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目的:探讨血小板生成素(TPO)对大鼠多柔比星(ADM)心血管损伤的拮抗作用及其机制。方法:32只Wistar大鼠被随机分成对照组、ADM组、ADM+TPOL组和ADM+TPOH组。对照组给予生理盐水,其余各组给予ADM20mg/kg腹腔内注射,2个TPO干预组则加用10或30μg/kg的TPO(隔天1次,共3次)。ELISA法测大鼠血清CK-MB及cTNI;电镜下观察心肌细胞超微结构;免疫组化染色观察心肌细胞及血管内皮细胞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-OHdGindex。结果:TPO干预组大鼠一般状况改善,浆膜腔积液减少;TPO干预组CK-MB(14.65±1.91、14.21±1.70)和cTNI(9.66±1.31、10.07±1.20)的活力较ADM组(19.58±3.49、12.50±1.62)明显下降,P值分别为0.000、0.001及0.001、0.005;ADM组心肌细胞超微结构损害较TPO干预组严重;TPO干预组心血管病理改变减轻,IOD(11.59±3.86、12.63±3.36)和8-OHdGindex(1.13±0.91、1.50±0.98)值分别较对应ADM组(23.39±7.83、4.98±2.65)明显降低,P值分别为0.009、0.009及0.022、0.023;上述指标在TPO干预组间差异无统计学意义,P>0.05。结论:TPO通过拮抗多柔比星心血管的氧化损伤来发挥心脏保护作用。
Objective: To investigate the antagonistic effect of thrombopoietin (TPO) on cardiovascular injury induced by doxorubicin (ADM) in rats and its mechanism. Methods: Thirty-two Wistar rats were randomly divided into control group, ADM group, ADM + TPOL group and ADM + TPOH group. The control group received normal saline. The other groups received intraperitoneal injections of ADM 20 mg / kg. Two TPO intervention groups received TPO (10 or 30 μg / kg once daily for 3 times). The serum CK-MB and cTNI were measured by ELISA. The ultrastructure of myocardial cells was observed under electron microscope. The expression of 8-OHdG in myocardial cells and vascular endothelial cells was detected by immunohistochemistry. The cumulative optical density (IOD) and 8-OHdGindex were calculated. Results: The general condition of TPO intervention group was improved and the effusion of serous fluid was decreased. The activity of CK-MB (14.65 ± 1.91, 14.21 ± 1.70) and cTNI (9.66 ± 1.31, 10.07 ± 1.20) 19.58 ± 3.49,12.50 ± 1.62), P values were 0.000,0.001 and 0.001,0.005, respectively. The ultrastructural damage of cardiomyocytes in ADM group was more serious than that in TPO group. The cardiovascular pathological changes in ITP group were lower than those in ITP group (11.59 ± 3.86,12.63 ± 3.36) and 8-OHdGindex (1.13 ± 0.91,1.50 ± 0.98) were significantly lower than the corresponding ADM group (23.39 ± 7.83,4.98 ± 2.65), P values were 0.009,0.009 and 0.022,0.023 respectively; There was no significant difference between the two groups in TPO intervention (P> 0.05). CONCLUSION: TPO exerts cardioprotective effect by antagonizing the cardiovascular injury of doxorubicin.