气管滴注大气细颗粒物及硫酸镍对大鼠凝血功能影响的比较
Comparative Study on Parameters of Blood Coagulation Affected by PM2.5 and Nickel Sulfate Intratracheal Instillation in Rats
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摘要:
目的 观察大气细颗粒物(PM2.5)及硫酸镍(NiSO4)对大鼠凝血功能的急性影响,以期在一定程度上解释PM2.5的可能作用成分和作用机制。 方法 本研究分为PM2.5和NiSO4染毒实验两部分。每部分实验均将28只雄性Wistar大鼠随机分为4组。PM2.5染毒实验:对照组及7.5、15、30mg/kg体重3个染毒剂量组(低、中、高剂量组);NiSO4染毒实验:对照组及7.5、75、750μg/kg体重3个染毒剂量组(低、中、高剂量组)。其中,PM2.5中剂量组(15mg/kg体重)对应的镍含量与NiSO4低剂量组(7.5μg/kg体重)相同。PM2.5和NiSO4均采用一次性气管滴注染毒,染毒24h后处死动物,腹主动脉取血,测定不同染毒组大鼠血中凝血相关指标水平,包括凝血酶原时间(PT)、活化部分凝血活酶时间(APTT)、纤维蛋白原(Fib)及组织因子(TF)。 结果 与对照组相比,PM2.5各染毒组血浆PT水平明显降低(P<0.05);中、高剂量组的PM2.5可引起大鼠血浆Fib水平明显升高(P<0.05)。不同剂量组的PM2.5均可引起大鼠TF的升高,其中以低剂量组的作用最明显。研究未见PM2.5对大鼠血中APTT的影响。高剂量组的NiSO4引起大鼠血浆Fib水平升高(P<0.05)。中、高剂量NiSO4染毒组大鼠血中TF均明显升高(P<0.05)。未见NiSO4染毒组大鼠血浆PT和APTT的变化。含相同剂量镍的PM2.5与NiSO4相比,PM2.5的效应更强。 结论 PM2.5气管滴注可导致大鼠凝血功能改变,主要表现为外源性凝血途径指标异常。NiSO4染毒出现相似毒性效应,高剂量NiSO4能使大鼠血浆Fib和TF水平升高。提示镍可能在PM2.5致大鼠凝血功能改变中发挥作用。 Abstract:Objective To investigate the acute toxic effects of PM2.5 and nickel sulfate (NiSO4), a toxic metal components in PM2.5, on blood coagulation in Wistar rats. Methods Twenty-eight male Wistar rats were divided into four groups for each experiment. In PM2.5 experiment, PM2.5 was administered by intratracheal instillation at the single dose of 0 mg/kg, 7.5 mg/kg, 15 mg/kg and 30mg/kg, respectively. In NiSO4 experiment, NiSO4 was administered under the same manner at the dose of 0 μg Ni/kg, 7.5 μg Ni/kg, 75 μg Ni/kg and 750 μg Ni/kg, respectively. PM2.5 at the dose of 15 mg/kg contains 7.5 μg Ni. The rats were sacrificed after 24 h of instillation, blood samples were collected and indices of blood coagulation (plasma prothrombin time (PT), plasma-activated partial thromboplastin time(APTT), fibrinogen(Fib), and tissue factor(TF))were measured. Results PT levels in the plasma decreased significantly in PM2.5-treated rats compared with the control group, while there were no changes with APTT. Plasma fibrinogen increased significantly at 15 mg/kg and 30 mg/kg PM2.5 groups. The TF concentrations in plasma increased significantly at 7.5 mg/kg bw PM2.5 group, while the high-dosage groups (15, 30 mg/kg bw groups)only showed slight increase. The PT and APTT showed no changes in NiSO4-treated rats. Plasma fibrinogen levels increased significantly at 750 μg Ni/kg NiSO4-treated rats. The TF concentrations in plasma increased significantly at 75 μg Ni/kg and 750 μg Ni/kg dosage groups (P<0.05), there was a slight increase in low dosage(7.5 μg Ni/kg)group. Conclusion PM2.5 induced changes in blood coagulation function in rats. The administration of NiSO4 to rats induced similar pathological changes caused by PM2.5. This study suggested that NiSO4 may partially contribute to the blood coagulative effects of PM2.5 on rats.
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