目的 探讨大鼠腹腔内植入氟尿嘧啶缓释剂(中人氟安)的不良反应及其机制.方法 选取56只健康雄性SD大鼠,随机分为生理盐水组、赋型剂对照组(L-聚乳酸)、中人氟安组(20mg)和普通氟尿嘧啶(5-FU)注射液组(20mg),每组14只.适应性饲养1周后开始实验.给药前、后检测各组大鼠体重、血常规及肝肾功能指标；给药第21天处死大鼠,观察腹腔脏器的粘连情况,HE染色光镜观察腹腔脏器、粘连组织的病理学改变.结果 与生理盐水组大鼠的体重增长比较,中人氟安组无明显差异,而5-FU注射液组大鼠的体重增长缓慢(P＜0.05).给药第7天,中人氟安组大鼠外周血白细胞、中性粒细胞、红细胞和血小板浓度分别为(11.46±0.71)×109/L、(1.75±0.14)×109/L、(6.47±0.28)×1012/L和(670.00±74.79)×109/L,与给药前水平相近；而普通5-FU注射液组大鼠外周血白细胞、中性粒细胞浓度分别为(8.73±0.54)×109/L和(0.52±0.12)×109/L,均低于给药前水平(P＜0.05).与给药前比较,给药第14天各组大鼠外周血的谷丙转氨酶、谷草转氨酶、血肌酐和尿素氮均无明显变化.中人氟安组大鼠的腹腔脏器粘连率为57.14％,明显高于普通5-FU注射液组的21.43％(P＜0.05)；其腹腔脏器间粘连程度亦较普通5-FU注射液组严重(P=0.045).HE染色光镜下观察中人氟安组大鼠的小肠、结肠和胃组织未见异常,而脾肝包膜、脾胃浆膜和胃肝包膜粘连紧密.结论 中人氟安大鼠腹腔内植入给药的毒性低,较为安全,但易引起大鼠腹腔脏器粘连,其粘连发生机制可能与药物颗粒植入方式及药物载体L-聚乳酸相关.%Objective To investigate the drug related adverse events, organ adhesion and its mechanism when sustained-release fluorouracil sinofuan was implanted to abdominal cavity of SD rats. Methods Fifty-six SD rats were divided into 4 groups randomly: control group (0.9% NS 10ml), excipient group ( L-polylactic acid), common 5-FU group (20mg) and sinofuan group ( 20mg). The general conditions and weight changes of rats were observed, and body weight curve was drawn. The indication of hema-tology, liver and kidney function were detected on d0, d7 and d14. Rats were executed on the 21st day, and the infra-abdominal intestinal tissue and adhesions in abdomen was observed by microscope after HE staining. Results Rats of sinofuan group and control group lived better, and the rats' weight of common 5-FU group increased slowly compared with that of sinofuan group and control group. After administration on the 7 th day, the levels of leukocyte, neutrophill, erythrocyte and platelet in sinofuan group were (11.46±0. 71) x 109/, (0. 75 ±0. 14) × 109/L, (6. 47 ±0.28) × 10l2/L and (670.00 ±74.79) × 109/L, which were similar to the levels before administration ( P > 0. 05 ). Compared with the levels of leukocyte and neutrophil before administration, those in common 5-FU group were decreased obviously [ (11.49 ±0. 94) × 109/L vs. (8.73±0.54) × 109/L and (1.69±0.21) × 109/L vs. (0.52±0.12) x 109/L], showing significant differences (P <0.05). The indication of liver and kidney functions of all groups showed no difference (P > 0. 05). On the 21st day, there were adhesions in hepatic gap, hepatogastric gap, liver and spleen gap and abdominal organs of rats in each group except control group. The adhesion rate of sinofuan group was higher than that of common 5-FU group (57. 14% vs. 21.43%), showing significant differences (P < 0. 05). Conclusion Sinofuan implanted to abdominal cavity of SD rats leads to mild hematologic toxicity, no liver and kindy dysfunction and higher adhesion rate compared with common 5-FU. The mechanism of higher adhesion of sinofuan in SD rats may be associated with implanting and L-polylactic acid.
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