拔毒生肌散中汞成分在大鼠体内的蓄积情况研究

目的:观察中药外用制剂拔毒生肌散(BDSJS)中汞成分在破损皮肤大鼠体内的蓄积情况。方法:破损皮肤大鼠连续涂敷BDSJS 4周,分别在给药4周及停药4周测定血液、尿液、肾脏中汞的含量;测定大鼠的尿β-N-乙酰氨基葡萄糖苷酶、β2-微球蛋白含量、肾功和肝功等血生化指标、凝血酶原时间及活化部分凝血活酶时间,并观察肾等脏器的组织形态。结果:给药4周,低、中、高剂量组大鼠的血汞、尿汞、肾汞含量均明显升高;停药4周,低、中、高剂量组大鼠尿汞含量分别下降89%,78%,93%,肾汞含量分别下降55%,51%,57%,血汞含量基本恢复到正常水平。BDSJS对肾脏的影响最明显。高剂量组大鼠的肾脏系数、尿β2-微球蛋白含量明显升高,可见2只大鼠出现肾小管上皮细胞肿胀;停药4周,肾脏系数、尿β2-微球蛋白及肾脏的组织形态变化基本恢复正常。结论:BDSJS连续给药4周可导致汞成分在血液和肾脏中的蓄积,主要蓄积在肾脏。当肾脏中的汞成分达到一定量时,可对肾小管上皮细胞造成损伤。BDSJS 2.2 mg.cm-2可造成肾小管的轻度损伤,但其损伤是可逆性的,停药4周后可基本恢复,1.1 mg.cm-2为安全剂量。

Study on mercury accumulation in rats induced by Badu Shengji San

Objective: To study the mercury accumulation in injured skin rats induced by Badu Shengji San(BDSJS),a traditional Chinese medicine preparation for external use.Method: Injured skin rats were treated with BDSJS for consecutively 4 weeks.During the 4 weeks and the following 4 weeks after the drug withdrawal,samples were collected for determining mercury contents in blood,urine and kidney,with urinary N-acetyl-β-D-glucosaminidase(NAG)and β2-microglobulin(β2-MG)as indicators of renal toxicity and serum biochemical indicators of hepatic and renal functions.Additionally,activated partial thromboplastin time(APTT),prothrombin time(PT) and kidney and renal pathological changes were also observed.Result: Compared to injured skin rats,mercury contents of blood,urine and kidney were increased significantly in low,middle and high-dose BDSJS groups administered for consecutive 4 weeks.The levels of mercury showed decreases in urine(89%,78%,93%) and kidney(55%,51%,57%),and blood mercury concentration recovered to the normal range in low,middle and high-dose BDSJS groups after the drug withdrawal for 4 weeks.Kidney coefficient and β2-MG were remarkably increased and renal tubular epithelial cell swelling could be found in the high-dose group,and kidney coefficient,β2-MG and renal morphology basically recovered to the normal levels after the drug withdrawal for 4 weeks.Conclusion: The administration of BDSJS for consecutively 4 weeks can cause mercury accumulation in blood and mainly in kidney.Once the accumulated mercury concentration of kidney reaches a certain level,renal tubular epithelial cells would be injured.1.1 mg·cm-2 of BDSJS is proved to be safe and 2.2 mg·cm-2 can cause mild but reversible injury in the function of kidney which can be recovered after drug withdrawal for 4 weeks.