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鞣花酸对心肌肌钙蛋白-T、溶酶体酶和膜结合 ATP 酶的药效动力学:来自生化、细胞因子和体外研究的机制线索。

Pharmacodynamics of ellagic acid on cardiac troponin-T, lyosomal enzymes and membrane bound ATPases: mechanistic clues from biochemical, cytokine and in vitro studies.

机构信息

SASTRA University, Thirumalaisamudram, Thanjavur, Tamil Nadu, India.

出版信息

Chem Biol Interact. 2011 Sep 5;193(2):154-61. doi: 10.1016/j.cbi.2011.06.005. Epub 2011 Jul 5.

DOI:10.1016/j.cbi.2011.06.005
PMID:21762681
Abstract

The anti lipid peroxidative and antioxidant effects of ellagic acid against isoproterenol-induced myocardial infarcted rats were reported previously. This study was designed to evaluate the protective effects of ellagic acid on the levels of cardiac troponin-T, lysosomal enzymes, and membrane bound ATPases along with the role of pro inflammatory cytokine. Male albino Wistar rats were pretreated with ellagic acid (7.5 and 15 mg/kg body weight) daily for a period of 10 days. After the pretreatment period isoproterenol (100mg/kg) was subcutaneously injected to rats twice at an interval of 24h. The protective effects of pretreatment with ellagic acid were measured by biochemical analysis and reverse transcriptase polymerase chain reaction. Evidence of myocardial infarction in isoproterenol induced rats included significant increase in the serum level of cardiac troponin-T and decreased levels of creatine kinase and lactate dehydrogenase in heart tissue homogenate .The pretreatment with ellagic acid restored the levels of cardiac markers in the serum and heart tissue homogenates. The activities of lysosomal enzymes (β-d-glucuronidase, β-N-acetyl glucosaminidase, β-galactosidase, cathepsin-d and acid phosphatase) were increased significantly in the serum and heart tissue of isoproterenol-induced rats. The activity of Na(+)/K(+)ATPase declined while the activities of Ca(2+)ATPase and Mg(2+)ATPase were increased significantly in the heart of isoproterenol-induced rats. Pretreatment with ellagic acid restored the activities of lysosomal enzymes and membrane bound ATPases. The higher expressions of pro-inflammatory cytokines such as interleukin-1β, interleukin-6 and tumour necrosis factor-α in the isoproterenol-induced rats were controlled by the pretreatment with ellagic acid. Our results imply that oral pretreatment with ellagic acid protects the heart lysosomal membrane against isoproterenol-induced cardiac damage. The observed effects might be due to the free radical scavenging, membrane stabilizing and anti-inflammatory properties of ellagic acid.

摘要

先前已有研究报道,鞣花酸具有抗脂质过氧化和抗氧化作用,可以对抗异丙肾上腺素诱导的心肌梗死大鼠。本研究旨在评估鞣花酸对心肌肌钙蛋白-T、溶酶体酶和膜结合 ATP 酶水平的保护作用,以及其在促炎细胞因子中的作用。雄性白化 Wistar 大鼠每天用鞣花酸(7.5 和 15mg/kg 体重)预处理 10 天。预处理期结束后,异丙肾上腺素(100mg/kg)在 24h 间隔内两次皮下注射至大鼠。用生化分析和逆转录聚合酶链反应测量鞣花酸预处理的保护作用。异丙肾上腺素诱导的大鼠心肌梗死的证据包括血清中心肌肌钙蛋白-T 水平显著升高,心脏组织匀浆中肌酸激酶和乳酸脱氢酶水平降低。鞣花酸预处理恢复了血清和心脏组织匀浆中心脏标志物的水平。溶酶体酶(β-d-葡糖醛酸酶、β-N-乙酰氨基葡萄糖苷酶、β-半乳糖苷酶、组织蛋白酶-D 和酸性磷酸酶)的活性在异丙肾上腺素诱导的大鼠血清和心脏组织中显著增加。Na(+)/K(+)ATPase 的活性降低,而 Ca(2+)ATPase 和 Mg(2+)ATPase 的活性在异丙肾上腺素诱导的大鼠心脏中显著增加。鞣花酸预处理恢复了溶酶体酶和膜结合 ATP 酶的活性。鞣花酸预处理可控制异丙肾上腺素诱导的大鼠中促炎细胞因子(如白细胞介素-1β、白细胞介素-6 和肿瘤坏死因子-α)的高表达。我们的结果表明,口服鞣花酸预处理可保护心脏溶酶体膜免受异丙肾上腺素引起的心脏损伤。观察到的作用可能归因于鞣花酸的自由基清除、膜稳定和抗炎特性。

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