目的 研究大黃酸對大鼠ig高劑量對乙酰氨基酚代謝、排泄的影響，闡述大黃酸對藥物性肝損傷的保護(hù)作用及其機(jī)制。方法 將SD大鼠隨機(jī)分為對乙酰氨基酚組（2.5 g/kg）和對乙酰氨基酚（2.5 g/kg）聯(lián)用大黃酸組（125 mg/kg），分別采集兩組大鼠血漿、尿液和糞便樣品，測定對乙酰氨基酚的體內(nèi)藥物濃度，比較對乙酰氨基酚單用組和聯(lián)用大黃酸后對乙酰氨基酚的體內(nèi)藥物濃度差異。結(jié)果 對乙酰氨基酚聯(lián)合大黃酸后對乙酰氨基酚的藥動(dòng)學(xué)行為較單用組有明顯改變。與單用比較，聯(lián)用組對乙酰氨基酚的AUC、C_max均有明顯降低。尿糞排泄的結(jié)果顯示對乙酰氨基酚主要以原型、葡萄糖醛酸結(jié)合物和硫酸結(jié)合物的形式從尿液排泄，48 h內(nèi)聯(lián)用組的原型、葡萄糖醛酸結(jié)合物和硫酸結(jié)合物的尿糞排泄量要高于單用組，表明大黃酸能夠促進(jìn)對乙酰氨基酚的排泄速率。結(jié)論 大黃酸可以顯著影響高劑量對乙酰氨基酚的藥動(dòng)學(xué)行為，通過增加對乙酰氨基酚的排泄而降低對乙酰氨基酚在體內(nèi)的暴露，從藥動(dòng)學(xué)的角度闡釋大黃酸對藥物性肝損傷的保護(hù)作用。

Objective To study the effects of rhein on metabolism and excretion in rats ig high-dose acetaminophen, and to elucidate the protective mechanism of rhein on drug-induced liver injury. Methods SD rats were randomly divided into paracetamol group (2.5 g/kg) and combination of paracetamol (2.5 g/kg) with rhein (125 mg/kg) group. The plasma, urinary and excreta samples were collected to determine the concentrations of paracetamol. Then compare the difference of the concentration of paracetamol in the paracetamol alone and combination with rhein group. Results Pharmacokinetic parameters of paracetamol combined with rhein were significantly different with thoset in the single group. Compared with paracetamol alone, the AUC and C_max of paracetamol in combination group were significantly decreased. Urinary and fecal excretion results showed that paracetamol was mainly excreted in urine in the form of prototypes, glucuronide conjugates, and sulfuric acid conjugates. The urinary and fecal excretion of paracetamol prototypes, glucuronide conjugates, and sulfuric acid conjugates in the combination with rhein group were significantly higher than those in the single administration group in 48 h, indicating that the urinary and fecal excretion rate of acetaminophen was increased after administration of rhein. Conclusion Rhein can significantly affect the pharmacokinetics of paracetamol, and reduce the exposure of acetaminophen in vivo by increasing the excretion of paracetamol, elucidating its hepatoprotective role from pharmacokinetic perspective.

國家自然科學(xué)基金青年項(xiàng)目資助（81302839）