目的 探討朱砂、含朱砂制劑（柏子養(yǎng)心片）及甲基汞對大鼠的體內(nèi)外毒性，為其臨床安全用藥提供科學依據(jù)。方法 ①對比甲基汞、朱砂及柏子養(yǎng)心片體外對人肝HL-7702細胞和人腎近曲小管上皮HK2細胞的毒性，計算半數(shù)抑制濃度（IC₅₀）。②SD大鼠隨機分為對照組，朱砂組0.1 g/kg，柏子養(yǎng)心片0.2、0.4、0.8 g/kg組，甲基汞組0.001 g/kg，每天ig 1次，連續(xù)給藥90 d后，取血及肝、腎組織；試劑盒法檢測血清中丙氨酸轉(zhuǎn)氨酶（ALT）、天冬氨酸轉(zhuǎn)氨酶（AST）、肌酐（CREA）、尿素氮（BUN）水平，測汞儀固體直接進樣法檢測肝、腎組織中汞蓄積量，并對大鼠肝臟和腎臟做組織病理學檢查。結果 體外試驗表明，朱砂、柏子養(yǎng)心片及甲基汞對HL-7702細胞的IC₅₀分別為7.852、6.035、0.009 5 g/L；對HK2細胞的IC₅₀分別為6.297、4.484、0.008 9 g/L。亞慢性毒性試驗表明，甲基汞組大鼠肝、腎組織中汞蓄積量及血清中ALT、AST、CREA、BUN值均顯著高于對照組，而朱砂及柏子養(yǎng)心片（高、中、低劑量）組與對照組比較均沒有顯著性差異；甲基汞組大鼠肝臟呈現(xiàn)肝細胞變性，腎臟可見明顯腎小管損傷，而朱砂及柏子養(yǎng)心片（高、中、低劑量）組與對照比較沒有明顯差異。結論 朱砂及柏子養(yǎng)心片的體內(nèi)外毒性均顯著低于甲基汞，在目前藥典規(guī)定的臨床用量下使用安全性較好。

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.

湖南省自然科學基金項目（2016JJ6078）