3-Hydroxy-3-methylglutaryl coenzyme A reductase inhibitors prevent the development of cardiac hypertrophy and heart failure in rats.
3-Hydroxy-3-methylglutaryl coenzyme A reductase inhibitors prevent the development of cardiac hypertrophy and heart failure in rats.
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DOI：
10.1016/s0022-2828(03)00180-9
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发表时间：
2003-08
影响因子：
5
通讯作者：
H. Hasegawa;R. Yamamoto;H. Takano;M. Mizukami;M. Asakawa;T. Nagai;I. Komuro
中科院分区：
文献类型：
--
作者：
H. Hasegawa;R. Yamamoto;H. Takano;M. Mizukami;M. Asakawa;T. Nagai;I. Komuro
目标。-本研究的目的是确定3-羟基-3-甲基戊二酰辅酶A还原酶抑制剂(他汀类)是否对心肌肥厚和心力衰竭的发展具有预防作用。背景资料。-据报道，他汀类药物具有多种多效性，如抑制炎症和细胞增殖。方法：研究方法。将Dahl大鼠分为三组：LS组，低盐饮食组(0.3%氯化钠)；HS组，6周龄开始高盐饮食(8%氯化钠)；CERI组，6周龄开始灌胃高盐饮食，1 mg/kg/d。-在HS大鼠中，心功能明显受损，所有大鼠在17周内都表现出心力衰竭的迹象。CERI组大鼠的心功能优于HS组，17周龄前无一只死亡。与HS大鼠比较，HS大鼠心肌肥厚和纤维化程度减轻，心肌细胞凋亡细胞数减少，促炎症细胞因子IL-1β基因表达减少。西立伐他汀可抑制阿霉素诱导的新生大鼠心肌细胞凋亡。结论。-这些结果表明，他汀类药物对心肌细胞具有保护作用，可能有助于预防高血压心力衰竭的发展。
Objectives. – The aim of the present study was to determine whether 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors (statins) have preventive effects on the development of cardiac hypertrophy and heart failure. Background. – Statins have been reported to have various pleiotropic effects, such as inhibition of inflammation and cell proliferation. Methods. – Dahl rats were divided into three groups: LS, the rats fed the low-salt diet (0.3% NaCl); HS, the rats fed the high-salt diet (8% NaCl) from the age of 6 weeks; and CERI, the rats fed the high-salt diet with cerivastatin 1 mg/kg/d by gavage from the age of 6 weeks Results. – In HS rats, cardiac function was markedly impaired and all rats showed the signs of heart failure within 17 weeks of age. In CERI rats, cardiac function was better than that of HS and no rats were dead up to 17 weeks of age. The development of cardiac hypertrophy and fibrosis was attenuated, and the number of apoptotic cells and expression of proinflammatory cytokine interleukin (IL)-1β gene were less as compared with HS rats. Pretreatment of cerivastatin suppressed the adriamycin-induced apoptosis of cultured cardiomyocytes of neonatal rats. Conclusions. – These results suggest that statins have a protective effect on cardiac myocytes and may be useful to prevent the development of hypertensive heart failure.