中文摘要：

本研究旨在观察2型糖尿病大鼠心肌损伤时硫氧还蛋白（thioredoxin,Trx）系统在心肌组织中的活性变化,并探讨其机制。成年Sprague Dawley大鼠随机分为2组：糖尿病组给予高糖、高脂饮食,并且腹腔注射链唑霉素（streptozocin,STZ）造成大鼠2型糖尿病模型;对照组普通饲料喂养,腹腔注射柠檬酸缓冲液。在注射STZ后不同时间点,测定大鼠血糖浓度和血清胰岛素、肌酸激酶同工酶（creatine kinase MB,CK-MB）、心肌肌钙蛋白I（cardiac troponin I,cTnI）浓度,测定心肌Trx活性、Trx还原酶（thioredoxin reductase,TR）活性和caspase-3活性,用real time PCR和Western blot测定心肌Trx1、Trx2、TR1、TR2和Trx相关蛋白（thioredoxin interacting protein,TXNIP）的mRNA和蛋白表达。结果显示,注射STZ后第1周,2型糖尿病大鼠模型建立成功;注射STZ后第2周即可诱发心肌损伤,第4周上调caspase-3活性。糖尿病组大鼠心肌Trx和TR活性在注射STZ后第2周显著降低,并随病程呈进行性下降;糖尿病组大鼠心肌Trx1、Trx2、TR1、TR2的mRNA水平均在注射STZ后第4周显著下降,而在第12周时则明显升高;Western blot结果显示糖尿病组大鼠心肌Trx、TR、TXNIP蛋白表达在注射STZ后第12周时均显著升高。以上结果表明,2型糖尿病大鼠心肌损伤时Trx和TR活性受抑,而Trx、TR的mRNA表达受到抑制后,代偿性增多,TXNIP的表达明显上调,Trx系统蛋白表达均明显上调,提示Trx系统活性下降的主要原因可能是抑制性蛋白表达升高和化学修饰。

英文摘要：

The aim of the present study is to investigate the change of thioredoxin （Trx） system in myocardial tissue of type 2 diabetic rats after myocardial injury and the underlying mechanism. Adult Sprague Dawley rats were randomly divided into two groups： normal control （NC） group and diabetes （DM） group. Rats in DM group were subjected to high-sugar, high-fat diet and streptozotocin （STZ） injection. Rats in NC group were only given normal diet and equal amount of citric acid buffer injection. At week 1, 2, 4, 12, 21 after STZ injection, plasma glucose concentration and the concentrations of insulin, creatine kinase MB （CK-MB）, cardiac troponin I （cTnI） in serum were measured. Myocardial Trx and thioredoxin reductase （TR） activities, as well as caspase-3 activity, were determined by respective assay methods. Protein and mRNA levels of Trx, TR, Trx interacting protein （TXNIP） were determined by Western blot and real time PCR, respectively. The results showed that type 2 diabetic rat model was successfully established at week 1 after STZ injection, and myocardial injury was induced from week 2. Moreover, caspase-3 activity was significantly increased at week 4, 12 indiabetic rats. The activities of myocardial Trx and TR in diabetic rats was decreased from week 2, and continually aggravated as the disease developed. Compared with those in NC group, the mRNA levels of Trx1, Trx2, TR1, TR2 in DM group decreased at week 4, and then increased in week 12. In DM group, the protein levels of Trx1, Trx2, TR1 and TR2 increased significantly at week 12. The mRNA expressions of myocardial TXNIP in diabetic rats were significantly increased at week 4, 12, 24 and protein expression was increased at week 12. These results suggest diabetes can decrease myocardial Trx, TR activity, inducing myocardial cell apoptosis and heart injury. The inhibitory effect of diabetes is mainly associated with TXNIP up-regulation and Trx nitration.