吡格列酮对阿霉素所致小鼠心脏毒性保护作用  

Pioglitazone protects against doxorubicin-induced cardiotoxicity in mice

作　　者：李玲莉[1] 张宁[1] 魏文迎 胡灿[1] 唐其柱[1] Li Lingli;Zhang Ning;Wei Wenying;Hu Can;Tang Qizhu(Department of Cardiology,Renmin Hospital of Wuhan University,Wuhan University Cardiovascular Disease Institute,Hubei Provincial Key Laboratory of Cardiovascular Disease,Wuhan 430060,Hebei Province,China)

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,430060

出　　处：《中华老年心脑血管病杂志》2018年第8期862-866,共5页Chinese Journal of Geriatric Heart,Brain and Vessel Diseases

基　　金：国家自然科学基金(81470516)

摘　　要：目的研究吡格列酮对阿霉素所致的小鼠心脏毒性的保护作用。方法 8周龄健康雄性C57BL/6J小鼠28只,随机分为对照组、模型组、药物组(灌胃吡格列酮)和联合组(灌胃吡格列酮和腹腔注射GW9662),每组7只,后3组腹腔注射阿霉素5mg/kg,每周1次,持续4周,累积剂量达20mg/kg。4周后,存活小鼠进行相关检测,苏木精-伊红染色、Tunel染色、Western blot法及RT-PCR法检测小鼠心脏受损及凋亡情况。结果与对照组比较,模型组LVEF、短轴缩短率、心脏质量/胫骨长度、心肌细胞横截面积下降(P<0.05);心房钠尿肽(ANP)及B型钠尿肽(BNP)表达上调和细胞凋亡增加(P<0.05)。与模型组比较,药物组LVEF、短轴缩短率、心脏质量/胫骨长度、心肌细胞横截面积上升[(78.41±4.80)%vs(62.24±4.50)%,(46.63±5.09)%vs(33.35±3.35)%,(7.07±0.52)mg/mmvs(5.87±0.09)mg/mm,(191.93±9.52)μm2 vs(115.79±10.61)μm2,P<0.05)];ANP、BNP相对水平和细胞凋亡比下调[0.21±0.06 vs 1.22±0.18,0.28±0.04 vs 0.82±0.06,(6.40±2.09)%vs(61.34±3.28)%,P<0.05)];联合组抑制药物对小鼠心功能和凋亡的改善(P<0.05)。结论吡格列酮可能通过作用于过氧化物酶体增殖物激活受体γ介导其对阿霉素所致的小鼠心功能降低和心肌凋亡的保护作用。Objective To study the role of pioglitazone in protecting mice against doxorubicin-induced cardiotoxicity.Methods Twenty-eight healthy male C57 BL/6 J mice aged 8 weeks were randomly divided into control group,model group,drug group（pioglitazone gavage）and combination group（pioglitazone gavage＋intraperitoneal GW9662 injection）,7 in each group.The animals in model group,drug group and combination group received intraperitoneal doxorubicin injection（5 mg/kg once a week）for 4 weeks.The damage and apoptosis of myocardiocytes were detected by Western blot and PCR respectively with HE and Tunel staining.Results The LVEF,short axis shortening rate were lower while the ANP and BNP level and the apopotosis rate of myocardiocytes were significantly higher in model group than in control group（P〈0.05）.The LVEF,short axis shortening rate,heart weight/tibia length ratio were significantly higher,the cross-sectional area of myocardiocytes was significantly larger while the relative levels of ANP and BNP,and apopotosis rate of myocardiocytes were significantly lower in drug group than in model group（78.41%±4.80%vs 62.24%±4.50%,46.63%±5.09%vs 33.35%±3.35%,7.07±0.52 mg/mmvs 5.87±0.09 mg/mm,191.93±9.52μm2 vs 115.79±10.61μm2,0.21±0.06 vs 1.22±0.18,0.28±0.04 vs 0.82±0.06,6.40%±2.09% vs61.34%±3.28%,P〈0.05）.The cardiac function and apoptosis of myocardiocytes were not improved in combination group（P〈0.05）.Conclusion Pioglitazone can protect mice against doxorubicin-induced cardiac hypofunction and myocardial apoptosis by activating the PPARγ.

关 键 词：多柔比星 心脏毒素类 PPARΓ 抗肿瘤药 

分 类 号：R965[医药卫生—药理学]