生川乌配伍瓜蒌对大鼠长期毒性实验研究

Radix Aconiti Compatibility of Fructus Trichosanthis on Experimental Study of Long-term Toxicity in Rats

目的:观察生川乌配伍瓜蒌对大鼠长期毒性的影响,探讨该反药对配伍与毒性的关系。方法:SD大鼠80只随机分为生川乌单行(RA)0.3 g·kg-1、生川乌与瓜蒌(1∶1)配伍(RAFT)0.3,0.1 g·kg-1生川乌剂量组、空白对照组,每组20只,雌雄各半,连续ig给药30 d,末次给药24 h后,腹主动脉取血,取脏器计算脏器指数,检测心肌酸激酶(CK),乳酸脱氢酶(LDH)、天门冬氨酸氨基转氨酶(AST),丙氨酸氨基转氨酶(ALT)、肾尿素氮(BUN),血清肌酐(Cr)等生化指标,主要组织器官进行病理学检查。余1/3大鼠停药15 d后检测相应指标。结果:各给药组雌性大鼠肾脏系数高于对照组、胸腺系数低于对照组、红细胞数高于对照组(P<0.05),各给药组雌雄大鼠血清AST,ALT,LDH及BUN水平高于对照组(P<0.05或P<0.01),RA组及RAFT 0.3 g·kg-1组雌性大鼠血清Cr水平高于对照组(P<0.05或P<0.01);RA组雌性大鼠AST,LDH水平高于RAFT 0.1 g·kg-1组(P<0.05或P<0.01);RAFT 0.3 g·kg-1组雌性大鼠AST,ALT,Cr,LDH水平及雄性大鼠AST水平高于RAFT 0.1 g·kg-1组(P<0.05或P<0.01)。主要脏器常规HE染色,RAFT 0.3 g·kg-1及RA组大鼠心、肝、肾均有一定程度损伤。恢复期末,RAFT及RA组雌性大鼠血清AST,ALT水平及雄性大鼠血清ALT水平高于对照组(P<0.05,P<0.01),RAFT及RA组AST,ALT水平差异无统计学意义。结论:在所给剂量下,生川乌对大鼠心、肝、肾有明显毒性,RAFT对大鼠心、肝、肾等器官的毒性与RA组比较无明显差异,RA及RAFT对雌性大鼠毒性强于雄性大鼠。

Objective：This study tries to approach the long-term toxicity of Radix Aconiti （RA）combined with Fructus Trichosanthis （FT） in rats,and investigate the relationship between compatibility and toxicity about this anti-drugs.Method：Eighty male and female SD rats were randomly divided into RA 0.3 g ·kg-1,RATF 0.3,=.1 g ·kg-1 and the contrast groups,each group having 10 male rats and 10 female rats.the rats of the drug administered groups received drugs orally with the water extract of RA and RAFT,the oral volume was 5 mL · kg-1,the rats were administered one time a day for 30 days.24 hours later after the last time of drug administration,2/3 of the rats were sampled blood from their abdominal aorta and organs to figure the indexes of organs out,detecting heart creatine kinase （CK）,lactate dehydrogenase （LDH）,liver aspartate aminotransferase （AST）,alanine aminotransferase （ALT）,kidney blood ureanitrogen （BUN）,creatinine （Cr） and other biochemical markers,making the pathological examination for Major tissues and organs.The remaining 1/3 rats were detected the corresponding indicator in the same way 15 days later after stopping drug administration.Result：The kidney index of female rats in every drug administered groups was higher than contrast group＇s and the thymus index was lower.The RBC were higher than the contrast group （P 〈 0.05）.The AST,ALT,LDH and BUN of each drug administered group were higher than the contrast group （P 〈 0.05,P 〈 0.01）,and the Cr of female rats was higher than the contrast group in RA 0.3 g ·kg-1 and RAFT 0.3 g ·kg-1 groups （P 〈0.05,P 〈0.01）.The AST,LDH of female rats in RA 0.3 g ·kg-1 group were higher than ARTF 0.1 g ·kg-1 group （P 〈 0.05,P 〈0.01）.The AST,ALT,Cr,LDH of female rats and the AST of male rats in RAFT 0.3 g ·kg-1 group were higher than RAFT 0.1 g ·kg-1group （P 〈0.05,P 〈0.01）.A certain extent visceral injury can be seen in heart,liver,and kidney of the rats in RAFT 0.3 g ·kg-1 group through main viscera conventional HE dying.The AST,ALT of female rats and the ALT of male rats in RA 0.3 g · kg-1 and RAFT 0.3 g · kg-1 group were higher than contrast group at the end of recovery term.The differences of AST,ALT in AR group and ARTF group were not statistically significant.Conclusion：Radix Aconiti has significant toxicity in heart,liver and kidney of rats in the given dose.The long-term toxicity has no obvious difference between RA group and RAFT group in rats,but more harmful in female rats than in male.