硫代乙酰胺诱导皮质骨质疏松的新毒性作用研究

The new toxic effect of cortical bone osteoporosis induced by thioacetamide

目的探究硫代乙酰胺(Thioacetamide,TAA)诱导皮质骨质疏松的新毒性作用的产生。方法 36只新西兰大白兔随机分成对照组、腹腔注射不同剂量组;隔天记录实验动物的体重值并进行统计学分析;骨髓细胞微核实验分析骨髓变化;血液生化检测分析肝与肾功能的变化;Masson染色、苏木素-伊红(HE)染色分析实验动物肝、肾和心组织的变化;Micro-CT、骨生物力学检测分析骨密度和骨应力的变化。结果与对照组相比,腹腔注射组体重增加率,差异有统计学意义(P<0. 05)。骨髓微核实验显示,与对照组相比腹腔注射组微核阳性,微核率差异有统计学意义(P<0. 05);血液生化检测显示与对照组相比腹腔注射组总胆汁酸、总胆红素和谷氨酰转肽酶水平差异有统计学意义(P<0. 01);Masson染色、HE染色分析显示,与对照组相比,实验组肝、肾和心组织都有纤维化,且以肝最为明显;Micro-CT、骨生物力学检测显示与对照组相比,腹腔注射组的股骨骨密度与骨应力差异有统计学意义(P<0. 01)。结论 TAA具有可诱导皮质骨质疏松的新毒性作用。

Objective To explore the new toxic effects of Thioacetamide(TAA) on cortical osteoporosis. Methods Thirty-six New Zealand white rabbits were randomly divided into control group and intraperitoneal injection of different dose groups;The body weight of the experimental animals was recorded every other day and statistical analysis was performed;Bone marrow changes in experimental animals were analyzed by micronucleus test of bone marrow cells;Liver and kidney function in experimental animals were analyzed by blood biochemical detection;The histological structures of the liver,kidney and heart tissue of experimental animals were analyzed by Masson staining and HE staining;The bone mineral density and bone stress of experimental animals were analyzed by Micro-CT and bone biomechanical tests. Results The increasing of weight was significantly different between the experimental groups and the control group(P<0. 01);the result of bone marrow micronucleus test showed that the micronucleus of the experimental groups were positive,and the micronucleus rates were higher than those in the control group(P<0. 01);the blood biochemical tests showed that the total bile acid,total bilirubin and γ-glutamyl transpeptidase in the experimental groups were significantly higher than those in the control group(P< 0. 01);the result of Masson staining and HE staining showed that the liver,kidney and heart tissues were all fibrotic in the experimental groups,and the liver was the most obvious;the result of Micro-CT and bone biomechanical examination showed that the bone mineral density and bone stress of femur in the experimental groups were significantly lower than those in the control group(P< 0. 01). Conclusion TAA has a new toxic effect that can induce cortical osteoporosis.