摘要 目的 探讨顺铂联合胸部单次大剂量照射对小鼠心脏的放射生物学效应。 方法 雄性SPF级昆明种小鼠80只,随机均分为4组,A组小鼠第1、5、9、13天腹腔灌注顺铂(6 mg/kg);B组小鼠仅第1天以6MV-X线20 Gy单次照射小鼠胸部;C组小鼠第1、5、9、13天腹腔灌注顺铂(6 mg/kg),同时仅第1天以6MV-X线20 Gy单次照射胸部。D组小鼠为对照组,腹腔灌注等剂量的生理盐水及给予自然光照。观察各组小鼠一般状况,第2、4、8、12、16周检测小鼠血清心肌酶的变化,并采用苏木精-伊红(HE)染色观察小鼠心脏的形态学改变,应用免疫组织化学法检测小鼠心脏组织中B淋巴细胞瘤-2蛋白(BCL-2蛋白)及BCL-2相关X蛋白(BAX蛋白)的表达率。 结果 A、B、C组小鼠体质量均呈下降趋势,且小鼠心肌组织出现不同程度的病理改变,早期以炎性反应、后期以纤维化为主。在相同时间血清中肌钙蛋白I(cTnI)及谷草转氨酶(AST)水平、心肌组织中BCL-2蛋白和BAX蛋白表达率多组间比较差异均有统计学意义(FcTnI=40.67~105.86,FAST=19.87~34.84,FBCL-2=27.31~93.82,FBAX=68.76~122.45,P<0.01);在相同时间各指标两两间比较,除A组和B组间差异无统计学意义外(P>0.05),其余各组间比较差异均有统计学意义(P<0.01)。 结论 顺铂同步单次大剂量照射所引起的心脏损伤较单纯化疗或放疗严重,给予小鼠腹腔灌注顺铂总剂量达到24 mg/kg时与单次大剂量照射引起心脏损伤的程度相似,发生机制可能与心肌组织中BAX蛋白表达增加、BCL-2蛋白表达减少有关。 Abstract:Objective To investigate the radiobiological effect of cisplatin combined with single high-dose chest radiation on the heart of mice. Methods A total of 80 male specific pathogen-free Kunming mice were randomized into groups A, B, C, and D. The mice in group A were given peritoneal perfusion of cisplatin (6 mg/kg) on days 1,5,9, and 13, those in group B were given one-time chest irradiation alone with 6MV X-ray at a single dose of 20 Gy on day 1, and those in group C were given peritoneal perfusion of cisplatin (6 mg/kg) on days 1,5,9, and 13 combined with one-time chest irradiation with 6MV X-ray at a single dose of 20 Gy on day 1. Group D was the control group and the mice in this group were given natural light and peritoneal perfusion of an equal volume of normal saline. The general status of mice was observed. At weeks 2,4,8,12, and 16, the changes in serum myocardial enzymes were measured; HE staining was used to observe morphological changes of the heart; immunohistochemistry was used to measure the protein expression of B-cell lymphoma-2 (BCL-2) and BCL-2-associated X protein (BAX protein) in heart tissue. Results Groups A, B, and C had a trend of reduction in body weight and varying degrees of pathological changes of the myocardial tissue, with inflammatory response in the early stage and fibrosis in the late stage. There were significant differences between the four groups in serum levels of cardiac troponin I (cTnI) and aspartate aminotransferase (AST) and protein expression rates of BCL-2 and BAX in the myocardial tissue at each time point (FcTnI=40.67-105.86,FASt=19.87-34.84,FBCL-2=27.31-93.82,FBAX=68.76-122.45,P<0.01). There were significant differences in these indices at each time point between any two groups (P<0.01), except between groups A and B (P>0.05). Conclusion Cardiac injury caused by cisplatin combined with