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缬沙坦预处理对乳鼠心肌细胞缺氧/复氧损伤的保护作用(1)
http://www.100md.com 2011年4月1日 王亮 戴振华 陈鹏
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     【摘要】目的:探讨缬沙坦预处理对乳鼠心肌细胞缺氧/复氧损伤的保护作用及其机制。方法:常规方法培养心肌细胞,培养72小时后,分为三组:正常对照组、心肌细胞缺氧/复氧损伤组、缬沙坦预处理后心肌细胞缺氧/复氧损伤组。分别观察心肌细胞结构,测定心肌细胞存活率、乳酸脱氢酶(LDH)、丙二醛(MDA)及超氧化物歧化酶(SOD)水平。结果:与对照组比心肌细胞缺氧/复氧损伤组细胞存活率明显下降、培养液中LDH、MDA含量明显增高,SOD含量明显下降;与心肌细胞缺氧/复氧损伤组比,缬沙坦预处理组心肌细胞存活率明显提高,培养液中LDH、MDA含量明显下降、SOD含量明显上升。结论 缬沙坦通过抗氧化、抗脂质过氧化反应,清除氧自由基对乳鼠心肌细胞缺氧/复氧损伤有保护作用。

    【关键词】缬沙坦;心肌细胞;缺氧复氧;预处理

    【中图分类号】R322.11;R541.4【文献标识码】A【文章编号】1008-6455(2011)08-0582-02

    Protective effects of Valsartan pretreatment on hypoxia/reoxygen injury in neonatal SD rat cardiomyocytes

    Wang Liang1 Dai Zhenhua2 Chen Peng3

    【Abstract】Objective:To observe protective action of Valsartan pretreatment on hypoxia/reoxygen injury in neonatal SD rat cardiomyocytes and to investigate the mechanism.Methods:To establish a model for primary culture of cardiomyocytes injuried by hypoxia/reoxygen. The morphology of cardiomyocytes was observed, and cardiomyocytes fraction surviving were measured, and the activity of lactate dehydrogenase (LDH), malondialdehyde (MDA), superoxide dismutase (SOD) were assayed.Results:Valsartan pretreatment on hypoxia/reoxygen injury in neonatal SD rat cardiomyocytesinhance cardiomyocytes fraction surviving (P<0.05), and decrease the activity of LDH, content of MDA and improve the acivity of SOD in the injuried myocytes (P<0.05). Conclusion:Valsartan pretreatment can prevent the cultured cardiac myocytes during hypoxia/reoxygenation injury obviously. The mechanisms may be as below: Valsartan pretreatment can stabilized the membrane of myocardium, restrict oxygen free radical injury in cardiac myocyte during hypoxia/reoxygenation injury.

    【Key words】Valsartan; cultured cardiac myocyte; hypoxia/reoxygenation injury; pretreatment

    大量实验显示心肌细胞缺氧/复氧损会引起心肌细胞损伤并引起心肌细胞缺失,在心脏病病理进程中扮演重要的角色[1]。目前已有研究证明,Ang lI受体拮抗剂缬沙坦通过选择性拮抗AT受体,激活AT受体及直接作用,产生抗缺血再灌注损伤心律失常,减少梗死面积,减轻心肌顿抑等多种心肌保护作用[2]。但缬沙坦对体外培养的心肌细胞缺氧/复氧损伤的影响尚未见报道。 我们通过乳鼠心肌细胞原代培养,建立心肌细胞缺氧/复氧损伤的模型,观察缬沙坦对心肌细胞缺氧/复氧损伤的保护作用,在细胞水平探讨它对心肌细胞缺氧/复氧损伤的保护作用和可能的机制。

    1 材料与方法

    1.1 实验动物 1~2 d龄SD大鼠,雌雄不拘,共260只。

    药品及主要试剂。药品:缬沙坦(瑞士原粉,诺华公司惠赠)。试剂:DMEM/F12(1∶1) 培养基(Hyclone公司,美国), 5-溴脱氧尿嘧啶(5-Brdu ......

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