Objective To explore the in vivo exposure levels of cigarette smoking ( CS) by measuring the biomar-kers nicotine and cotinine. Methods One hundred and sixty male SD rats were divided into 15 cigarette exposure groups (10, 20 and 30 nonfilter cigarettes/day, for 2, 4, 6, 8 and 12 weeks) and a control group (without CS exposure). The rats were sacrificed at different time?points. The concentration of plasma nicotine and cotinine were measured by GC?MS/MS. Results The CS?exposed rats displayed decreased locomotor activity, ataxic gait, irregular respiration, nasal noise, and salivation after smoking exposure for 3 weeks. Rats in the CS exposure groups had lower body weight, and the reduction of body weight was time and dose related (P<0. 01). The retention time of nicotine was 7. 5 to 8. 5 min. The concentra?tion of plasma nicotine in the CS exposure groups was higher than control group (155 ± 56. 65) ng/mL. The retention time of cotinine was 11. 5 to 12. 5 min, the concentrations of plasma cotinine in CS exposure groups were higher than control group (340 ± 41. 97) ng/mL, the increase of plasma cotinine in CS groups was time?related (P<0. 05), and the exposure concentration and duration had synergistic effect on the level of plasma cotinine ( P<0. 05 ) . Conclusions CS exposurecauses structural damages in male rats. The plasma concentration of cotinine can effectively reflect the in vivo exposure lev?els of cigarette smoking, and well presents a dose?response relationship.%目的 通过对吸烟大鼠血浆尼古丁、可替宁含量的测定,探讨香烟在体内的内暴露水平.方法 清洁级SD雄性大鼠160只,随机分为2、4、6、8、12周的低、中、高染毒剂量组及对照组,每组10只.采用呼吸道静式染毒,每日染毒一次,染毒周期为2、4、6、8、12周.观察大鼠的一般毒性效应,运用气相色谱-质谱联用法检测吸烟大鼠血浆中尼古丁、可替宁的含量.结果 香烟烟雾暴露组大鼠在第3周后逐渐开始出现间歇咳嗽,腹式呼吸加剧,鼻噪音等症状,暴露时间越长,症状越明显;染毒剂量越高,染毒周期越长,大鼠体重减少越明显,与空白对照组相比,差异有显著性(P<0.01);大鼠血浆尼古丁的保留时间为7.5~8.5 min,随暴露时间的延长,暴露剂量的增加,大鼠血浆中尼古丁含量较空白对照组(155±56.65)ng/mL有所增加;大鼠血浆可替宁的保留时间为11.5~12.5 min;随暴露时间的延长,暴露剂量的增加,大鼠血浆中可替宁含量较空白对照组(340±41.97)ng/mL有所增加,且呈现剂量?反应关系,不同暴露周期间可替宁含量的差异有显著性(P<0.05),且暴露时间与暴露剂量存在交互效应(P<0.05).结论 香烟烟雾暴露可造成大鼠机体不同程度的损伤,大鼠血浆可替宁浓度能够有效反映香烟烟雾内暴露情况,且呈现较好的剂量?反应关系.
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