CAJ | 학술논문

目的研究青藤碱在大鼠体内的分布、蓄积与脏器毒理的关系,为青藤碱制剂的临床合理用药提供药理学和毒理学依据。方法采用以青藤碱150 mg*kg-1*d-1 ip，连续给药6 wk，以及给药6 wk后停药1 wk 三种给药方案，分别取大鼠血及各重要器官，用HPLC法测定青藤碱在体内脏器的浓度，同时进行脏器组织切片及血液生化指标等检查。结果一次给药，或多次给药，脏器药物含量均以肝脏为高，其次为心、肾、肺、脑。停药1 wk后脏器药物含量均低于可检测浓度。肝组织切片表明所用剂量的青藤碱对肝细胞有一定的影响，主要表现为细胞肿胀，肝窦消失，但对肝功能无明显损害。青藤碱也可引起心肌轻度充血，但未见明显心肌病理改变。连续给药6 wk睾丸中未检出青藤碱，且睾丸组织学检查无明显改变，但可降低精子活力、死精增加，与体外实验结果类同，停药1 wk后可基本恢复。结论青藤碱一次或多次给药脏器分布浓度依次为肝、心、肾、肺、脑、睾丸中未检出。组织切片表明药物对肝细胞有轻度影响，对其他脏器影响甚少。
목적연구청등감재대서체내적분포、축적여장기독리적관계,위청등감제제적림상합리용약제공약이학화독이학의거。방법채용이청등감150 mg*kg-1*d-1 ip，련속급약6 wk，이급급약6 wk후정약1 wk 삼충급약방안，분별취대서혈급각중요기관，용HPLC법측정청등감재체내장기적농도，동시진행장기조직절편급혈액생화지표등검사。결과일차급약，혹다차급약，장기약물함량균이간장위고，기차위심、신、폐、뇌。정약1 wk후장기약물함량균저우가검측농도。간조직절편표명소용제량적청등감대간세포유일정적영향，주요표현위세포종창，간두소실，단대간공능무명현손해。청등감야가인기심기경도충혈，단미견명현심기병리개변。련속급약6 wk고환중미검출청등감，차고환조직학검사무명현개변，단가강저정자활력、사정증가，여체외실험결과류동，정약1 wk후가기본회복。결론청등감일차혹다차급약장기분포농도의차위간、심、신、폐、뇌、고환중미검출。조직절편표명약물대간세포유경도영향，대기타장기영향심소。
AIM　To investigate the relationship between sinomenine distribution and its organic toxicology in rats so as to give some pharmacological data for clinical application of sinomenine. METHODS　Three kinds of administration plans were designed in the experiment, ie sinomenine was ip administered at the dosage of l50 mg*kg-1 per day, repreat-dosed for 6 wk and suspended the drug for 1 wk after 6wk repeat-doses．At the end of the each administration plan，the animals were sacrificed and their blood and their main internal organs were collected for the purpose of measurement of sinomenine concentration in each sample by HPLC. Meanwhile，the histopathological and serological examinations were also done in the experiments. RESULTS　The sinomenine concentration in rats internal organs were in order of liver, heart, lung and brain either in single-dosed treated animals or in repeat-dosed treated animals for 6 wk. However，the concentration of sinomenine could not be detected by HPLC after l wk drug-suspension，the histopathological examination showed that sinomenine at the dosage of l50 mg*kg-l per day for 6wk treatment could slightly damage liver ce11s, dominant1y caused the cell edema，but no any influence on the sero1ogy of liver and kidney. Sinomenine ip could also cause a mild hyperaemia of the rats heart tissues but no any histopathological changes had been observed. In testis tissues no sinomenine had beed detected although the animals were treated by repeat treatment for 6 wk and no any histopathological changes had been found yet. However, Sinomenine could partialy inhibit the sperm vitalities and amount of the dead sperms were a1so augmented. It was similar to in vitro eperiments. These influences of sinomenine on testis could be quickly recovered by drug suspension. CONCLUSION　Sinomenine concentration were in order of liver, heart, kidney, lung and brain either in treatment by single dose or by repeat-dose administration. The histopathological changes were only abserved in liver cells of the animals which indicates that it should be in consideration of the liver functions during treatment course of the drug.