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首页> 外文期刊>European journal of pharmaceutical sciences >Curcumin prevents diabetic cardiomyopathy in streptozotocin-induced diabetic rats: Possible involvement of PKC-MAPK signaling pathway
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Curcumin prevents diabetic cardiomyopathy in streptozotocin-induced diabetic rats: Possible involvement of PKC-MAPK signaling pathway

机译：姜黄素预防链脲佐菌素诱导的糖尿病大鼠的糖尿病心肌病：PKC-MAPK信号通路的可能参与

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The development of diabetic cardiomyopathy is accompanied with a high membrane-bound protein kinase C (PKC) levels. Curcumin is a naturally occurring compound which is known to inhibit PKC activity. However, the effects of curcumin on ameliorating diabetic cardiomyopathy are still undefined. We evaluated whether curcumin treatment is associated with the modulation of PKC-α and -β 2-mitogen-activated protein kinase (MAPK) pathway in experimental diabetic cardiomyopathy. Diabetes was induced in male Sprague-Dawley rats by streptozotocin (STZ). Curcumin (100 mg/kg/day) was started three weeks after STZ injection and was given for 8 weeks. We demonstrate that curcumin significantly prevented diabetes-induced translocation of PKC-α and -β2 to membranous fraction and diabetes-induced increased phosphorylation of p38MAPK and extracellular regulated-signal kinase (ERK)1/2 in left ventricular tissues of diabetic rats. Curcumin treatment also markedly decreased NAD(P)H oxidase subunits (p67phox, p22phox, gp91phox), growth factors (transforming growth factor-β, osteopontin) and myocyte enhancer factor-2 protein expression as well as inhibited NF-κB activity at nuclear level. Furthermore, curcumin decreased the mRNA expression of transcriptional coactivator p300 and atrial natriuretic peptide, decreased accumulation of ECM protein and reversed the increment of superoxide production in left ventricular tissues, as evidenced by dihydroethidium staining. It is also significantly lowered plasma glucose and attenuated oxidative stress, as determined by lipid peroxidation and activity of anti-oxidant enzyme, and as a result attenuated cardiomyocyte hypertrophy, myocardial fibrosis and left ventricular dysfunction. Taken together, it is suggested that curcumin by inhibiting PKC-α and -β 2-MAPK pathway may be useful as an adjuvant therapy for the prevention of diabetic cardiomyopathy.
机译：糖尿病性心肌病的发展伴随着高的膜结合蛋白激酶C（PKC）水平。姜黄素是一种天然存在的化合物，已知可以抑制PKC活性。然而，姜黄素对改善糖尿病性心肌病的作用仍不确定。我们评估了姜黄素治疗是否与糖尿病性心肌病中PKC-α和-β2丝裂原活化蛋白激酶（MAPK）通路的调节有关。链脲佐菌素（STZ）在雄性Sprague-Dawley大鼠中诱发糖尿病。姜黄素（100 mg / kg /天）在STZ注射后三周开始服用，持续8周。我们证明姜黄素可显着预防糖尿病诱导的糖尿病大鼠左心室组织中PKC-α和-β2向膜部分的转运，以及糖尿病引起的p38MAPK和细胞外调节信号激酶（ERK）1/2磷酸化的增加。姜黄素治疗还显着降低NAD（P）H氧化酶亚基（p67phox，p22phox，gp91phox），生长因子（转化生长因子-β，骨桥蛋白）和肌细胞增强因子2蛋白的表达，并抑制核水平的NF-κB活性。 。此外，姜黄素降低了转录共激活因子p300和心钠素的mRNA表达，降低了ECM蛋白的积累，并逆转了左心室组织中超氧化物生成的增加，这是通过二氢乙啶染色证明的。如脂质过氧化作用和抗氧化酶的活性所确定的，它还可以显着降低血浆葡萄糖和减轻氧化应激，从而减轻心肌肥大，心肌纤维化和左心功能不全。两者合计，提示通过抑制PKC-α和-β2 -MAPK途径的姜黄素可以用作预防糖尿病性心肌病的辅助疗法。

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