曲美他嗪降低1型糖尿病大鼠心肌组织炎症反应和氧化应激水平

Trimetazidine suppresses Inflammatory Response and Oxidative Stress in Cardiac Tissue of Type 1 Diabetic Rats

【目的】探讨曲美他嗪对链佐菌素诱导的1型糖尿病大鼠心肌组织肿瘤坏死因子-α(TNF-α)和超氧化物歧化酶-2(SOD-2)蛋白表达、心肌组织氧化应激水平及心脏功能的影响。【方法】选用6周龄雄性SD大鼠30只,随机分为3组:正常对照组(N组);糖尿病对照组(10只,C组);糖尿病联合曲美他嗪干预组(TMZ:15 mg·kg-1·d-1;N=10,TMZ组)。将链佐菌素溶解于0.1 mol/L柠檬酸缓冲液中,以40 mg·kg-1剂量腹腔注射大鼠,诱导1型糖尿病大鼠模型。TMZ组以曲美他嗪(15 mg·kg-1·d-1)灌胃,持续16周。16周后采用彩色多普勒超声及颈动脉导管检测大鼠心功能及血流动力学指标,Western blot技术及试剂盒检测TNF-α和SOD 2蛋白表达及丙二醛(MDA)水平,称量身体质量(BW)、大鼠左室质量(LVW)、全心质量(HW),HE染色观察心肌组织形态。【结果】与N组相比,C组心脏功能降低;LVW/HW及MDA增高(P<0.05),而SOD-2表达降低(P<0.001)。与C组比较,TMZ组TNF-α、MDA、LVEDP和LVW/HW降低,SOD 2升高(P<0.05)。曲美他嗪治疗组心肌组织病理形态改变较糖尿病对照组减轻。【结论】心肌组织TNF-α表达上调和氧化应激水平升高在糖尿病发生发展中可能起重要作用。曲美他嗪可降低炎症因子TNF-α表达、改善氧化应激损伤、减缓心肌重塑和改善心脏舒张功能。

[ Objective ] To investigate the effect of trimetazidine （TMZ） on oxidative stress level, expressions of TNF-α and SOD- 2 from myocardial tissue and cardiac function in the rats with type-1 diabetes induced by streptozotocin. [Methods] Thirty male Sprague-Dawley （SD） rats were randomly subdivided into three groups： Group N consisted of nominal rats （normal control group, n = 10）. Group C consisted of diabetic rats （diabetic controls, n = 10）. Diabetes was induced by a single intraperitoneal injection of STZ at 40 mg/kg body weight in 0.1 M citrate buffered saline.Group TMZ consisted of diabetic rats （n =10） received TMZ （15 mg·kg-1·d-1） orally by gavage for 16 weeks. At 16 weeks, the final body weight（BW）,heart weight（HW）, and left ventricle weight（LVW） were recorded. And cardiac function and hemodynamic index were assessed by color doppler ultrasound and miniature pressure transducer （Millar Micro-Tip） respectivly. We also measured MDA level and the expressions of TNF-α and SOD-2 in the myocardial tissue and observed the myocardial morphology by HE staining. [Results] Compared with group N, LYW/HW, LVW/BW and MDA rose and the cardiac function decreased in group C （P 〈 0.05）. There were lower protein expression of SOD-2 （P 〈 0.001）and higher protein expressions of TNF-α in group C than group N （P 〈 0.05）. TMZ treatment successfully up-regulated the SOD-2 expression （P 〈0.05）, down-regulated the expression of TNF-ct （P 〈 0.05）, and reduced MDA level, LVEDP and LVW/HW （P 〈 0.05）. [ Conclusion ] The increase of TNF-α protein expression and oxidative stress level may play important roles in the occurrence and development of diabetic cardiomyopathy.Trimetazidine may reduce the protein expression of TNF-a, decrease oxidative stress level and improve cardiac diastolic function.