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首页> 外文期刊>Bulletin of the National Research Centre >Effect of the New Anti- Ischaemic Drug 'Trimetazidine' on Hepatic Injury Caused by Carbon Tetrachloride in Rats
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Effect of the New Anti- Ischaemic Drug 'Trimetazidine' on Hepatic Injury Caused by Carbon Tetrachloride in Rats

机译：新型抗缺血药物“三甲嗪”对四氯化碳致大鼠肝损伤的影响

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The effects of trimetazidine, a novel anti-ischaemic agent, on the development of hepatic injury induced in rats with carbon tetrachloride, were investigated. Hepatotoxicity was induced by CCl_4 orally (0.2 ml/kg followed by 0.1 ml/kg after one week). Trimetazidine at three dose levels (3.6, 7.2 and 14.4 mg/kg), silymarin (25 mg/kg) and combination of trimetazidine (7.2 mg/kg) and silymarin (25 mg/kg) were administered orally daily for 15 days, starting at time of administration of CCl_4. The daily administration of trimetazidine conferred significant protection against the hepatotoxic effects of CCl_4 in rats. It decreased the increases in serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), and alkaline phosphatase (ALP) and also prevented the development of hepatic necrosis caused by CCl_4 as determined 15 days after drug administration. Thus, compared with the CCl_4 control group, serum ALT decreased by 35.1, 49.5 and 57%, AST by 28.2, 31.6 and 36% and ALP by 32, 39.7 and 40.6%, after the administration of trimetazidine at 3.6, 7.2 and 14.4 mg/kg, respectively. Silymarin administered alone, at the dose of 25 mg/kg reduced serum ALT by 30%, AST by 29.1% and ALP by 38.4% compared to CCl_4 control. When silymarin was combined with 7.2 mg/kg of trimetazidine, the activities of ALT, AST and ALP were markedly decreased by 47.2%, 47.2% and 50.6%, respectively, compared with the CCl_4 control, indicating a beneficial additive effect. Histopathologic examination of the liver of rats treated with CCl_4 + trimetazidine showed less fibrosis compared with the CCl_4-control group. Cotreatment with silymarin and trimetazidine, on the other hand resulted in marked histologic protection. It is concluded that the anti-ischaemic agent trimetazidine lessened hepatocellular injury caused by CCl_4 in rats, and had additive effect with silymarin. It was suggested, therefore, that trimetazidine alone or in combination with silymarin might have a place in the therapy of chronic liver diseases.
机译：研究了一种新型抗缺血药物曲美他嗪对四氯化碳大鼠肝损伤发展的影响。口服CCl_4诱导肝毒性（0.2 ml / kg，一周后0.1 ml / kg）。从开始开始，每天口服15天的三种剂量的Trimetazidine（3.6、7.2和14.4 mg / kg），水飞蓟素（25 mg / kg）以及曲美他嗪（7.2 mg / kg）和水飞蓟素（25 mg / kg）的组合在给予CCl_4时。曲美他嗪的每日给药对大鼠的CCl_4的肝毒性作用具有明显的保护作用。给药15天后，它降低了血清丙氨酸转氨酶（ALT），天冬氨酸转氨酶（AST）和碱性磷酸酶（ALP）的增加，并防止了由CCl_4引起的肝坏死的发展。因此，与曲美他嗪3.6、7.2和14.4 mg相比，与CCl_4对照组相比，血清ALT降低了35.1、49.5和57％，AST降低了28.2、31.6和36％，ALP降低了32、39.7和40.6％。 / kg。与CCl_4对照相比，单独以25 mg / kg的剂量施用水飞蓟素可使血清ALT降低30％，AST降低29.1％，ALP降低38.4％。水飞蓟素与7.2 mg / kg曲美他嗪组合使用时，与CCl_4对照相比，ALT，AST和ALP的活性分别显着降低47.2％，47.2％和50.6％，表明具有有益的累加作用。与CCl_4对照组相比，用CCl_4 +曲美他嗪治疗的大鼠肝脏的组织病理学检查显示较少的纤维化。另一方面，与水飞蓟素和曲美他嗪的共同治疗导致明显的组织学保护。结论：抗缺血药物曲美他嗪减轻了大鼠CCl_4引起的肝细胞损伤，对水飞蓟素具有累加作用。因此，建议单独使用曲美他嗪或与水飞蓟素联合使用可能在慢性肝病的治疗中占有一席之地。

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