气管滴注硫酸镍对大鼠炎症和肺损伤发生的影响

Damage on lung and systemic inflammation induced by nickel sulfate intracheal instillation in rats

目的观察气管滴注硫酸镍对大鼠的急性毒性作用及其机制。方法将28只体重为280～310g的雄性Wistar大鼠随机分为对照组、硫酸镍低、中、高剂量组,根据镍在细颗粒物中的含量,设计镍的染毒剂量分别为7.5、75和750μg/kg。采用一次性气管滴注染毒,24h后处死动物,收集支气管肺泡灌洗液(BALF)进行细胞计数,总蛋白(TP)、乳酸脱氢酶(LDH)和炎性因子(IL-6、TNF-α)的测定;收集血液测定血清中炎性因子(IL-6、TNF-α)、C-反应蛋白(CRP)和镍的水平。结果不同剂量硫酸镍均可引起大鼠BALF中白细胞总数、中性粒细胞数、巨噬细胞显著升高(P<0.01),较高剂量Ni(75和750μg/kg)可引起BALF中TP水平、LDH活力和炎性因子IL-6、TNF-α水平显著增高(P<0.05或P<0.01);硫酸镍染毒24h后,大鼠血清TNF-α水平明显增高,与对照组相比差异有显著性(P<0.05);血清CRP水平随硫酸镍剂量升高而增高,但仅高剂量组差异有显著性(P<0.05)。此外,随着硫酸镍染毒剂量的增加,血清中镍水平也呈现明显的上升趋势。结论硫酸镍气管滴注可引起Wistar大鼠急性肺损伤和全身炎症反应,与含相同剂量镍的PM2.5相比,硫酸镍的作用较弱,提示镍在PM2.5的毒性作用中可能发挥重要作用,但PM2.5中其他成分的作用也不容忽视。

Objective To investigate the acute toxic effects induced by nickel sulfate(NiSO_4) in order to clarify the possible role of nickel in PM_ 2.5 .Methods Twenty-eight male Wistar rats were divided into four groups, NiSO_4 was administered by intratracheal instillation at the doses of Ni 0, 7.5, 75 and 750 μg/kg for 24h respectively. The rats were sacrificed and brochoalveolar lavage fluid (BALF) were collected and analyzed to estimate the injury (total protein (TP) and lactate dehydrogenase (LDH)) and inflammation of lung. Blood were collected and parameters of inflammation (total cell numbers, interleukin-6 (IL-6), tumor necrosis factor (TNF-α)) and CRP were measured. The nickel levels in the blood were also determined. Results NiSO_4 induced significant increases of leukocytes, neuprophil,TP contents and LDH avtivity in BALF(P<0.05, P<0.01).The level of TNF-α and IL-6 in BALF of NiSO_4-treated rats increased significantly compared with those of the control group(P<0.05). The level of TNF-α in blood of NiSO_4-treated rats increased significantly compared with the control group. Concentrations of CRP in the serum were more higher in NiSO_4-treated rats than the control group, but statistical significances were only seen in the highest dosage group (Ni 750 μg/kg). Nickel in serum of NiSO_4-treated rats increased significantly in a dose-dependent manner.Conclusion NiSO_4 induced pulmonary and systemic inflammation effects in rats, suggested that NiSO_4 may play an important role in the acute effects of PM_ 2.5 .