姜黄素抗环磷酰胺致染色体畸变的初步研究

摘要

目的 研究姜黄素对化疗药物环磷酰胺所致染色体畸变的影响.方法 昆明小鼠随机分成正常组,姜黄素组(100 mg/kg),模型组和环磷酰胺加姜黄素大、中、小剂量组(50、100、200 mg/kg).造模方法为腹腔注射环磷酰胺2次,浓度为50 mg/kg,2次间隔24 h.正常组(不造模)即阴性对照组,只喂基础饲料;模型组只注射环磷酰胺;姜黄素组(不造模)和环磷酰胺加姜黄素大、中、小剂量组在环磷酰胺给药前4周开始灌胃给药,每日1次.末次注射环磷酰胺24 h 后将全部小鼠脱颈椎处死,小鼠在处死前2～3 h腹腔注射秋水仙素,每10 g体重注射0.04%秋水仙素0.1 mL,以积累分裂相.处死后取小鼠股骨制备染色体标本.Giemsa染色观察小鼠染色体畸变情况,统计染色体总畸变率及不同类型的染色体畸变率.结果 姜黄素能显著降低环磷酰胺所致的染色体末端缺失及染色体碎片形成.姜黄素组与正常组比较没有明显差异,姜黄素本身不具有致畸性;低、中、高剂量姜黄素组染色体畸变率明显低于模型组(P＜0.05,P＜0.01),抑制率分别为19.65%、37.08%和17.22%,中剂量组影响最显著.不同类型染色体畸变方面,与模型组比较,不同剂量姜黄素组染色体末端缺失率明显下降(P＜0.05),多倍体形成没有显著差异;中剂量组对染色体碎片形成率有显著降低作用(P＜0.01).结论 姜黄素能减少由环磷酰胺所诱发的染色体畸变,姜黄素对环磷酰胺所致的染色体损伤有显著的保护作用.%Objective To study the influence of curcumin (Cur) on chromosomal aberration induced by cyclophosphamide (CTX, chemotherapeutics). Methods Kunming mice were randomly divided into the normal group, Cur group (100 mg/kg), model group, and group of CTX + low-dose Cur (low-dose group, 50 mg/kg), group of CTX + mid-dose Cur (mid-dose group, 100 mg/kg), group of CTX + high-dose Cur (high-dose group, 200 mg/kg). The normal group (negative control group) was fed basic forage. The model was established by intraperitoneal injection of CTX for 2 times in the dose of 50 mg/kg with 24 hours interval between 2 times. The model group was injected only CTX, and the Cur group,low-dose group, mid-dose group and high-dose group were given relevant medicinal intragastrically once a day 4 weeks before CTX injection. All mice were sacrificed 24 hours after the last CTX injection. The mice were injected intraperitoneally with 0.04％ colchicine (0.1 mL/10 g wt) 2 or 3 hours before sacrifice for accumulating mitotic figures. The femoral bones from the mice were collected to prepare chromosomal samples. The situation of chromosomal aberration, the total aberration rate and aberration rate of different chromosome types were observed by using Giemsa staining. Results Cur decreased significantly the deletion of chromosomal ends and formation of chromosomal fragments induced by CTX.The comparison between the Cur group and normal group showed no difference and Cur had no teratogenicity. The aberration rate was significantly lower in the low-dose group, mid-dose group and high-dose group than that in the model group (P ＜0.05, P ＜0.01), and was, respectively, 19.65％,37.08％ and 17.22％ showing the most significant influence in the mid-dose group. The deletion rate of chromosomal ends decreased significantly in the Cur groups of different doses (P ＜ 0.05), and there was no difference in the formation of polyploidy compared with the model group. The formation rate of chromosomal fragments was reduced significantly in the mid-dose group (P ＜ 0.01). Conclusion The results showed that Cur can reduce the chromosomal aberration induced by CTX, and has a significant preventive effect on chromosomal damage.