斑蝥素引起小鼠急性中毒的器官损伤

目的:通过建立斑蝥素(cantharidin,CTD)诱导小鼠急性毒性模型,比较CTD急性毒性剂量给药后小鼠各器官损伤情况,探究CTD引起小鼠急性毒性的靶向器官及可能机制。方法:取Balb/c小鼠,CTD梯度剂量(2,3,4 mg·kg-1)一次性灌胃给药,观察小鼠的生存状态,并获得CTD急性毒性剂量和最佳取材时间。根据以上结果,以CTD急性毒性剂量给药,3 h后使用戊巴比妥钠对小鼠进行麻醉后检测心电图,取血清检测丙氨酸氨基转移酶、门冬氨酸氨基转移酶、尿素氮、乳酸脱氢酶、肌酸激酶、心肌肌钙蛋白的浓度。取心、肝、肾、肠通过苏木素-伊红(HE)染色进行组织病理学观察分析。结果:与正常组小鼠相比,给药组小鼠不同剂量CTD给药后,小鼠的中毒反应随剂量升高而增大,CTD急性毒性剂量为4 mg·kg-1,平均死亡时间为(4.64±1.33)h。与正常组小鼠相比,CTD组急性毒性剂量给药后小鼠心电图出现异常J点上移,心率趋缓。血清中丙氨酸氨基转移酶、门冬氨酸氨基转移酶、尿素氮、心肌肌钙蛋白均明显升高(P0.05),肌酸激酶、乳酸脱氢酶显著升高(P0.01);HE病理染色显示,与正常组相比,CTD组急性毒性剂量给药后引起小鼠小肠、肝脏、肾脏损伤不明显,心脏出现炎症细胞浸润、心肌纤维结构紊乱,心肌间质充血及点状坏死,损伤严重。结论:心脏是CTD引起小鼠急性毒性关键靶向器官。

Target Organ for Acute Toxicity of Cantharidin

Objective: To explore the target organ for the acute toxicity of cantharidin (CTD) by establishing a cantharidin-inducing acute failure mouse model. Method: Balb/c mice were treated with different doses of cantharidin(2,3,4 mg·kg^-1), and their activities were speculated. After that, the remaining mice were treated with the acute toxic dose by gavage for 3 hours, their blood samples were collected for biochemical analyses, and tissue samples were collected from livers, intestines, kidneys, and hearts for histopathological analyses. For another group,CTD was measured after treatment with 4 mg·kg^-1 cantharidin for 3 h, and animals were anaesthetized with pentobarbital sodium. Result: Compared with the control group, poisoning response of the CTD mice deteriorated with the increase of concentration. The acute toxicity dose of CTD was 4 mg·kg^-1, and the average death time was (4.64±1.33) h. After the administration at the acute toxicity dose, compared with control group,ECG of the mice showed abnormally upward J point and slowdown in heart rate. Cantharidin led to significant increases in the levels of alanine aminotransferase (ALT) (P<0.05), aspartate aminotransferase (AST) (P<0.05), rea nitrogen (BUN) (P<0.05), creatine kinase (CK) (P<0.01), lactate dehydrogenase (LDH) (P<0.01), and cardiac troponin (cTn) (P<0.05). Cantharidin caused inflammatory cell infiltration and myocardial injury in heart. Conclusion: Heart is the target organ of cantharidin at the acute toxic dose. Cantharidin could induce myocardial injury and cardiac structural damage.