基于“以药制药”理念探讨甘草制对细辛毒效的影响

Exploration on the Effect of Liquorice Processing on Toxicity and Efficacy of Asari Radix et Rhizoma Based on“Medicine Processed by Medicine”Concept

剖析甘草制对细辛毒效的影响,在急性毒性实验中,将130只KM小鼠均分为6个生细辛组、 6个甘草制细辛组、 1个空白对照组,给药1次,观察14 d内动物的一般情况,采用Bliss法计算半数致死量(LD50).在长期毒性实验中,将50只SD大鼠均分为空白对照组、生细辛低/高剂量组、甘草制细辛低/高剂量组,每天1次,连续灌胃给药28 d,观察动物的一般情况,生化分析法检测血丙氨酸氨基转移酶(ALT)、门冬氨酸氨基转移酶(AST)、肌酐(Cr)、尿素氮(BUN)水平,测定肝肾脏器系数,HE染色法检查肝肾组织病理学变化.在抗偏头痛药效实验中,将40只SD大鼠均分为空白对照组、模型组、西比灵组、生细辛组、甘草制细辛组,每天1次,连续灌胃给药7 d,硝酸甘油造模,ELSIA法检测血一氧化氮(NO)、一氧化氮合成酶(NOS)、降钙素基因相关肽(CGRP)和脑5-羟色胺(5-HT)、去甲肾上腺素(NE)水平.毒性实验结果显示:细辛经甘草炮制后,出现毒性的时间延后,LD50增加,对肝肾功能血液生化指标(ALT, AST, Cr和BUN)、脏器系数、病理损伤的影响减弱.抗偏头痛药效实验结果显示:生细辛组与甘草制细辛组大鼠的血NO, NOS, CGRP和脑5-HT, NE水平差异无统计学意义.综上,甘草制可使细辛减毒存效,研究结果可进一步提升细辛临床用药的安全性和有效性.

This work aimed to dissect the effect of liquorice processing on toxicity and efficacy of Asari Radix et Rhizoma(ARR).In the acute toxicity test,130 KM mice were equally divided into 6 raw ARR groups,6 liquorice-processed ARR groups,and 1 blank control group.Mice were intragastrically given drugs once.The general conditions of the mice were observed for 14 days,and the median lethal dose(LD 50)was calculated by the Bliss method.In the long-term toxicity test,50 SD rats were equally divided into blank control group,raw ARR low/high-dose groups,and liquorice-processed ARR low/high-dose groups.Rats were intragastrically given drugs once a day for 28 days.The general conditions of the rats were observed,and blood alanine aminotransferase(ALT),aspartate aminotransferase(AST),creatinine(Cr),and urea nitrogen(BUN)levels of rats were detected by biochemical analysis method.Meanwhile,the coefficients of liver and kidney organs of rats were determined by analytical balance,and the histopathological changes of liver and kidney of rats were examined by HE staining method.In the anti-migraine pharmacodynamic experiment,40 SD rats were equally divided into blank control group,model group,Sibelium group,raw ARR group,and liquorice-processed ARR group.Rats were intragastrically given drugs once a day for 7 days,and nitroglycerin was used to build migraine model.ELISA method was used to detect blood nitric oxide(NO),nitric oxide synthase(NOS),calcitonin gene-related peptide(CGRP),and brain serotonin(5-HT),norepinephrine(NE)levels of rats.The toxicity test results showed that after ARR was processed by liquorice,the time for toxicity manifestation was delayed,and the LD 50 was increased.Meanwhile,the influence of liquorice-processed ARR on blood biochemical indexes(ALT,AST,Cr,and BUN)of liver and kidney function,organ coefficients,and pathological damage of rats was weakened compared to raw ARR.The anti-migraine pharmacodynamic experiment results suggested that there was no significant difference in blood NO,NOS,CGRP and brain 5-HT,NE levels of rats between raw ARR and liquorice-processed ARR groups.In conclusion,liquorice processing can reduce the toxicity and remain the efficacy of ARR.The results of this work can promote the safety and effectiveness of the clinical use of ARR.