血小板生成素对大鼠多柔比星亚急性/慢性心脏损伤的影响

目的通过建立大鼠多柔比星（DOX）亚急性/慢性心肌损伤模型来观察血小板生成素（TPO）对多柔比星心肌毒性的影响并探索其机制。方法 30只Wistar大鼠被随机分成3组,分别为对照组、DOX组、DOX＋TPO组。对照组给予0.9%氯化钠溶液10mL/kg,其余各组给予DOX1mg/kg腹腔内注射,每周5次,共3周;TPO干预组则给予TPO5μg/kg,每天1次,共21d。实验第8周处死大鼠,测定大鼠肌酸激酶同工酶（CK-MB）、心肌钙蛋白I（cTNI）、丙二醛（MDA）、超氧化物歧化酶（SOD）、谷胱甘肽过氧化物酶（GSH-Px）活性;应用超声心动图记录大鼠心脏功能参数（HR、LVDEE、LVESD、CO）;通过HE染色,观察心肌组织学改变;利用电子显微镜了解心肌细胞超微结构的变化;采用免疫组化的方法观察心肌细胞DNA氧化损伤产物8-羟基脱氧鸟苷（8-OHdG）表达情况,计算累积光密度（IOD）及8-OHdG index。结果 （1）TPO干预组CK-MB、cTNI其活力较DOX组明显下降（P〈0.01）;（2）与DOX组比较,DOX＋TPO组SOD及GSH-Px较高（P〈0.01）,而MDA较低（P〈0.01）;（3）TPO干预组心功能参数LVDEE、LVESD较DOX组对应值减低（P〈0.05）,而CO则明显增加（P〈0.01）;（4）电子显微镜下DOX组心肌细胞超微结构损害明显,给予TPO后变化减轻;（5）TPO干预组心肌细胞IOD和8-OHdG index较DOX组明显下降（P〈0.01）。结论 TPO通过抗氧化损伤来拮抗大鼠多柔比星所致的亚急性/慢性心脏损害。

Effect of thrombopoietin providing against doxorubicin -induced subacute or chronic heart injury in rats

Objective To observe the effect of thrombopoietin on doxorubicin-induced subacute or chronic heart toxicity in rats model and explore the mechanism.Methods Thirty Wistar rats were randomized into three groups(n = 10):Control group,DOX group,DOX+TPO group.The control group was given saline 10 mL/Kg,while the other two groups were given doxorubicin at the dosage of 1 mg/kg imtraperitoneal injection,five times per week for 3 weeks.DOX+TPO groups were injected TPO at the dosages of 5 μg/kg,once a day,a total of 21 days.All the rats were killed at 8 weeks.The activity of CK-MB,cTNI,malondialdehyde(MDA)、superoxide dismutase(SOD) and Glutathione peroxidase(GSH-Px) in rats were measured.The cardiac function parameters of LVEDD、LVESD、HR、CO were detected by echocardiography.By HE staining,pathological change was found.The ultrastructure change of cardiocyte was observed by the electron microscope.By immunohistochemistry staining,the expression level of 8-hydroxy-2’-deoxyguanosin(8-OHdG) produced by DNA oxidative damage in cardiocyte were detected.IPP 6.0 software was used to detect IOD and calculate the 8-OHdG index.Results(1)The energy of CK-MB and cTNI of TPO groups were obviously lower than corresponding value of DOX group(P < 0.01);(2) Compared with DOX group,the activity of SOD and GSH-Px was higher(P < 0.01),but that of MDA was lower(P < 0.01);(3)The cardiac function parameters of LVDEE and LVESD of TPO group were significantly lower than corresponding value of DOX group and that of CO was higher than DOX group(P < 0.01);(4)The ultrastructure of cardiocyte in the DOX group was damaged more severely than TPO group;(5)IOD and 8-OHdG index of TPO groups were lower than corresponding value of DOX group(P < 0.01).Conclusion TPO can provide the protection by rivalrying doxorubicin-induced oxidative damage of subacute or chronic heart in rat.