CAJ | 학술논문

目的探讨苯染毒对C57BL/6小鼠骨髓单个核细胞多药耐药基因1(multidrug resistance 1,MDR1)基因和P-糖蛋白(P-glycoprotein,P-gp)表达的影响.方法实验动物随机分为对照组、低剂量组、中剂量组、高剂量组,每组24只,分别以单纯玉米油及25、50、100 mg/kg剂量苯灌胃染毒C57BL/6小鼠,每日1次,每周5次,连续染毒4周,染毒12、26、29 d后分批处死小鼠,检测C57BL/6小鼠外周血常规,实时定量PCR检测骨髓单个核细胞MDR1基因表达,免疫印迹法检测骨髓单个核细胞的P-gp表达.结果染毒12d,高剂量组红细胞、血红蛋白明显低于对照组、低剂量组、中剂量组,差异有统计学意义(P＜0.01、P＜0.05).染毒26 d,高剂量组白细胞明显低于对照组、低剂量组、中剂量组,差异有统计学意义(P＜0.01、P＜0.05).各时间点各染毒组的MDR1基因mRNA表达均明显低于对照组,差异均有统计学意义(P＜0.01).染毒26 d,高剂量组P-gp表达低于对照组、低剂量组和中剂量组,中剂量组P-gp表达低于低剂量组,差异均有统计学意义(P＜0.01、P＜0.05)；染毒29 d,各染毒组P-gp表达均低于对照组,差异均有统计学意义(P＜0.05).结论苯染毒干扰骨髓单个核细胞MDR1基因和P-gp表达,可能是苯血液毒性的机制之一.
목적 탐토분염독대C57BL/6소서골수단개핵세포다약내약기인1(multidrug resistance 1,MDR1)기인화P-당단백(P-glycoprotein,P-gp)표체적영향.방법 실험동물수궤분위대조조、저제량조、중제량조、고제량조,매조24지,분별이단순옥미유급25、50、100 mg/kg제량분관위염독C57BL/6소서,매일1차,매주5차,련속염독4주,염독12、26、29 d후분비처사소서,검측C57BL/6소서외주혈상규,실시정량PCR검측골수단개핵세포MDR1기인표체,면역인적법검측골수단개핵세포적P-gp표체.결과 염독12d,고제량조홍세포、혈홍단백명현저우대조조、저제량조、중제량조,차이유통계학의의(P＜0.01、P＜0.05).염독26 d,고제량조백세포명현저우대조조、저제량조、중제량조,차이유통계학의의(P＜0.01、P＜0.05).각시간점각염독조적MDR1기인mRNA표체균명현저우대조조,차이균유통계학의의(P＜0.01).염독26 d,고제량조P-gp표체저우대조조、저제량조화중제량조,중제량조P-gp표체저우저제량조,차이균유통계학의의(P＜0.01、P＜0.05)；염독29 d,각염독조P-gp표체균저우대조조,차이균유통계학의의(P＜0.05).결론 분염독간우골수단개핵세포MDR1기인화P-gp표체,가능시분혈액독성적궤제지일.
Objective To investigate the effects of benzene poisoning on the expression of multidrug resistance 1 (MDR1) gene and P-glycoprotein (P-gp) in the bone marrow mononuclear cells (BMMNCs) of C57BL/6 mice.Methods C57BL/6 mice were randomly divided into control group (n=24),low-dose group (n=24),medium-dose group (n=24),and high-dose group (n=24) to receive corn oil,25 mg/kg benzene,50 mg/kg benzene,or 100 mg/kg benzene by gavage,once daily,5 days/weeks,for 4 weeks.The mice were sacrificed on day 12,26,or 29 of poisoning.Peripheral blood routine test was performed; real-time quantitative PCR was used to measure the MDR1 gene expression in BMMNCs; Western blot was used to measure the P-gp expression in BMMNCs.Results On day 12,the red blood cell count and hemoglobin level in the high-dose group were significantly lower than those in the control group,low-dose group,and medium-dose group (P＜0.01 or P＜0.05).On day 26,the white blood cell count in the high-dose group was significantly lower than those in the control group,low-dose group,and medium-dose group (P＜0.01 or P＜0.05).At each time point,the mRNA expression of MDR1 gene in the low-dose group,medium-dose group,and high-dose group was significantly lower than that in the control group (P＜0.01).On day 26,the P-gp expression in the high-dose group was significantly lower than those in the control group,low-dose group,and medium-dose group,and the P-gp expression in the medium-dose group was significantly lower than that in the low-dose group (P＜0.01 or P＜ 0.05).On day 29,the P-gp expression in the low-dose group,medium-dose group,and high-dose group was significantly lower than that in the control group (P＜0.05).Conclusion Benzene poisoning can affect the expression of MDR1 gene and P-gp,which may be one of the mechanisms of benzene hematotoxicity.