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

中国临床药理学与治疗学 ›› 2014, Vol. 19 ›› Issue (2): 133-138.

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

郑建雷¹, 陈秋静², 陆林², 张奇², 张瑞岩², 沈卫峰²

¹浙江省人民医院心内科,杭州 310014,浙江;
²上海交通大学医学院附属瑞金医院心内科,上海 200025

收稿日期:2013-06-14 修回日期:2014-02-17 出版日期:2014-02-26 发布日期:2014-03-31
通讯作者: 沈卫峰,男,博士,教授,研究方向:冠心病合并糖尿病的基础及临床研究。Tel: 021-64370045 E-mail: rjshenweifeng@yahoo.com.cn
作者简介:郑建雷,男,博士,主治医师,研究方向:冠心病的基础及介入研究。Tel: 0571-85893531,13675870102 E-mail: zhengjianlei@zjheart.com

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

ZHENG Jian-lei¹, CHEN Qiu-jing², LU Lin², ZHANG Qi², ZHANG Rui-yan², SHEN Wei-feng²

¹Department of Cardiology, Zhejiang Provincial People's Hospital, Hangzhou 310014, Zhejiang, China;
²Department of Cardiology, Rui Jin Hospital, Jiaotong University School of Medicine, Shanghai 200025, China

Received:2013-06-14 Revised:2014-02-17 Online:2014-02-26 Published:2014-03-31

摘要/Abstract

摘要： 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 (20 mg/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。

关键词: 阿托伐他汀, 高脂饮食, 糖尿病大鼠, YKL-40

Abstract: AIM: To investigate the effects of atorvastatin on expression of the pro-inflammatory 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 + atorvastatin, diabetes mellitus+atherogenic diet, and diabetes mellitus + atherogenic diet + atorvastatin (n=9, in each group). Aortic atherosclerosis was induced by a single dose of vitamin D3, followed by a fatty diet. Diabetic model was established using intraperitoneal injection of streptozotocin (STZ). Serum levels of fasting blood glucose (FBG), HbA1c, triglyceride (TG) and total cholesterol (TC) were determined. The mRNA level and protein expression of YKL-40 in the aortic intima were measured after treatment with atorvastatin (20 mg/kg) for 8 weeks.RESULTS: FBG, HbA1c, and TG were higher in diabetic rats with atherogenic diet than controls (all P<0.01) and rats with single atherogenic diet (all P<0.05). Real-time PCR and immunohistochemistry 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 atorvastatin for 8 weeks (all P<0.01).CONCLUSION: Atorvastatin significantly suppresses aortic YKL-40 expression in STZ-induced diabetic rats with atherogenic diet, suggesting that this agent may be beneficial in reducing the pathological effect of YKL-40 in the formation of atherosclerosis.

Key words: atorvastatin, atherogenic diet, diabetic rat, YKL-40

中图分类号:

R965.2

郑建雷, 陈秋静, 陆林, 张奇, 张瑞岩, 沈卫峰. 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[J]. 中国临床药理学与治疗学, 2014, 19(2): 133-138.

ZHENG Jian-lei, CHEN Qiu-jing, LU Lin, ZHANG Qi, ZHANG Rui-yan, SHEN Wei-feng. Atorvastatin ameliorates aortic YKL-40 level in diabetic rats fed with an atherogenic diet[J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2014, 19(2): 133-138.

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