| Objective:Through the acute toxicity test and long-term toxicity test of Tongbi Jiangu recipe,the safety of Tongbi Jiangu prescription was evaluated,the safe dose range of Tongbi Jiangu prescription was determined,and whether there was toxicity,its manifestation,degree and reversibility were judged.The target organs of the toxicity of the prescription were identified,and whether there was delayed toxicity was determined,so as to provide a safety basis for clinical promotion and preparation of proprietary drugs.Methods:（1）Acute toxicity experiment:twelve Kunming mice of SPF grade（body weight 20±2g,half male and half female）were selected for pre-experiment under the condition of maximum concentration and maximum volume.The results showed that the half lethal dose of Tongbi Jiangu recipe to Kunming mice could not be determined,and the maximum dose experiment was used in the formal experiment.Forty Kunming mice of SPF grade（body weight 20±2g,half male and half female）were randomly divided into Tongbi Jiangu recipe group and control group according to sex.The traditional Chinese medicine group was given intragastric administration according to the maximum concentration of 3.65g crude drug/ml and the maximum administration volume（0.4ml/g body weight）,while the control group was given the same volume of drinking water.Three times of intragastric administration,each time at an interval of 5 hours.On the day of administration,the general performance,toxic reaction and death of Kunming mice were observed in the laboratory.After that,it was observed once a day for 14 days.At the end of the observation period,after all the mice were killed with cervical dislocation,the main organs of the mice were observed with naked eyes,the maximum dose of oral Tongbi Jiangu recipe was calculated,and the multiple relationship between the maximum dose of mice and the common clinical dose in adults was determined.（2）long-term toxicity test:80 SPF SD rats（weight 120±20g,half male and half femal e）were randomly divided into high,middle and low dose groups and control group according to sex and body weight.According to the intragastric volume of 2ml/100g body weight,Tong bi Jiangu recipe was given 77.6g crude drug/kg body weight,38.8g crude drug/kg body wei ght and 19.4g crude drug/kg body weight,respectively.The control group was given the sam e amount of drinking water.The drug was given 6 days a week,once a day for 3 months.The general manifestation,poisoning reaction and death of rats were observed every day.After 3months of intragastric administration,10 rats in each group were randomly selected（half male and half female）.Blood samples were collected from the heart after anesthesia to detect blood routine and blood biochemical indexes.Brain,lung,thymus,heart,liver,kidney（bilateral）,sp leen,stomach,adrenal gland（bilateral）,jejunum,bladder,testis（male bilateral）,uterus（femal e）,ovary（female bilateral）were weighed and organ coefficients were calculated.the above or gans were observed with naked eyes and pathological sections were observed.The remaining rats were given the same operation after stopping intragastric administration for 14 days to eva luate the long-term toxic effect of Tongbi Jiangu recipe.Result:（1）Acute toxicity test:Under the condition of maximum concentration,maximu m volume and intragastric administration of Tongbi Jiangu recipe for 3 times/24 hours,no ob vious acute toxicity and drug death were observed within 2 weeks.the maximum dose was 402.76 g/kg body weight,which was 170.66 times of adult clinical dose.（2）long-term toxicity test:1)The body weight of rats in high-dose Tongbi Jiangu recipe group increased slowly fro m the 4th and 5th week to the end of administration,but recovered within 2 weeks after admin istration,and Tongbi Jiangu recipe could cause hyperactivity and fight and bite in some rats.h igh-dose drug has a certain effect on the mental state of rats at the initial stage,but can recover after several weeks of adaptation.2)During the period of administration,the MCH,MPV and MCHC in the middle and lo w dose groups were significantly higher than those in the blank group（P<0.05）,but there was no significant difference between the middle and low dose groups（P>0.05）,and the H CT in the middle and low dose groups was significantly lower than that in the blank group（P<0.05）.The HGB in the high,middle and low dose groups was significantly higher than tha t in the blank group（P<0.05）,but there was no significant difference among the high,mid dle and low dose groups（P>0.05）.The PLT in the high and middle dose groups was signif icantly higher than that in the blank group（P<0.05）,but there was no significant differenc e between the high and middle dose groups（P>0.05）.The PCT in the low dose group was higher than that in the blank group（P<0.05）,but there was no significant difference in oth er indexes between the traditional Chinese medicine group and the blank group（P>0.05）.3)At the end of the administration period,the concentration of Na+in the middle and low dose groups of Tongbi Jiangu recipe was significantly higher than that in the blank group（P<0.05）,but there was no significant difference between the middle and low dose groups（P>0.05）,while the concentration of Mg2+in the high dose group was significantly higher tha n that in the blank group（P<0.05）.At the end of the recovery period,the P+concentration in the middle dose group of Tongbi Jiangu recipe group was significantly higher than that in t he blank group（P<0.05）,but there was no significant difference in other indexes between the traditional Chinese medicine group and the blank group（P>0.05）.4)The organ coefficients of brain,thymus,heart,lung,liver,spleen,stomach,jejunum,k idney,adrenal gland,uterus,ovary and testis in the high,middle and low dose groups were no t significantly different from those in the control group（P>0.05）.During the administration p eriod,there were 1-2 milky spherical protuberances on the surface of bilateral or unilateral kid neys in all the three dose groups,which were adipose tissue.In the middle dose group 3 in the convalescent stage,there were yellowish-white masses at one end of the bilateral renal parenc hyma of different sizes,hard and tough,invading the kidney about 2 to 3 volume,rich blood v essels on the surface,and pathological examination was suspected to be tumor tissue.The uter ine body of No.21 rats in the middle dose group was significantly thickened and the blood ves sels were abundant.In the middle dose group,the number of microglia in brain tissue increase d and a small number of cortical neurons necrotic.Some of the rats in the traditional Chinese medicine group had a small amount of steatosis of hepatocytes.The female rats in the traditio nal Chinese medicine group had uterine cell necrosis and lymphocyte infiltration.Conclusion:1.In the acute toxicity test of Tongbi Jiangu recipe,there was no acute toxicity when the maximum dose was 402.76g crude drug/kg,which was equivalent to 170.66 times of adult cl inical use.two。.2.Tongbi Jiangu recipe was used at a low dose（19.4g crude drug/kg）for 3 months,and there was no long-term toxicity.3.High dose（77.6g crude drug/kg）could slow down the body weight growth of rats aft er taking it continuously for one month,but it could be recovered after drug withdrawal.The h istomorphology of brain,liver,kidney,thymus,testis,uterus,stomach and jejunum were affec ted by high dose（77.6 g crude drug/kg）and middle dose（38.8 g crude drug/kg）for 3 months. |
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