环肽α-amanitin在小鼠体内的毒性作用研究

Toxicity of α-amanitin on Mice in vivo

目的研究环肽α-amanitin在动物体内的毒性作用。方法对小鼠尾静脉和腹腔注射给药,确定环肽α-amanitin对小鼠的半数致死量(LD50);研究α-amanitin对小鼠外周血血象和生化指标的影响,脏器指数、组织病理学改变,并定性检测中毒小鼠血液及组织中的α-amanitin。结果腹腔和尾静脉两种给药方式的LD50分别为0.742mg/kg和0.327mg/kg。对小鼠尾静脉注射0.327mg/kgα-amanitin24h后,小鼠白细胞(WBC)、红细胞(RBC)和血红蛋白(Hb)明显降低,同时尿素氮(BUN)和肌酐(Crea)明显增高,谷丙转氨酶、谷草转氨酶、总胆红素和结合胆红素(ALT、AST、TBIL和DBIL)值分别增高至空白对照组的24.0、9.6、26.3和37.0倍;作用48h后,小鼠肝脏和肾脏指数显著增高,细胞核碎裂和组织局灶性坏死,肝脏和肾脏组织中可检出α-amanitin。结论小鼠对α-amanitin毒性作用的敏感血液指标是BUN、Crea、ALT、AST、TBIL和DBIL;肝脏、肾脏是主要受损脏器,α-amanitin作用后期,可以蓄积在肝脏和肾脏。

Objective To study the toxic effect of α-amanitin from Amanita fungi on mice in vivo. Methods The LD50 of α-amanitin was determined with intravenous and intraperitoneal injections of α-amanitin. The mice were then injected intravenously with LD50 dose of α-amanitin, and the viscera index was evaluated. The peripheral blood samples were collected 24 hours later to measure the hemogram and biochemical indicators. The histological changes of internal organs were examined. The α-amanitin in organ tissues were measured. Results The intraperitoneal and intravenous LD50 doses of α-amanitin were 0. 742 mg/kg and 0. 327 mg/kg bodyweight, respectively. The WBC, RBC and Hb decreased significantly, whereas the serum BUN and Crea increased significantly. The serum ALT, AST, TBIL and DBIL increased to 24.0, 9.6, 26.3 and 37.0 times of the levels of controls, respectively, 24 hour after the injection. The viscera indexes of liver and kidney also increased significantly, and focal necrosis was found in the tissue slices 48 hours after the injection. The poison compound α-amanitin was detected in liver and kidney tissue homogenates by RP-HPLC 48 hours after the injection. Conclusion Serum BUN, Crea, ALT, AST, TBIL and DBIL are sensitive indicators for the toxicity of α-amanitin in vivo. The pathological changes of liver and kidney are very serious. The cyelopeptide α-amanitin could reside in the two organs for a long last toxic effect.