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目的研究三氯乙烯(TCE)及其代谢产物三氯乙醇(TCOH)、三氯乙酸(TCA)对豚鼠的皮肤致敏作用,及其致敏豚鼠肝脏功能和结构改变。方法无特定病原体级健康白化Hartley豚鼠106只,分为TCE、TCOH、TCA实验组及溶剂对照组、阳性对照组和空白对照组共8组,用TCE、TCOH和TCA按照豚鼠最大值实验法进行皮肤致敏实验,计算各组致敏率。TCOH、TCA实验组根据皮肤致敏结果分为致敏阴性和致敏阳性亚组。在终末激发24 h后取肝脏、心脏、脾脏、肺和肾脏称质量计算脏器系数,采血检测血清中丙氨酸氨基转移酶(ALT)、γ-谷氨酰转肽酶(γ-GTP)和碱性磷酸酶活力,并对肝脏进行病理学检查。结果 TCE、TCOH和TCA的致敏率分别为80.0%、35.0%和0.0%;TCE致敏率高于TCOH致敏率(P<0.01)。TCE、TCOH实验组中,雌、雄豚鼠致敏率差异均无统计学意义(90.0%vs 70.0%,50.0%vs 20.0%,P>0.05)。TCE致敏阳性亚组分别与空白对照组、TCE溶剂对照组和TCE致敏阴性亚组比较,其肝脏系数均升高[(3.89±0.42)vs(3.30±0.35)、(3.89±0.42)vs(3.47±0.49)、(3.89±0.42)vs(3.42±0.37),P<0.05],ALT活力均升高[(68.86±14.09)vs(45.50±11.39)、(68.86±14.09)vs(46.06±10.13)、(68.86±14.09)vs(47.56±12.10)μmol/(min·L),P<0.05],γ-GTP活力均升高[(22.19±6.86)vs(12.92±5.37)、(22.19±6.86)vs(12.29±2.98)、(22.19±6.86)vs(12.84±6.70)μmol/(min·L),P<0.01]。TCOH致敏阳性亚组分别与空白对照组、TCOH溶剂对照组和TCOH致敏阴性亚组比较,其ALT活力均升高[(59.86±12.55)vs(45.50±11.39)、(59.86±12.55)vs(44.10±4.79)、(59.86±12.55)vs(43.61±9.07)μmol/(min·L),P<0.05],γ-GTP活力均升高[(16.83±4.96)vs(12.92±5.37)、(16.83±4.96)vs(12.71±5.59)、(16.83±4.96)vs(13.36±2.46)μmol/(min·L),P<0.05]。TCE致敏阳性亚组ALT、γ-GTP活力分别高于TCOH致敏阳性亚组[(68.86±14.09)vs(59.86±12.55)、(22.19±6.86)vs(16.83±4.96)μmol/(min·L),P<0.05]。病理检查显示TCE致敏阳性亚组和TCOH致敏阳性亚组肝细胞均可见局灶性坏死及坏死组织周围炎性细胞浸润,TCE致敏阳性亚组还可见肝窦Kupffer细胞增多。结论 TCE是强致敏物,TCOH为中度致敏物,TCA未见致敏作用。TCE、TCOH致敏阳性的豚鼠体内发生了肝脏功能障碍和结构的破坏。
Objective To study the skin sensitization of trichlorethylene (TCE) and its metabolites trichloroethanol (TCOH) and trichloroacetic acid (TCA) to guinea pigs and the functional and structural changes of liver in sensitized guinea pigs. Methods A total of 106 healthy albino Hartley guinea pigs without specific pathogen were divided into 8 groups: TCE, TCOH, TCA experimental group, solvent control group, positive control group and blank control group. TCE, TCOH and TCA were used according to the maximum experimental value of guinea pig Skin sensitization test, calculate the sensitization rate of each group. TCOH, TCA experimental group according to skin sensitization results divided into sensitized negative and sensitized positive subgroups. The liver, heart, spleen, lungs and kidneys were collected at the end of 24 h and the organ coefficient was calculated. Serum alanine aminotransferase (ALT) and γ-glutamyl transpeptidase (γ-GTP ) And alkaline phosphatase activity, and pathological examination of the liver. Results The sensitivities of TCE, TCOH and TCA were 80.0%, 35.0% and 0.0%, respectively. The sensitization rate of TCE was higher than that of TCOH (P <0.01). TCE, TCOH experimental group, the sensitivities of female and male guinea pigs showed no significant difference (90.0% vs 70.0%, 50.0% vs 20.0%, P> 0.05). The TCC sensitization positive subgroups had higher liver coefficient than the blank control group, TCE solvent control group and TCE sensitized negative subgroup respectively (3.89 ± 0.42 vs 3.30 ± 0.35 vs 3.89 ± 0.42 vs (3.47 ± 0.49), (3.89 ± 0.42) vs (3.42 ± 0.37), P <0.05]. ALT activity was significantly higher than that of the control group (68.86 ± 14.09 vs 45.50 ± 11.39 vs 68.06 ± 14.09 vs 46.06 ± (22.19 ± 6.86) vs (12.92 ± 5.37), (22.19 ± 6.86) vs (47.8 ± 14.9 vs 47.56 ± 12.10μmol / (min · L), P <0.05] 6.86) vs (12.29 ± 2.98), (22.19 ± 6.86) vs (12.84 ± 6.70) μmol / (min · L), P <0.01. TCOH-sensitized positive subgroups had higher ALT activity compared with blank control group, TCOH solvent control group and TCOH sensitized negative subgroup [(59.86 ± 12.55) vs (45.50 ± 11.39) vs (59.86 ± 12.55 vs (44.10 ± 4.79), (59.86 ± 12.55) vs (43.61 ± 9.07) μmol / (min · L), P <0.05] (16.83 ± 4.96) vs (12.71 ± 5.59), (16.83 ± 4.96) vs (13.36 ± 2.46) μmol / (min · L), P <0.05. The activities of ALT and γ-GTP in TCE positive group were significantly higher than those in TCOH positive group [(68.86 ± 14.09) vs (59.86 ± 12.55), (22.19 ± 6.86) vs (16.83 ± 4.96) μmol / (min · L), P <0.05]. Pathological examination showed that both TCE-sensitized subgroup and TCOH-sensitized subgroup of hepatocytes showed focal necrosis and infiltration of inflammatory cells around the necrotic tissue. The number of hepatic sinusoid Kupffer cells also increased in TCE-sensitized subgroup. Conclusion TCE is a strong sensitizer, TCOH is a moderate sensitizer, TCA no sensitization. TCE, TCOH-sensitized guinea pigs developed liver dysfunction and structural damage.