拔毒生肌散中汞成分在大鼠体内的蓄积情况研究

Study on mercury accumulation in rats induced by Badu Shengji San

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。

Objective： To study the mercury accumulation in injured skin rats induced by Badu Shengii 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 （AFFF） , 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.