依达拉奉通过SIRT1抑制小鼠阿霉素心肌损伤的作用研究

发布时间：2018-10-20 18:50

【摘要】：目的:探讨依达拉奉(EDA)对阿霉素致小鼠心肌损伤的保护作用。方法:以阿霉素3mg/kg腹腔注射,隔日1次,共7次致小鼠心肌损伤,造模同时开始以EDA低、高剂量(5、10mg/kg)连续2周腹腔注射。光镜下观察小鼠心室肌组织形态学变化;测定血清肌酸激酶(CK)和乳酸脱氢酶(LDH)活性;ELISA法测定反映心肌组织的炎性因子肿瘤坏死因子(TNF-α)和白细胞介素6(IL-6)的水平;比色法检测心肌组织中的超氧化物歧化酶(SOD)、丙二醛(MDA)和一氧化氮(NO)含量的变化;Western blot检测心肌组织中转化生长因子-β1(TGF-β1)和沉默信息调节因子2的哺乳动物同源体1(SIRT1)蛋白的表达。结果:EDA干预后能减轻阿霉素致心肌损伤小鼠的心肌形态学损伤,降低心肌酶活性。EDA可减少心肌组织中炎性因子TNF-α和IL-6蛋白的表达,改善小鼠抗氧化应激能力。EDA还能明显增加阿霉素小鼠心脏SIRT1蛋白表达,并抑制TGF-β1蛋白表达。结论:EDA对阿霉素心肌损伤具有保护作用,其作用机制可能通过调节SIRT1活性,抑制心脏TGF-β1蛋白表达,并提高机体抗氧化应激能力,从而减少阿霉素对心肌的损害。
[Abstract]:Objective: to investigate the protective effect of Edaravone (EDA) on adriamycin-induced myocardial injury in mice. Methods: adriamycin (3mg/kg) was injected intraperitoneally once every other day for 7 times to induce myocardial injury in mice. At the same time, the model was injected intraperitoneally with low and high dose of EDA (5 ~ 10 mg / kg) for 2 weeks. The changes of myocardium morphology, the activities of serum creatine kinase (CK) and lactate dehydrogenase (LDH), and the levels of inflammatory factor TNF- 伪 and interleukin 6 (IL-6), which reflect myocardial tissue, were observed under light microscope. Changes of (SOD), malondialdehyde (MDA) and nitric oxide (no) (NO) contents in myocardial tissue by colorimetric method; Western blot was used to detect the expression of transforming growth factor 尾 1 (TGF- 尾 1) and mammalian homologue 1 (SIRT1) of silencing signaling factor 2 in myocardial tissue. Results: after intervention of EDA, myocardial morphology and myocardial enzyme activity were reduced in mice with myocardial injury induced by doxorubicin. EDA decreased the expression of TNF- 伪 and IL-6 protein in myocardial tissue. EDA also significantly increased the expression of SIRT1 protein and inhibited the expression of TGF- 尾 1 protein in the heart of adriamycin mice. Conclusion: EDA has protective effect on myocardial injury induced by adriamycin, and its mechanism may be by regulating the activity of SIRT1, inhibiting the expression of TGF- 尾 1 protein in the heart, and increasing the ability of antioxidant stress, thus reducing the myocardial damage caused by doxorubicin.
【作者单位】：咸宁市第一人民医院心内科;
【分类号】：R965

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