Department of Medical Biochemistry, Faculty of Medicine, Cairo University, Cairo, Egypt.
J Cardiovasc Pharmacol. 2010 Mar;55(3):262-8. doi: 10.1097/FJC.0b013e3181cf91ac.
The present study was designed to compare the cardioprotective effects of the combination of lisinopril with growth hormone over lisinopril alone in doxorubicin (Dox)-induced cardiomyopathy in rats. Forty male Wister albino rats were divided into 4 groups: group 1, control group; group 2, received Dox; group 3, received lisinopril + Dox; and group 4, received lisinopril + Dox + growth hormone. Dox (cumulative dose) was administered to rats in 6 equal intraperitoneal injections over a period of 2 weeks. Histopathological changes and plasma aspartate aminotransferase, lactate dehydrogenase, and creatine kinase and plasma levels of matrix metalloproteinase (MMP)-2, tissue inhibitor matrix metalloproteinase (TIMP)-1, and cardiac inducible nitric oxide synthase (iNOS) messenger RNA (mRNA) expression were determined 9 weeks after the first dose of Dox. Dox produced cardiac structural injury and significant elevation in plasma levels of cardiac enzymes, MMP-2, and cardiac iNOS mRNA expression together with significant reduction in plasma TIMP-1 level. Lisinopril significantly decreases plasma MMP-2 level and cardiac iNOS mRNA expression by 13% and 15%, respectively, in group 3 compared with 36% and 47%, respectively, in group 4 as compared with group 2. In addition, compared with Dox group, lisinopril significantly increases plasma TIMP-1 level by 23% compared with 49% in group 4. We can conclude that the combination of lisinopril and growth hormone produced better cardioprotective effect against Dox-induced cardiomyopathy. This effect may be attributed on their antiremodeling actions by regulating plasma MMP-2/TIMP-1 levels and to the reduction of cardiac iNOS mRNA expression.
本研究旨在比较赖诺普利联合生长激素与单纯赖诺普利对阿霉素（Dox）诱导的大鼠心肌病的心脏保护作用。将 40 只雄性 Wister 白化大鼠分为 4 组：第 1 组，对照组；第 2 组，给予 Dox；第 3 组，给予赖诺普利+Dox；第 4 组，给予赖诺普利+Dox+生长激素。Dox（累积剂量）以 6 次腹腔注射的方式在 2 周内给予大鼠。首次给予 Dox 9 周后，测定组织病理学变化以及血浆天冬氨酸转氨酶、乳酸脱氢酶和肌酸激酶水平和血浆基质金属蛋白酶（MMP）-2、基质金属蛋白酶组织抑制剂（TIMP）-1和心脏诱导型一氧化氮合酶（iNOS）信使 RNA（mRNA）表达水平。Dox 导致心脏结构损伤，并显著升高血浆中心脏酶、MMP-2 和心脏 iNOS mRNA 表达水平，同时显著降低血浆 TIMP-1 水平。与第 2 组相比，第 3 组赖诺普利可使 MMP-2 水平分别降低 13%和 iNOS mRNA 表达分别降低 15%，与第 4 组相比分别降低 36%和 47%。此外，与 Dox 组相比，赖诺普利可使 TIMP-1 水平分别增加 23%和 49%。我们可以得出结论，赖诺普利联合生长激素对 Dox 诱导的心肌病具有更好的心脏保护作用。这种作用可能归因于它们通过调节血浆 MMP-2/TIMP-1 水平和降低心脏 iNOS mRNA 表达的抗重构作用。
