Zhang Wei, Zhong Ming, Tang Meng-xiong, Ma Xiao, Miao Ya, Sun Hui, Zhang Yun
Department of Cardiology, Qilu Hospital of Shandong University, Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education and Public Health, Jinan 250012, China.
Zhonghua Xin Xue Guan Bing Za Zhi. 2006 Mar;34(3):212-6.
Tribbles, a protein family controlling mitogen-activated protein kinase cascades, might contribute to the remodeling process in dilated cardiomyopathy. We investigated the gene expression of Tribble 3 (TRB(3)), cardiac function and collagen changes in rats with diabetic cardiomyopathy (DCM) and the modulating effects of valsartan on them.
Male Wistar rats were fed with high cholesterol diet throughout the study period, streptozocin (30 mg/kg, i.p) was given at the 28th day, valsartan (30 mg.kg(-1).d(-1), n = 13) or placebo (n = 11) was administered at the 35th day to rats with fasting blood glucose > or = 11.1 mmol/L per gavage for another 12 weeks. Control rats (n = 8) were fed with regular chow. Fasting blood glucose was monitored throughout the study, left ventricular function was determined by echocardiography, myocardial collagen content quantified after Masson-staining and myocardial mRNA expression of TRB(3) detected by quantification real-time RT-PCR at the end of study.
Cardiac function was significantly improved (EF: 74% +/- 10% vs. 66% +/- 7%, P < 0.05), myocardial collagen content decreased (13.23 +/- 3.14 vs. 16.92 +/- 3.18, P < 0.05) in rats with DCM treated with valsartan. Moreover, TRB(3) mRNA was significantly increased in rats with DCM compared to control rats (0.0198 +/- 0.0082 vs. 0.1108 +/- 0.0933, P < 0.05) and the increase could be significantly attenuated by valsartan (0.0367 +/- 0.0234, P < 0.05 vs. DCM). A significant positive correlation was observed between myocardial TRB(3) mRNA and myocardial collagen content (r = 0.67, P < 0.05) and between TRB(3) mRNA and fasting blood glucose (r = 0.69, P < 0.05) in rats with DCM.
Our results show for the first time that myocardial TRB(3) mRNA is upregulated in rats with DCM and which could be down-regulated by valsartan.
Tribbles是一个控制丝裂原活化蛋白激酶级联反应的蛋白质家族，可能参与扩张型心肌病的重塑过程。我们研究了糖尿病心肌病（DCM）大鼠中Tribble 3（TRB(3)）的基因表达、心脏功能和胶原变化，以及缬沙坦对它们的调节作用。
在整个研究期间，雄性Wistar大鼠喂食高胆固醇饮食，在第28天腹腔注射链脲佐菌素（30 mg/kg），对空腹血糖≥11.1 mmol/L的大鼠在第35天通过灌胃给予缬沙坦（30 mg·kg(-1)·d(-1)，n = 13）或安慰剂（n = 11），持续12周。对照大鼠（n = 8）喂食常规饲料。在整个研究过程中监测空腹血糖，通过超声心动图测定左心室功能，在研究结束时通过Masson染色定量心肌胶原含量，并通过定量实时RT-PCR检测心肌TRB(3)的mRNA表达。
缬沙坦治疗的DCM大鼠心脏功能显著改善（射血分数：74%±10% vs. 66%±7%，P < 0.05），心肌胶原含量降低（13.23±3.14 vs. 16.92±3.18，P < 0.05）。此外，与对照大鼠相比，DCM大鼠的TRB(3) mRNA显著增加（0.0198±0.0082 vs. 0.1108±0.0933，P < 0.05），而缬沙坦可显著减弱这种增加（0.0367±0.0234，与DCM组相比P < 0.05）。在DCM大鼠中，心肌TRB(3) mRNA与心肌胶原含量之间（r = 0.67，P < 0.05）以及TRB(3) mRNA与空腹血糖之间（r = 0.69，P < 0.05）存在显著正相关。
我们的结果首次表明，DCM大鼠心肌TRB(3) mRNA上调，而缬沙坦可使其下调。
