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阿霉素处理大鼠心脏、肝脏和肾脏组织炎症变化的生化评估及外源性肝素衍生物治疗的调节作用

Biochemical evaluation of the inflammatory changes in cardiac, hepatic and renal tissues of adriamycin-administered rats and the modulatory role of exogenous heparin-derivative treatment.

作者信息

Deepa P R, Varalakshmi P

机构信息

Department of Medical Biochemistry, Dr. ALM Post Graduate Institute of Basic Medical Sciences, University of Madras, Taramani, Chennai 600113, India.

出版信息

Chem Biol Interact. 2005 Oct 20;156(2-3):93-100. doi: 10.1016/j.cbi.2005.07.008.

Abstract

The aim of the present work is to evaluate the role of a heparin derivative, low molecular weight heparin (LMWH), certoparin on the inflammatory changes in adriamycin (ADR) cytotoxicity on a biochemical basis. Male Wistar rats (140+/-10g) were divided into four groups: untreated control, ADR group (a single dose intravenous injection of 7.5 mg/kg ADR), LMWH control (300 microg/(day rat) s.c. for 1 week) and ADR plus LMWH group (7.5 mg/kg ADR on day 1 of study period followed by LMWH treatment, 300 microg/(day rat) commencing on day 8 and continued for 1 week). At the end of the 2-week experimental period, biochemical assessment of the inflammatory status was carried out in the plasma, cardiac, hepatic and renal tissues. Increased concentrations of plasma C-reactive protein (CRP) and fibrinogen indicated severe inflammation in the ADR cytotoxic rats. These acute-phase inflammatory markers diminished significantly in the LMWH treated group, when compared with the cytotoxic group (p<0.001). Tissue damage was marked by elevated levels of plasma and tissue hexose, hexosamine, hexuronic acid and sialic acid, which were reversed on LMWH administration (p<0.001). The activities of lysosomal enzymes was measured in the experimental groups, and it was observed that the ADR induced rats showed a marked increase in the enzymic activities, while LMWH treated rats revealed normal activities. The present study throws light on the inflammatory changes in the ADR-challenged heart, liver and kidney tissues, and projects the biochemical basis for the anti-inflammatory property of the LMWH, certoparin.

摘要

本研究的目的是从生化角度评估一种肝素衍生物——低分子量肝素(LMWH)、舍托肝素对阿霉素(ADR)细胞毒性炎症变化的作用。雄性Wistar大鼠(140±10g)分为四组:未处理对照组、ADR组(单次静脉注射7.5mg/kg ADR)、LMWH对照组(皮下注射300μg/(天·只大鼠),持续1周)和ADR加LMWH组(在研究期第1天注射7.5mg/kg ADR,随后从第8天开始进行LMWH治疗,300μg/(天·只大鼠),持续1周)。在2周实验期结束时,对血浆、心脏、肝脏和肾脏组织进行炎症状态的生化评估。血浆C反应蛋白(CRP)和纤维蛋白原浓度升高表明ADR细胞毒性大鼠存在严重炎症。与细胞毒性组相比,LMWH治疗组这些急性期炎症标志物显著降低(p<0.001)。血浆和组织中己糖、氨基己糖、己糖醛酸和唾液酸水平升高表明组织损伤,而给予LMWH后这些指标恢复正常(p<0.001)。在实验组中测量了溶酶体酶的活性,观察到ADR诱导的大鼠酶活性显著增加,而LMWH治疗的大鼠酶活性正常。本研究揭示了ADR攻击的心脏、肝脏和肾脏组织中的炎症变化,并揭示了LMWH舍托肝素抗炎特性的生化基础。

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