NADPH氧化酶在阿霉素心脏毒性的表达及意义  

The significance of NADPH oxidases expression in adriamycin induced cardiotoxicity

作　　者：王震[1] 王梦龙[1] 刘剑芳[1] 叶晶[1] 徐瑶[1] 姜慧敏[1] 叶迪 万军[1] 

机构地区：[1]武汉大学人民医院心血管内科,武汉大学心血管病研究所,心血管病湖北省重点实验室,武汉430060

出　　处：《中国循证心血管医学杂志》2018年第2期164-166,169,共4页Chinese Journal of Evidence-Based Cardiovascular Medicine

基　　金：国家自然科学基金(81170208)

摘　　要：目的探讨NADPH氧化酶(Nox)在阿霉素心脏毒性中的表达及意义。方法选择40只SPF级雄性C57BL/6J小鼠,随机分成为对照组和模型组,每组各20只,模型组小鼠通过一次性腹腔注射20mg/kg阿霉素诱导心脏毒性,对照组小鼠给予等量生理盐水。2组小鼠均观察5 d后处死,测量并记录体重、心重和胫骨长度,计算心重胫骨长度比,同时行心肌组织荧光TUNEL染色观察心肌细胞凋亡情况。应用Real time-PCR和Western blots法检测小鼠心肌组织Nox2和Nox4 mRNA和蛋白表达。结果与对照组相比,模型组小鼠体重、心重和心重胫骨长度比明显下降(P均<0.05);TUNEL染色结果显示模型组小鼠心肌组织凋亡指数明显升高(P<0.05);模型组小鼠心肌组织中Nox2和Nox4 mRNA和蛋白质表达均较对照组明显上调(P均<0.05)。结论在阿霉素心脏毒性模型,小鼠心肌组织中Nox2和Nox4表达增高,提示Nox通过调控氧化应激参与阿霉素心脏毒性作用,且可能是阿霉素心脏毒性的潜在治疗靶点。Objective To explore the significance of NADPH oxidases expression in Adriamycin （ADR） induced cardiotoxicity. Methods 40 male C57BL/6J mice were randomly divided into control group and model group, each group had 20 mice. The model group was given intraperitoneal ADR （20 mg/kg） in one time, while the control group was given equivalent saline （20 mg/kg） in the same way. On the 5th day, all the mice were killed to measure and record their body weight, heart weight and ratio of tibia length to heart weight. Meanwhile, the myocardial apoptosis was examined using terminal deoxynucleotidyl transferase dUTP nick end labeling （TUNEL） assay. The expression of mRNA and protein in Nox2 and Nox4 were measured by RT-PCR assay and western blotting in mouse myocardium. Results Compared with control group, the body weight, heart weight and ratio of tibia length to heart weight of mice in the model group with ADR treatment got significant reduction （P〈0.05）; TUNEL staining results showed that the apoptosis rate of myocardial tissue increased significantly in model group （P〈0.05）. RT-PCR and Western blotting show that the expression of Nox2 and Nox4 in ADR group mice were significantly higher than those in control group （P〈0.05）. Conclusion In the model of ADR-induced cardiotoxicity, the expression of Nox2 and Nox4 is significantly higher than that in control group, which indicated that Nox might be a potential therapeutic target for cardiotoxicity induced by ADR.

关 键 词：NADPH氧化酶 氧化应激 阿霉素 凋亡 

分 类 号：R541.8[医药卫生—心血管疾病]