硬金属粉尘染毒大鼠外周血和肺脏细胞因子研究

Study of cytokines in peripheral blood and lung of rats exposed to hard metal dust

目的研究大鼠硬金属肺病(HMLD)进展不同阶段肺泡灌洗液(BALF)和血清中细胞因子的动态变化情况。方法于2019年03月,将大鼠随机分为6组,每组8只,生理盐水组(C组)和硬质合金粉染毒组(HM组)各3组。HM组用肺部气管雾化滴注给药套装给予10 mg/只硬质合金粉。染毒4、8和12周取BALF及血清进行基质金属蛋白酶-1(MMP-1)、金属蛋白酶组织抑制因子-1(TIMP-1)和肿瘤坏死因子-α(TNF-α)的酶联免疫吸附试验(ELISA)。结果C组和HM组大鼠各染毒时间行为活动、饮食和皮毛无异常,两组大鼠体重差异无统计学意义(P>0.05)。与C组比较,HM组大鼠BALF中MMP-1水平在染毒4、8和12周明显升高(P<0.05),TIMP-1水平在染毒8和12周明显升高(P<0.05)。而两组间血清中MMP-1和TIMP-1水平在各染毒时间点差异无统计学意义(P>0.05)。C组和HM组大鼠BALF和血清中TNF-α水平在各染毒时间比较,差异均无统计学意义(P>0.05)。结论MMP-1和TIMP-1的动态变化趋势为筛选HMLD诊断和监测潜在的生物标志物提供依据。

Objective To study the dynamic changes of cytokines in bronchoalveolar lavage fluid(BALF)and serum of hard metal lung disease(HMLDR)rats.Methods In March 2019,the rats were randomly divided into 6 groups,each group included 8 rats:control(C)group include 3 groups,hard metal(HM)group include 3 groups.10 mg HM were administered in HM group by using the pulmonary endotracheal tube.After 4,8 and 12 week,the BALF and serum were collected for the enzyme-linked immunosorbent assay(ELISA)of matrix metalloproteinase-1(MMP-1),tissue inhibitor of metalloproteinase-1(TIMP-1)and tumor necrosis factor-alpha(TNF-α).Results There was no abnormality in behavior,diet and fur of rats in C and HM group at each exposure time.There was no significant difference in body weight between the two groups of rats(P>0.05).Compared with the C group,the expression of MMP-1 in BALF of rats in HM group were significantly higher in all stages(4,8 and 12 weeks after exposure)(P<0.05),the expression of TIMP-1 in BALF of rats in HM group were significantly higher in 8 and 12 weeks after exposure(P<0.05).However,there was no significant difference in serum MMP-1 and TIMP-1 levels between the two groups in each stage(P>0.05).There was no significant difference in TNF-α.level in BALF and serum between C and HM group in all stages(P>0.05).Conclusion Expression of MMP-1 and TIMP-1 in BALF have reference value in the HMLD auxiliary diagnosis.