异佛尔酮二异氰酸酯对大鼠肝肾功能血清生化指标的影响

Effect of isophorone diisocyanate on liver and kidney function and serum biochemical indexes of rats

目的研究异佛尔酮二异氰酸酯(IPDI)对大鼠肝肾功能血清生化指标的影响,探讨其肝肾毒性作用及其机制,为后续研究提供实验依据。方法选择4周龄SPF级健康Wistar雄性大鼠80只,随机分为高(1/4LD50)、中(1/8LD50)、低剂量组(1/16LD50)和溶剂对照组(玉米油),每组20只,采用腹腔注射IPDI方式进行染毒,连续染毒13周,每天1次。染毒期间每周对大鼠体重及摄食量进行测定。于末次染毒后24 h(禁食12 h)对实验动物股静脉采血,测定血清中丙氨酸转氨酶(ALT)、天冬氨酸转氨酶(AST)、碱性磷酸酶(ALP)、总蛋白(TP)、白蛋白(ALB)、球蛋白(GLB)、尿素氮(BUN)、肌酐(Cr)、尿酸(UA)、一氧化氮合酶(NOS)、一氧化氮(NO)及血清胱抑素C(Cys C)的浓度。结果各染毒组大鼠染毒前后体重、染毒期间总摄食量、肾脏重量及脏器系数与对照组相比,差异均无统计学意义(P>0.05);高剂量组大鼠肝脏重量和脏器系数明显低于对照组(P<0.01)。高、中剂量组血清中ALT、AST、ALP、GLB明显高于对照组,ALB明显低于对照组(P<0.01);各染毒组血清中TP与对照组的差异均无统计学意义(P>0.05)。高剂量组血清Cr、i NOS、NO明显高于对照组(P<0.01);高、中剂量组血清中Cys C明显高于对照组(P<0.01)。结论 IPDI可对肝脏造成器质性损伤,并影响肝脏的蛋白合成功能,但毒性作用机制尚未明确。IPDI可造成肾功能损害,影响肾小球滤过功能,其肾脏毒性作用机制与NO有关。

[Objective]To evaluate effect of isopborone diisocyanate （IPDI） on liver and kidney function and serum biochemical indexes of rats, to discuss its toxic action on liver and kidney and related mechanism, and provide experimental basis for follow- up study. [Methods]A total of 80 healthy SPF male Wistar rats （4-week-old） were chosen and randomly divided into high （1/4LD50）, medium （1/8LD50） and low （1/16LD50） exposure groups and a solvent control group （maize oil）, with 20 rats in each group. Experimental animals were treated with IPDI intraperitoneally injection for continuous 13 weeks, once a day. Body weight and food intake were recorded during exposure period. Blood samples were obtained from femoral vein after the last exposure 24 h with fasting 12 h. Serum ALT, AST, ALP, TP, ALB, GLB, BUN, Cr, UA, NOS, NO and Cys C concentrations were determined.[Results]No statistical significances in the body weight before and after IPDI exposure, total food intake during exposure period, and kidney weight and organ coefficient between exposure groups and control group were observed （P〉0.05）. Liver weight and organ coefficient in high exposure group were both decreased compared with control group （P〈0.01）. Concentrations of serum ALT, AST, ALP and GLB in high and medium exposure groups were all increased compared with control group（P〈0.01）, with ALB decreased compared with control group（P〈0.01）. No statistical significances were observed in TP concentrations between exposure groups and control group （P〉0.05）. Concentrations of serum Cr, iNOS and NO in high exposure group and serum Cys C in high and medium exposure groups were all increased compared with control group （P〈0.01）. [Conclusion]IPDI may cause organic damage to liver and interfere with protein synthesis function of liver, but mechanism of which is still undiscovered. IPDI can cause damage to kidney＇s function and affect glomerular filtration function. Mechanism of kidney poisoning by IPDI may be related to NO.