摘要
目的:探讨吡格列酮对多柔比星(阿霉素)诱导心脏毒性的影响及其机制。方法:将小鼠随机分为正常对照组、模型组、吡格列酮组和吡格列酮+抑制剂(腹腔注射LY294002)组,后3组采用一次性腹腔注射多柔比星构建小鼠心脏毒性模型,持续4周后,观察小鼠心肌细胞形态和血液动力学指标变化,检测小鼠血清中乳酸脱氢酶(LDH)、肌酸激酶同工酶MB(CK-MB)、白细胞介素(IL)-6、IL-1β、肿瘤坏死因子-α(TNF-α)含量和心肌组织活性氧(ROS)活性、超氧化物歧化酶(SOD)活性、丙二醛(MDA)含量以及磷脂酰肌醇-3-激酶(PI3K)、蛋白激酶B(AKT)、磷酸化蛋白激酶B(p-AKT)蛋白表达水平。结果:与正常对照组比较,模型组心肌细胞出现空泡变性,LDH、CK-MB、MDA、IL-6、IL-1β、TNF-α含量和ROS活性升高,而左心室内压最大上升速率(+dp/dt)与左心室内压最大下降速率(-dp/dt)值和SOD活性以及PI3K、p-AKT蛋白表达水平降低(P<0.05);给予吡格列酮处理后,多柔比星建模引起的上述变化明显改善(P<0.05);给予PI3K/AKT通路抑制剂LY294002后,吡格列酮对心肌的保护作用明显逆转(P<0.05)。结论:吡格列酮可通过激活PI3K/AKT通路减轻心肌炎症和氧化应激损伤,改善多柔比星诱导的心脏毒性。
Objective: To investigate the protective effect and mechanism of pioglitazone on doxorubicin-induced cardiotoxicity.Methods: Mice were randomly divided into normal control group, model group,pioglitazone group and pioglitazone+inhibitor(intraperitoneal injection of LY294002) group, and the latter three groups were injected intraperitoneally with doxorubicin once to establish the model of cardiotoxicity. After four weeks, the changes of myocardial cell morphology and hemodynamics were observed. The levels of LDH, CK-MB, IL-6, IL-1β, and TNF-α in serum, as well as the ROS activity, SOD activity, and MDA content were assayed. The protein expression levels of PI3K, Akt, and p-Akt in myocardial tissue were detected.Results: Compared with those in the normal control group,the myocardial cells in the model group showed obvious vacuolar degeneration, the serum contents of LDH, CK-MB, MDA, IL-6, IL-1β, and TNF-α, as well as ROS activity were significantly higher,however, the values of the maximum rate of increase(+dp/dt) and the maximum rate of decrease(-dp/dt) of left ventricular pressure, the activity of SOD, and the protein expression levels of PI3K and p-AKT were significantly lower(P<0. 05);after pioglitazone treatment, the above changes caused by doxorubicin modeling were significantly improved(P<0. 05);and after administration of the PI3K/AKT pathway inhibitor LY294002, the protective effect of pioglitazone on myocardium was reversed significantly(P<0. 05).Conclusion: Pioglitazone can reduce myocarditis and oxidative stress injury by activating PI3K/AKT pathway, and ameliorate doxorubicin induced cardiotoxicity.
作者
车瑞芹
崔秀洁
马常满
CHE Ruiqin;CUI Xiujie;MA Changman(Dept.of Herbal Medicine,Chaoyang Central Hospital,Chaoyang 122000,Liaoning,China;Dept.of Oncology,Chaoyang Central Hospital,Chaoyang 122000,Liaoning,China;Dept.of Endocrinology,Chaoyang Central Hospital,Chaoyang 122000,Liaoning,China)
出处
《武汉大学学报（医学版）》
CAS
2021年第3期402-406,共5页
Medical Journal of Wuhan University
