·糖尿病基础研究·

      【摘要】 目的 观察AGE诱导心肌成纤维细胞氧化应激(OS)和胶原蛋白Ⅰ、Ⅲ合成分泌的影响及罗格列酮(RGZ)的干预作用。 方法 不同浓度AGE与心肌成纤维细胞孵育，予RGZ干预48 h，收集培养上清液，分别应用超氧化物歧化酶(SOD)、丙二醛(MDA)试剂盒检测SOD活性和MDA含量，采用ELISA检测胶原蛋白Ⅰ、Ⅲ含量。 结果 RGZ与200 mg/L AGE共同孵育心肌成纤维细胞48 h，随RGZ浓度增高(0.1、1、10 mol/L)，心肌成纤维细胞培养上清液中SOD活性逐渐增高[(21.564±1.614)，(22.323±1.260)，(23.661±1.562) vs (19.320±0.896) nU/ ml，P<0.05或P<0.01];与200 mg/L AGE组比较，MDA含量逐渐降低[(1.325±0.048)，(1.279±0.032)，(1.229±0.045)vs(1.629±0.043) nmol/ml，P<0.01];与200 mg/L AGE组比较，胶原蛋白Ⅰ和胶原蛋白Ⅲ含量均呈递减趋势[(79.17±3.25)，(60.42±3.58)，(42.71±5.11)vs(85.54±2.28) ng/ml,P<0.01;(37.52±3.43)，(27.09±4.75)，(20.81±3.26) vs (40.75±2.70) ng/ml,P<0.01]。 结论 AGE诱导心肌成纤维细胞OS，增加胶原蛋白Ⅰ、Ⅲ合成分泌;RGZ能抑制AGE诱导的心肌成纤维细胞OS，抑制AGE诱导的胶原蛋白Ⅰ、Ⅲ合成分泌，对糖尿病心肌纤维化的防治有重要意义。

　　【关键词】 罗格列酮;糖基化终产物;心肌成纤维细胞;胶原蛋白;氧化应激

　　Effect of rosiglitazone on oxidative stress and collagen metabolism in rat cardiac fibroblasts induced by advanced glycation end products LI Jie, LIU Nai-feng, REN Li-qun. Department of Geriatrics, Zhongda Hospital, Southeast University, Nanjing 210009, China

　　Corresponding author：LIU Nai-feng, E-mail：liunf@seu.edu.com

　　【Abstract】 Objective To investigate induction effect of AGE on oxidative stress and type Ⅰ, Ⅲ collagen synthesis in rat cardiac fibroblasts and interference effect of RGZ during the course. Methods Incubate rat cardiac fibroblasts with AGE of different concentration, add RGZ to interfere for 48 h, and then collect supernatant fluid, superoxide dismutase (SOD) activity and malondialdehyde (MDA) content were detected by SOD kit and MDA kit separately and type Ⅰ, Ⅲ collagen contents were measured by ELISA. Results When incubating cardiac fibroblasts with RGZ and 200 mg/L AGE together for 48 h, with the rise of RGZ concentration(0.1,1 and 10mol/L),SOD activity in the supernatant fluid of cultured cardiac fibroblasts gradually increased[(21.564±1.614),(22.323±1.260),(23.661±1.562)vs (19.320±0.896) nU/ml, P<0.05 or P<0.01], MDA content gradually decreased [(1.325±0.048), (1.279±0.032), (1.229±0.045) vs (1.629±0.043) nmol/ml, P<0.01] and type Ⅰ, Ⅲ collagen Contents gradually decreased[(79.17±3.25), (60.42±3.58), (42.71±5.11) vs (85.54±2.28) ng/ml, P<0.01;(37.52±3.43)，(27.09±4.75)，(20.81±3.26) vs (40.75±2.70) ng/ml, P<0.01] as compared with 200 mg/L AGE group. Conclusion AGE can induce oxidative stress in cardiac fibroblasts and increase type Ⅰ, Ⅲ collagen contents; RGZ can inhibit oxidative stress in cardiac fibroblasts and synthesis and secretion of type Ⅰ, Ⅲ collagen induced by AGE. This finding indicates that RGZ may play an important role in prevention of diabetic myocardial fibrosis.

　　【Key words】 Rosiglitazone (RGZ);Advanced glycation end products (AGE);Cardiac fibroblasts;Collagen;Oxidative stress (OS)