异佛尔酮二异氰酸酯对大鼠肝肺的氧化损伤及对体液免疫的影响

Effect of isophorone diisocyanate on oxidative damage to liver and lung and humoral immunity of rats

目的探讨异佛尔酮二异氰酸酯(IPDI)对大鼠肝、肺的氧化损伤作用,研究其对体液免疫的影响及其可能机制,为后续研究提供实验依据。方法选择健康SPF级Wistar雄性大鼠80只,随机分为高剂量(1/4LD50)、中剂量(1/8LD50)、低剂量(1/16LD50)组和溶剂对照组(玉米油),每组20只,采用腹腔注射IPDI的方式进行染毒,连续染毒13周,每天1次。于末次染毒后24 h,对清醒状态下的实验动物进行眼眶静脉采血,测定血清中免疫球蛋白Ig G、Ig A、Ig M、Ig E和补体C3、C4的含量。然后将全部实验动物断头处死,测定肝脏、肺脏组织中超氧化物歧化酶(SOD)、过氧化氢酶(CAT)、谷胱甘肽过氧化物酶(GSH-Px)的活力以及丙二醛(MDA)的含量。结果高、中剂量组大鼠肝脏SOD、CAT、GSH-Px活力均明显低于对照组(均P<0.01);高、中剂量组大鼠肝脏MDA含量明显高于对照组(均P<0.01)。高、中、低剂量组大鼠肺脏SOD、GSH-Px活力和高、中剂量组CAT活力均明显低于对照组(均P<0.01);高、中剂量组大鼠肺脏MDA含量均明显高于对照组(均P<0.01)。高剂量组大鼠血清Ig G、Ig M含量和高、中剂量组Ig A、C3含量均明显低于对照组(均P<0.01)。结论 IPDI可产生氧自由基,引起肝脏、肺脏组织的氧化损伤,并可导致免疫球蛋白Ig G、Ig A、Ig M和补体C3水平下降,抑制大鼠体液免疫,但其机制仍需进一步研究。

[Objective]To evaluate the oxidative damage caused by isophorone diisocyanate （IPDI） in liver and lung of rats, study the effect of IPDI on humoral immunity and its possible mechanism, and provide experimental basis for further research. [Methods]80 healthy SPF male Wistar rats were randomly divided into the high-dose （1/4 LD50）, medium-dose （1/8 LDs0） and low-dose（ 1/16 LDso） exposure groups, and a solvent control group（maize oil）, 20 rats in each group. Experimental animals were treated with IPDI by intraperitoneal injection for continuous 13 weeks, once a day. Blood samples were obtained from orbital veins after the last exposure, to determine the concentrations of serum immune globulin （IgG, IgA, IgM and IgE） and complement （C3 and C4）. Rats were killed by decapitation, and the activities of SOD, CAT and GSH-Px, as well as the concentration of MDA in liver and lung tissue were determined.[Results]The activities of SOD, CAT and GSH-Px of liver in high- dose and medium-dose exposure groups were significantly lower than those in control group （all P〈0.01 ）, and the MDA concentration of liver in high-dose and medium-dose exposure groups were significantly higher than that in control group （all P〈0.01 ）. The activities of SOD and GSH-Px of lung in three exposure groups and the activities of CAT of lung in high-dose and medium-dose exposure groups were significantly lower than those in control group （all P〈O.01 ）, and the MDA concentration of lung in high-dose and medium-dose exposure groups were significantly higher than that in control group （all P〈0.01 ）. The concentrations of serum IgG and IgM in high-dose exposure group and the concentrations of IgA and C3 in high-dose and medium-dose exposure groups were significantly lower than those in control group （allP〈0.01 ）.[Conclusion]IPDI exposure could cause oxidative damage to liver and lung tissue by producing oxygen free radicals, result in a diminished output of globulin IgG, IgA lgM and complement C3, and inhibit the humoral immunity of rats, but its mechanism still needs further research.