Antioxidant enzyme gene expression in congestive heart failure following myocardial infarction
Antioxidant enzyme gene expression in congestive heart failure following myocardial infarction
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DOI：
10.1023/a:1025448908694
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发表时间：
2003-09-01
影响因子：
4.3
通讯作者：
Singal, PK
中科院分区：
文献类型：
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作者：
Khaper, N;Kaur, K;Singal, PK
氧化应激的增加和抗氧化酶的减少被认为参与了心肌梗死（MI）后充血性心力衰竭的病理生理过程。本研究的目的是表征在充血性心力衰竭大鼠后遗症的酶抗氧化剂，超氧化物歧化酶（SOD），谷胱甘肽过氧化物酶（GSHPx）和过氧化氢酶的mRNA丰度和蛋白质水平的变化。通过结扎左冠状动脉制备MI模型，并对对照组和PMI 1、4和16周组的心脏进行分析。氯沙坦治疗（2毫克/毫升的饮用水，每天）开始在4周，并持续12周。SOD mRNA水平在PMI 1周时下降约40%，PMI 4周时接近对照水平，PMI 16周时下降约73%，低于对照水平。GSHPx mRNA水平在所有时间点均保持不变。与对照组相比，过氧化氢酶的mRNA水平在1周和4周PMI时保持不变，在16周PMI时显著降低约44%。在1周和16周时，治疗和未治疗PMI组的MnSOD、CuZnSOD、GSHPx蛋白水平保持不变。然而，过氧化氢酶的蛋白水平在对照组和用氯沙坦处理的PMI组中显著增加。它的结论是，在严重心力衰竭过程中的SOD和过氧化氢酶活性的变化与这些酶的mRNA的变化。目前尚不清楚氯沙坦治疗后抗氧化储备和蛋白质水平改善的确切机制。
Increased oxidative stress and reduction in antioxidant enzymes have been suggested to be involved in the pathophysiology of congestive heart failure subsequent to myocardial infarction (MI). The objective of the present study was to characterize changes in the mRNA abundance and protein levels for the enzymatic antioxidants, superoxide dismutase ( SOD), glutathione peroxidase (GSHPx) and catalase during the sequelae of congestive heart failure in rats. MI was produced by the ligation of the left coronary artery and hearts from controls and 1, 4 and 16 week PMI groups were analyzed. Losartan treatment (2 mg/ml in drinking water, daily) was started at 4 weeks and continued for 12 weeks. The mRNA levels for SOD were reduced by about 40% at 1-week PMI, were near to the control levels at 4-week PMI and at 16 weeks PMI, the levels were reduced by about 73% below the controls. GSHPx mRNA levels remained unchanged at all time points. The mRNA levels for catalase remained unchanged at 1 and 4 weeks PMI and were significantly reduced by about 44% at 16 weeks PMI as compared to the controls. The protein levels for MnSOD, CuZnSOD, GSHPx at 1 and 16 weeks remained unchanged in treated and untreated PMI groups. However, the protein levels for catalase was significantly increased in the control and PMI groups treated with Losartan. It is concluded that changes in the SOD and catalase activities during severe heart failure correlated with changes in mRNA for these enzymes. The precise mechanism/s for the improvement in antioxidant reserve and protein levels after Losartan treatment is/are unclear at this time.