结直肠癌常用化疗药引起肝损伤的研究

A study of the liver injury induced by the common used chemotherapy drugs in colorectal cancer

目的:以奥沙利铂、伊立替康等为主的化疗方案在结直肠癌肝转移中的应用逐渐增加,但目前一些临床观察表明,化疗可能影响肝脏损伤,进而影响新辅助化疗后围手术期的死亡率。本研究的目的是在健康小鼠腹腔中注射常用化疗药,明确应用不同化疗药引起肝损伤的类型及严重程度。方法:昆明小鼠反复腹腔注射生理盐水或伊立替康、奥沙利铂、5-FU/伊立替康及5-FU/奥沙利铂联合化疗。注射后处死小鼠,以组织学改变评估肝脏损伤类型。结果:在最大可耐受剂量下使用各种化疗药物,肝组织学未显示脂肪变性、纤维化或炎性浸润。与仅接受生理盐水腹腔注射的小鼠相比,接受5-FU/奥沙利铂联合化疗后小鼠肝组织VEGF mRNA表达水平无显著差异。结论:在无肿瘤负荷前提下,以5-FU、伊立替康、奥沙利铂为主的化疗,无肝损伤发生。此外,联合治疗也没有引起组织学改变。

Objective：Oxaliplatin or irinotecan in combination with 5-fluorouracyl（5-FU）and folinic acid are increasingly used in metastatic colorectal cancer to the liver before surgery. Some clinical observations have suggested that chemotherapy may induce liver damage,further more increase the per-operation fatal rate. The aim of this study was to evaluate the type and severity of the liver injury induced by the common used chemical therapy drugs with in-traperitoneal injection these drugs on health mice. Methods：KM mice accepted repeated intraperitoneal with different chemotherapy treatments,including saline,5-FU,irinotecan,oxaliplatin,a combination of 5 -FU/irinotecan or 5 -FU/oxaliplatin. After putted to death,morphological analyses were use to confirm the possible cause of the liver dam-age. Results：A variety of chemotherapeutic agents used at maximum tolerated doses compatible with survival,these regimens did not affect liver injury. Liver histology showed no steatosis,fibrosis or inflammation. The VEGF mRNA ex-pression between the mice treated with combined regimen of 5-FU/oxaliplatin and that accepted saline intraperitone-al injection showed no difference. Conclusion：Without tumor burden,the chemical therapy regimens including 5 -FU,irinotecan,oxaliplatin and combined treatments with 5-FU/irinotecan,5-FU/oxaliplatin induced no liver injury.