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目的:比较朱砂及万胜化风丹与氯化汞、甲基汞的亚急性毒性作用。方法:健康SD大鼠连续每天分别灌胃万胜化风丹(0.42 g.kg-1)、朱砂(0.15 g.kg-1)、硫化汞(0.15 g.kg-1)、氯化汞(0.02 g.kg-1)、甲基汞(0.001 g.kg-1),以及生理盐水21 d,观察大鼠一般情况,监测体重,于末次给药后断头取血、肝脏、肾脏和脑组织,计算肝、肾指数,检测血清谷丙转氨酶、尿素氮、肌酐含量,检测肝、肾、脑组织中汞蓄积量,RT-PCR法检测肝脏金属硫蛋白-1(MT-1)、细胞色素P450基因亚型(Cyp1a1,Cyp2b1,Cyp2e1,Cyp3a2,Cyp4a10)mRNA的相对表达量。结果:氯化汞引起大鼠体重明显低于对照组,肝、肾汞蓄积量明显增多;甲基汞显著地引起大鼠肝、肾、脑组织中汞蓄积量增多;而万胜化风丹和朱砂组没有明显变化。然而,各组血液生化和组织病理学没有表现出显著差异。氯化汞和甲基汞均明显诱导大鼠肝脏MT-1 mRNA的表达。万胜化风丹、朱砂引起肝Cyp3a2 mRNA表达增加,而氯化汞和甲基汞抑制了Cyp2e1 mRNA的表达。结论:万胜化风丹以临床等效剂量灌胃大鼠3周,对大鼠的亚急性毒性作用远低于氯化汞、甲基汞。
OBJECTIVE: To compare the subacute toxicity of cinnarin and Wansheng Huadan with mercuric chloride and methylmercury. Methods: Healthy Sprague-Dawley rats were treated with Wansheng Fufeng Dan (0.42 g.kg-1), Cinnabar (0.15 g.kg-1), Mercuric Sulfide (0.15 g.kg-1), Mercuric Chloride 0.02 g · kg-1), methylmercury (0.001 g · kg-1), and normal saline for 21 days. The general condition of the rats was observed, body weight was monitored, blood samples were taken after the last administration, liver, kidney and brain The levels of liver ALT, ALT, creatinine and serum creatinine in liver, kidney and brain tissue were detected by RT-PCR. The levels of MT-1, The relative expression level of P450 gene subtype (Cyp1a1, Cyp2b1, Cyp2e1, Cyp3a2, Cyp4a10) mRNA. Results: The body weight of rats induced by mercuric chloride was significantly lower than that of the control group, and the accumulation of mercury in liver and kidney was significantly increased. Methylmercury significantly increased the accumulation of mercury in liver, kidney and brain of rats, And cinnabar group did not change significantly. However, no significant differences in blood biochemistry and histopathology were shown for each group. Both mercuric chloride and methylmercury significantly induced MT-1 mRNA expression in rat liver. Wansheng Huadan Dan, cinnabar caused liver Cyp3a2 mRNA expression increased, while mercuric chloride and methylmercury inhibited Cyp2e1 mRNA expression. CONCLUSION: Wansheng Huadan Dan was administered to rats at a clinical equivalent dose for 3 weeks. The subacute toxicity to rats was much lower than that of mercuric chloride and methylmercury.