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

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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 investigate the effects of isophorone diisocyanate (IPDI) on serum biochemical parameters of liver and kidney in rats, and to explore its hepatotoxicity and its mechanism, and to provide experimental evidence for the follow-up study. Methods Eighty SPF healthy Wistar male rats aged 4 weeks were randomly divided into 1 / 4LD50, 1 / 8LD50, 1 / 16LD50 and solvent control groups (corn oil) Group of 20, using intraperitoneal injection of IPDI way of exposure, continuous exposure to 13 weeks, 1 day. Weekly exposure to body weight and food intake were measured. Blood samples were taken from the femoral vein of experimental animals 24 h after the last exposure (fasted for 12 h), serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP) (TP), albumin (ALB), globulin (GLB), blood urea nitrogen (BUN), creatinine (Cr), uric acid (UA), nitric oxide synthase (NOS), nitric oxide The concentration of somatostatin C (Cys C). Results Before and after treatment, the body weight, total food intake, kidney weight and organ coefficient of rats in each exposure group were not significantly different from those in the control group (P> 0.05). The liver weight And organ coefficient was significantly lower than the control group (P <0.01). Serum levels of ALT, AST, ALP and GLB in high and middle dose groups were significantly higher than those in control group, and ALB levels in serum were significantly lower than those in control group (P <0.01). There was no significant difference between serum TP and control group P> 0.05). Serum levels of Cr, iNOS and NO in high-dose group were significantly higher than those in control group (P <0.01). The levels of serum Cys C in high and middle dose groups were significantly higher than those in control group (P <0.01). Conclusion IPDI can cause organic damage to the liver and affect the protein synthesis of the liver, but the mechanism of its toxicity is not yet clear. IPDI can cause renal damage, affecting glomerular filtration function, and its mechanism of renal toxicity and NO.
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