車菲菲 1,2 , 徐娟 1 , 劉瑜 1 , 徐才剛 1
  • 1 四川大學(xué)華西醫(yī)院血液科（成都，610041）;2 四川省醫(yī)學(xué)科學(xué)院?四川省人民醫(yī)院血液科;

【摘要】　目的　 采用多柔比星（doxorubicin，DOX）制備心肌損傷動(dòng)物模型，評(píng)價(jià)各種檢測(cè)心功能變化方法的意義。 　方法　 14只新西蘭大白兔，DOX耳緣靜脈注射，每周3 mg/kg，共10周。分別于給藥前、第4周末及實(shí)驗(yàn)結(jié)束時(shí)測(cè)定血清肌鈣蛋白Ⅰ（cTnI）和腦鈉肽（BNP）水平，彩色多普勒超聲心動(dòng)圖檢測(cè)心功能變化，并觀察心肌組織病理形態(tài)學(xué)改變及心肌細(xì)胞凋亡情況。　結(jié)果　 使用DOX前后對(duì)比，血清cTnI和BNP濃度升高（P lt;0.05）；左室射血分?jǐn)?shù)（LVEF）和左室短軸縮短率（LVFS）下降（P lt;0.05）；心肌組織病理顯示心肌細(xì)胞出現(xiàn)不同程度的空泡變性與水腫，細(xì)胞間隙明顯增寬，大量炎性細(xì)胞浸潤(rùn)。心肌細(xì)胞凋亡明顯增加。　結(jié)論　 結(jié)合心臟超聲檢查和血清cTnI、BNP指標(biāo)檢測(cè)可判斷心肌損傷程度。
【Abstract】　Objective　 To observe the changes of heart function caused by doxorubicin in rabbits.　Methods　 A total of 14 New-Zealand white rabbits were intravenous-injected with doxorubicin with a dosage of 3 mg/kg intravenously once a week, and the accumulative dose was 30 mg/kg. Before the medication and at the 4th and 10th weekend after the medication, the serum levels of cardiac troponin I (cTnI) and brain natriuretic peptide (BNP) were measured; left ventricular ejection function (LVEF) and left ventricular fractional shortening (LVFS) were performed on the rabbits respectively. At the 10th weekend, the pathological changes of cardiac tissue and the apoptosis of myocardial cell were detected.　Results　 The levels of cTnI and BNP significantly increased (P lt;0.05), and the LVEF and LVFS markedly decreased (P lt;0.05) after the administration of doxorubicin. Uneven vacuolar degeneration and edema of cardiocytes could be observed with a wide cell spaces and inflammatory cell infiltration in the histopathological slices.　Conclusion　 The combined application of heart sonography with the detection of the serum levels of cTnI and BNP can evaluate the degree of myocardial damage of the rabbits models very well.

引用本文： 車菲菲,徐娟,劉瑜,徐才剛. 多柔比星致兔心功能變化的實(shí)驗(yàn)研究. 華西醫(yī)學(xué), 2010, 25(12): 2167-2170. doi: 復(fù)制

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12. 　Yeh ET, Tong AT, Lenihan DJ, et al. Cardiovascular complications of cancer therapy: diagnosis, pathogenesis, and management[J]. Circulation, 2004, 109(25): 3122-3131.
  1. 1. 　Lefrak EA, Pitha J, Rosenheim S, et al. A clinicopathologic analysis of adriamycin cardiotoxicity[J]. Cancer, 1973, 32 (2): 302-314.
  2. 2. 　Ivona Klimtová. Comparative study of chronic toxic effects of daunorubicin and doxorubicin in rabbits[J]. Hum Exp toxicol, 2002, 21(12): 649-657.
  3. 3. 　Dragojevic-Simic VM, Dobric SL, Bokonjic DR, et al. Amifostine protection against doxorubicin cardiotoxicity in rats[J]. Anticancer Drugs, 2004, 15(2): 169-178.
  4. 4. 　Aupperle H, Garbade J, Schubert A, et al. Effects of autologous stem cells on immunohistochemical patterns and gene expression of metalloproteinases and their tissue inhibitors in doxorubicin cardiomyopathy in a rabbit model[J]. Vet Pathol, 2007, 44(4): 494-503.
  5. 5. 　Kawada T, Yamazaki T, Akiyama T, et al. Chronic adriamycin treatment impairs myocardial interstitial neuronal release of norepinephrine and epinephrine[J]. J Cardiovasc Pharmacol, 2000, 36(Suppl 2): 31-34.
  6. 6. 　Barcin C, Kursaklioglu H, Safali M, et al. Effect of octreotide in the prevention of doxorubicin cardiotoxicity[J]. Anadolu Kardiyol Derg, 2005, 5(1): 18-23.
  7. 7. 　Aiken MJ, Suhag V, Garcia CA, et al. Doxorubicin-induced cardiac toxicity and cardiac rest gated blood pool imaging[J]. Clin Nucl Med, 2009, 34(11): 762-767.
  8. 8. 　Kim SY, Kim SJ, Kim BJ, et al. Doxorubicin-induced reactive oxygen species generation and intracellular Ca2+ increase are reciprocally modulated in rat cardiomyocytes[J]. Exp Mol Med, 2006, 38(5): 535-545.
  9. 9. 　Lipshultz SE, Lipsitz SR, Sallan SE, et al. Chronic progressive cardiac dysfunction years after doxorubicin therapy for childhood acute lymphoblastic leukemia[J]. J Clin Oncol, 2005, 23(12): 2629-2636.
  10. 10. 　Adamcova M, Simunek T, Kaiserova H, et al. In vitro and in vivo examination of cardiac troponins as biochemical markers of drug-induced cardiotoxicity[J]. Toxicology, 2007, 237(1-3): 218-228.
  11. 11. 　Maisel AS, Krishnaswamy P, Nowak RM, et al. Rapid measurement of B-type natriuretic peptide in the emergency diagnosis of heart failure[J]. N Engl J Med, 2002, 347(3): 161-167.
  12. 12. 　Yeh ET, Tong AT, Lenihan DJ, et al. Cardiovascular complications of cancer therapy: diagnosis, pathogenesis, and management[J]. Circulation, 2004, 109(25): 3122-3131.