摘要
目的探讨氯乙烯(vinyl chloride monomer,VCM)亚慢性染毒对大鼠肝细胞周期以及microRNA21(mir-21)和microRNA192(mir-192)表达量的影响。方法将32只健康斯普拉-道来(sprague dawley,SD)大鼠随机分为三个实验组(5 mg/kg组,25 mg/kg组和125 mg/kg组)与一个对照组(25 mg/kg清洁空气组),每组8只。采用腹腔注射进行VCM染毒,每周3次(隔日染毒)。染毒12周,处死大鼠并摘取肝组织。制备肝单细胞悬液,使用流式细胞技术检测G0/G1期、S期和G2/M期肝细胞所占百分比;提取肝细胞中的小片段RNA(<200 nt),采用实时荧光定量PCR技术检测大鼠肝细胞中mir-21和mir-192的表达量。结果 VCM染毒大鼠G0/G1期、S期和G2/M期肝细胞所占百分比在各剂量组间差异均无统计学意义(均有P>0.05);125 mg/kg组S期细胞与对照组相比明显增加,差异有统计学意义(t=-4.363,P=0.024)。各剂量组之间mir-21相对表达量差异有统计学意义(H=16.064,P=0.001);与对照组和5 mg/kg组相比,25 mg/kg组及125 mg/kg组mir-21相对表达量均降低,差异均有统计学意义(均有P<0.05)。各剂量组之间mir-192相对表达量差异有统计学意义(H=15.939,P=0.001);与对照组和5 mg/kg组相比,25 mg/kg组及125 mg/kg组mir-192相对表达量均降低,差异均有统计学意义(均有P<0.05)。结论 VCM亚慢性染毒导致大鼠肝细胞S期比例增加,mir-21和mir-192表达下调,具体调节机制有待进一步研究。
Objective To explore the sub-chronic toxicity effects of vinyl chloride monomer (VCM) on cell cycle and the expression of cell cycle related microRNA 21 (mir-21) and microRNA 192 (mir-192) of rat liver. Methods Thirty-two healthy sprague dawley (SD) rats were randomly divided into three VCM exposure groups (5 mg/kg, 25 mg/kg and 125 mg/kg) and a control group (25 mg/kg clean air). The rats were exposed by intraperitoneal injection three times a week (every other day) for three months. The flow cytometry was used to measure the percent of each phase( GO/G1, S, and G2/M). The mir-21 and mir-192 was extracted and then quantified using real-time fluorescent quantitative PCR. Resuits The percentage of each phase of cell cycle was not significantly different among four groups ( all P 〉 0. 05). The proportion of S-phase cells in 125 mg/kg group was higher than the control group(t = -4. 363 ,P =0. 024). Besides, the expressions of mir-21 varied significantly among four groups (H = 16. 064, P =0. 001 ) and, furthermore, decreased signif- icantly in both 25 mg/kg and 125 mg/kg group when they were compared with control and 5 mg/kg group ( all P 〈 0. 05 ). Meanwhile, the expressions of mir-192 also varied significantly (H = 15. 939; P = 0. 001 ), and decreased significantly in both 25 mg/kg and 125 mg/kg group, compared with control and 5 mg/kg group (all P 〈 0. 05 ). Conclusions VCM subchronic exposure induced the increase of S-phase cells and decrease of the expression of mir-21 and mir-192.
出处
《中华疾病控制杂志》
CAS
CSCD
北大核心
2016年第10期1057-1060,共4页
Chinese Journal of Disease Control & Prevention
基金
山西省基础研究计划项目(2013011059-1)