目的 探讨朱砂、含朱砂制剂（柏子养心片）及甲基汞对大鼠的体内外毒性，为其临床安全用药提供科学依据。方法 ①对比甲基汞、朱砂及柏子养心片体外对人肝HL-7702细胞和人肾近曲小管上皮HK2细胞的毒性，计算半数抑制浓度（IC₅₀）。②SD大鼠随机分为对照组，朱砂组0.1 g/kg，柏子养心片0.2、0.4、0.8 g/kg组，甲基汞组0.001 g/kg，每天ig 1次，连续给药90 d后，取血及肝、肾组织；试剂盒法检测血清中丙氨酸转氨酶（ALT）、天冬氨酸转氨酶（AST）、肌酐（CREA）、尿素氮（BUN）水平，测汞仪固体直接进样法检测肝、肾组织中汞蓄积量，并对大鼠肝脏和肾脏做组织病理学检查。结果 体外试验表明，朱砂、柏子养心片及甲基汞对HL-7702细胞的IC₅₀分别为7.852、6.035、0.009 5 g/L；对HK2细胞的IC₅₀分别为6.297、4.484、0.008 9 g/L。亚慢性毒性试验表明，甲基汞组大鼠肝、肾组织中汞蓄积量及血清中ALT、AST、CREA、BUN值均显著高于对照组，而朱砂及柏子养心片（高、中、低剂量）组与对照组比较均没有显著性差异；甲基汞组大鼠肝脏呈现肝细胞变性，肾脏可见明显肾小管损伤，而朱砂及柏子养心片（高、中、低剂量）组与对照比较没有明显差异。结论 朱砂及柏子养心片的体内外毒性均显著低于甲基汞，在目前药典规定的临床用量下使用安全性较好。

Objective To investigate the subchronic toxicity on rats and in vitro toxicity of cinnabar and cinnabar preparation (Baizi Yangxin Tablets, BYT) and methylmercury to provide the scientific basis for safety uses in clinic. Methods ①The toxicity of methylmercury, cinnabar and cinnabar preparation on human liver HL-7702 cells and human renal proximal tubule epithelial HK2 cells were compared and calculate the half inhibitory concentration (IC₅₀). ②SD rats were randomly divided into normal group, cinnabar group (0.1 g/kg), BYT 0.2, 0.4, and 0.8 g/kg groups, methylmercury group 0.001 g/kg. The rats were treated with the cinnabar through oral administration once daily for successive 90 d. Blood, livers, and kidneys of rats were taken out respectively after treatment. The serum levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), creatinine (CREA), and urea nitrogen (BUN) were detected by the reagent box method. The mercury accumulation in liver and kidney tissues was detected by the direct injection of mercury analyzer, and the liver and kidney of rats were examined by histopathology. Results In vitro experiments showed that the IC₅₀ of cinnabar, cinnabar preparation, and methyl mercury on human liver HL-7702 cells were 7.852, 6.035, and 0.009 5 g/L; The IC₅₀ of cinnabar, cinnabar preparation and methyl mercury of HK2 cells in human renal proximal tubule epithelium was 6.297, 4.84, and 0.0089 g/L. Subchronic toxicity test showed that the mercury accumulation of methylmercury group was significantly higher than control group in the liver and kidney tissues and the same as the serum levels of ALT, AST, CREA and BUN. There was no significant difference between cinnabar and the BYT (high-, medium-, and low-dose) compared with control group. Histopathological examination of the liver and kidney of the rats in each group showed that methylmercury group appeared degeneration of liver cells and obvious renal tubular injury, compared with control group, there was no significant difference between cinnabar tablet and BYT (high-, medium-, and low-dose) compared with the control group. Conclusion The toxicity of cinnabar and containing cinnabar preparations (BYT) were significantly lower than methylmercury in vivo and in vitro, indicating that the pharmacopoeia prescribed clinical use of the better safety.

湖南省自然科学基金项目（2016JJ6078）