豚鼠三氯乙烯中毒性肝损伤的作用剂量研究

Research on the dosages of toxic liver injury induced by trichloroethylene in guinea pigs

目的掌握三氯乙烯(TCE)引起中毒性肝损伤的作用剂量。方法①取FMMU白化豚鼠25只,随机分成5组,每组5只,分别皮内注射TCE0、167、500、1500、4500mg/kg,48h后处死动物取血清分析丙氨酸转氨酶(ALT)、天冬氨酸转氨酶(AST)、总蛋白(TP)、白蛋白(ALB)、球蛋白(GLB),取肝脏观察病理变化;②取FMMU白化豚鼠12只,随机分成2组,分别涂皮TCE0、900mg/kg,48h后处死动物,处理同上。结果与对照组(0mg/kg)相比,皮内注射TCE48h后4500mg/kg组的ALT、AST均升高(P<0.01),TP、GLB下降(P<0.05);1500mg/kg组AST升高(P<0.05)。4500mg/kg组动物均见明显的肝细胞脂肪变性,部分动物肝窦扩张,并见炎细胞浸润,肝细胞局灶性坏死;1500mg/kg组个别动物血管周围肝窦轻度扩张。与对照组比较,TCE900mg/kg涂皮组的观察指标未见显著异常。结论TCE皮内注射剂量低于500mg/kg,涂皮剂量低于900mg/kg时,都不会导致明显的肝损伤。TCE急性中毒性肝损伤病理学变化以脂肪变性为主。

Objective To study the dosages of toxic liver injury induced by tfichloroethylene （TCE） in guinea pigs. Methods （1）Intradermal exposure. 25 female FMMU guinea pigs were equally divided into 5 groups randomly and treated （ intraderreal injection, id） with TCE dissolved in olive oil at the doses of 0, 167,500, 1 500 and 4 500 mg/kg, respectively. （2）Skin direact exposure. 12 FMMU guinea pigs were equally divided into 2 groups and patched with TCE mixed in vaseline at the doses of 0 and 900 mg/kg, respectively. All of the guinea pigs were sacrificed at 48 hours after the injection or patches respectively. Serum alanine transaminase （ALT）, aspartate aminotronsferase （AST）, total protein （TP）.albumin （ALB） and globulin （GLB） as well as liver pathological examination were analyzed. Results Compared with the 0 mg/kg （control） group, ALT and AST increased （ P 〈 0.01 ） , TP and GLB decreased （P 〈 0.05 ） at 4 500 mg/kg group, AST increased （ P 〈 0.05） at 1 500 mg/kg group. Evident fatty degeneration, hepatic sinusoid dilation and inflammatory cell infiltration were observed in the animals of 4 500 mg/kg group. The hepatic sinus around the central veins enlarged in an animal of 1 500 mg/kg group. Compared with the control group, no significant difference was found in the analyzed indexes in animals with TCE skin exposure at 900 mg/kg. Conclusion It is suggested that TCE should not significantly damage the liver below the dosages of 500 mg/kg （id） and 900 mg/kg （ skin patch） , respectively.