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目的比较含砷牛黄解毒片、雄黄与其他砷化物的毒性。方法昆明种成年小鼠随机分为9组:牛黄解毒片低、中、高剂量组(60、180和600 mg/kg)、京制牛黄解毒片(600 mg/kg)组、雄黄(600 mg/kg)组、二硫化二砷(As2S2,600 mg/kg)、亚砷酸钠(NaAsO2,As3+,42 mg/kg)、砷酸氢二钠(Na2 HAsO4.7 H2 O,As5+,100 mg/kg)及正常对照组,每组6只。分别一次灌胃给药,8 h后取血及肝、肾组织,检测血清丙氨酸转氨酶(ALT)、天冬氨酸转氨酶(AST)、血尿素氮(UREA)、血肌酐(CREA)水平及肝肾组织病理学变化;原子荧光光谱测定肝肾组织中的砷蓄积量;实时荧光定量PCR检测砷毒性敏感基因金属硫蛋白-1(Metallothionein,MT-1)mRNA的表达。结果 As3+和As5+组肝肾中砷蓄积量显著增加,并伴肝肾功能和病理损伤,且MT-1 mRNA表达明显上调;牛黄解毒片各剂量组和京制牛黄解毒片组的肝肾功能和病理检查与正常对照组相似,未见异常;雄黄和As2S2组仅在肝脏中检测到砷,肝肾轻度病理变化,但明显轻于As3+和As5+组;牛黄解毒片仅高剂量组、雄黄、As2 S2组的肝脏检测到微量的砷,但远低于As3+和As5+组;且未见MT-1 mRNA表达的升高。结论牛黄解毒片、雄黄的急性毒性远小于亚砷酸钠、砷酸氢二钠。砷化物的毒性与其化学价位/可溶性关系密切,不能单用总砷含量评价含砷中成药的毒性。
Objective To compare the toxicity of arsenic-containing bezoar detoxification tablets, realgar and other arsenic compounds. Methods Kunming mice were randomly divided into 9 groups: low, medium and high dose Niuhuangjiedu tablets (60,180 and 600 mg / kg), Beijing Niuhuangjiedu tablets (600 mg / kg) (As 2 S 2,600 mg / kg), sodium arsenite (NaAsO2, As 3 +, 42 mg / kg), and sodium arsenate disodium / kg) and normal control group, 6 rats in each group. The rats in each group were given gavage once a day, and the blood and liver and kidney tissues were taken after 8 h. Serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), blood urea nitrogen (UREA) and serum creatinine And liver and kidney histopathological changes. Atomic fluorescence spectrometry was used to determine arsenic accumulation in liver and kidney tissues. Real-time fluorescence quantitative PCR was used to detect the expression of metallothionein-1 (MT-1) mRNA. Results As3 + and As5 + had a marked increase in the accumulation of arsenic in the liver and kidney, together with liver-kidney function and pathological damage, and the expression of MT-1 mRNA was significantly up-regulated. The liver- The pathological examination was similar to the normal control group, no abnormalities were observed. Real arsenic and liver and kidney were detected only in liver and As2S2 group, but the pathological changes of As2O3 and As5 + Trace amounts of arsenic were detected in the liver of As2 S2 group but much lower than those in As3 + and As5 + groups; and no increase in MT-1 mRNA expression was observed. Conclusion Niuhuangjiedu tablets, realgar acute toxicity is much less than sodium arsenite, disodium arsenate. The toxicity of arsenide is closely related to its chemical value / solubility. The total arsenic content can not be used alone to evaluate the toxicity of arsenic-containing proprietary Chinese medicines.