、甘油三酯(TG)和总胆固醇(TC)水平,半定量PCR和Real-time PCR测定大鼠主动脉YKL-40的mRNA表达水平,免疫组化评价主动脉内膜YKL-40的表达。结果:高脂饮食合并糖尿病组SD大鼠FBG、HbA1c和TG水平明显高于正常饮食组(P均<0.01)和高脂饮食组(P均<0.05)。YKL-40的mRNA表达水平在高脂饮食组明显高于正常饮食组(P<0.01),尤其在高脂饮食合并糖尿病大鼠中表达最高;免疫组化的结果也显示高脂饮食合并糖尿病大鼠的主动脉内膜YKL-40蛋白表达最高。经阿托伐他汀治疗后,YKL-40蛋白和mRNA表达水平均下调(P均<0.01)。结论:阿托伐他汀明显降低高脂饮食糖尿病SD大鼠主动脉炎症因子YKL-40表达,有助于减轻YKL-40在早期粥样硬化中的致病作用。

To investigate the effects of atorvastatin on expression of the pro-inflamma- tory cytokine, YKL-40, in the aortic intima of diabetic rats fed with an atherogenic diet. METHODS： Male Sprague-Dawley （SD） rats were randomly divided into five groups： control, atherogenic diet, atherogenic diet ＋ atorvasta tin, diabetes mellitus＋atherogenic diet, and di abetes mellitus ＋ atherogenic diet ＋ atorvasta tin （n=9, in each group）. Aortic atherosclero sis was induced by a single dose of vitamin D3, followed by a fatty diet. Diabetic model was es tablished using intraperitoneal injection of strep tozotocin （STZ）. Serum levels of fasting blood glucose （FBG）, HbAlc, triglyceride （TG） and total cholesterol （TC） were determined. The mRNA level and protein expression of YKL-40 in the aortic intima were measured after treat ment with atorvastatin （20 mg/kg） for 8 weeks. RESULTS：FBG, HbAlc, and TG were higher indiabetic rats with atherogenic diet than controls （all P^0.01） and rats with single atherogenic diet （all P%0.05）. Real-time PCR and immuno- histochemistry revealed that mRNA level and protein expression of YKL-40 were significantly elevated in the aortic intima of diabetic rats with atherogenic diet （all P % 0.01 vs controls and rats with single atherogenic diet）, which were significantly decreased after treatment with ator vastatin for 8 weeks （all P%0.01）. CONCLU- SION： Atorvastatin significantly suppresses aor tic YKL-40 expression in STZ-induced diabetic rats with atherogenic diet, suggesting that this agent may be beneficial in reducing the patholog ical effect of YKL-40 in the formation of athero sclerosis.