| Objective:In this study,the safety of Mahuang decoction was evaluated by repeated intragastric administration for 90 days in SD rats.To observe the nature and degree of toxic reaction of Mahuang decoction on SD rats,the development and recovery of toxic reaction;determine the toxic dose-effect relationship;determine the toxicity of target organs and damage reversibility;the dose of non-toxic reaction was determined to provide reference for dose design and clinical toxicity monitoring of Mahuang Decoction.Method:120 SPF grade SD rats were selected,half male and half female.They were randomly divided into 4 groups with 30 rats in each group:solvent control group（double distilled water）and 3.0 g·kg-1,6.0 g·kg-1,12.0 g·kg-1 Mahuang decoction group.The medicine was gavaged twice a day,morning and evening once.90 days after administration,withdrawal observation 30 days.The general condition,body weight and food intake of rats were observed.After 90 days of administration and 30 days of withdrawal,abdominal artery blood and urine were collected,and the main organs were extracted.Blood routine,urine routine,coagulation function,serum biochemistry,electrolyte and organ coefficient were measured.Result:1.General changes of rats in each groupDuring the experiment,the appearance,physical signs,behavioral activities and fecal traits of animals in each group were not abnormal.2.Changes of body weight of rats in each groupThere was no significant difference in body weight of rats in each group during administration and withdrawal period（P>0.05）.3.Changes in food intake of rats in each groupDuring the administration of female rats,the food intake of each dose group was lower than that of the control group in the 1th–5th weeks（P<0.05）.During the 10th–13th weeks,the food intake of the high-dose group was lower than that of the control group（P<0.05）.During the administration of male rats,the food intake in the high-dose group was lower than that in the control group（P<0.05）.During the withdrawal of female rats,the food intake in the middle and high dose groups was higher than that in the control group（P<0.05）,and the food intakes in the low dose group was lower than that in the control group（P<0.05）.During withdrawal of male rats,the food intake of high-dose group was significantly higher than that of control group（P<0.05）.4.Changes in organ coefficient of rats in each groupDuring the administration period of female rats,there was no significant difference in organ coefficient among groups（P>0.05）.During the administration of male rats,the liver coefficients of middle dose group and high dose groups was significantly higher than that of the control group（P<0.05）.The kidney coefficient of each dose group was higher than that of the control group（P<0.05）.In the withdrawal period of female rats,the renal coefficient in the medium-dose group was higher than that in the control group（P<0.05）.In the withdrawal period of male rats,the brain coefficient in the middle dose group was significantly higher than that in other groups（P<0.05）.5.Changes in blood routine indexes of rats in each groupDuring the administration period of female rats,there was no significant difference in blood routine indexes between groups（P>0.05）.In the administration period of male rats,MCV in each dose group was higher than that in the control group（P<0.05）.MCHC and RDW-CV in the middle and high dose groups were lower than those in the control group（P<0.05）.MPV of each dose group was lower than that of control group（P<0.05）.PDW of low dose group was lower than other groups（P<0.05）.Reti of high dose group was significantly higher than other groups（P<0.05）.In the withdrawal period,the blood routine indexes of rats in each group were not statistically significant（P>0.05）.6.Changes in coagulation function indexes of rats in each groupThere was no significant difference in coagulation indexes between each group during administration and withdrawal period（P>0.05）.7.Changes in serum biochemical and electrolyte indexes of rats in each groupDuring administration period of female rats,UREA of high dose group was lower than that of control group（P<0.05）.During the administration of male rats,ALT in the low and high dose groups was lower than that in the control group（P<0.05）.GLB in the high-dose group was lower than that in the control group（P<0.05）;TBIL in the high-dose group was higher than that in other groups（P<0.05）;CK in the middle dose group was higher than that in other groups（P<0.05）;UREA and UA in high-dose group were lower than those in other groups（P<0.05）;CHOL in the high-dose group was lower than that in the control group（P<0.05）;TG in medium and high dose groups was higher than that in control group（P<0.05）.In the withdrawal period of female rats,GLB in medium and high dose groups was higher than that in the control group（P<0.05）.GLU in high-dose group was significantly higher than that in other groups（P<0.05）;K+in high dose group was lower than that in control group（P<0.05）.In the recovery period of male rats,ALP in each dose group was lower than that in the control group（P<0.05）.Low dose group K+was lower than other groups（P<0.05）.8.Changes of urine routine indexes in ratsDuring the administration of female rats,there was no significant difference in the urine routine of rats in each group（P>0.05）.Compared with control group,the number of negative results of PRO in low and high dose groups was significantly increased（P<0.05）.During the withdrawal period,there was no significant difference in the urine indexes of rats in each group（P>0.05）.Conclusion:1.Long-term administration of Mahuang Decoction can inhibit the food intake of rats,but it can recover after drug withdrawal.2.Long-term administration of Mahuang decoction can make rat liver and kidney organ coefficient increased.3.Long-term administration of Mahuang Decoction can affect MCV,RDW-CV,MCHC,PDW,MPV and Reti in rat blood,but it can recover after drug withdrawal.4.Long-term administration of Mahuang Decoction can reduce ALT,GLB,UREA,UA and CHOL in serum of male rats,increase TBIL and TG,but it can recover after drug withdrawal;UREA in female rats decreased,but UREA recovered and GLU increased after drug withdrawal.Blood glucose level should be regularly checked.5.Long-term administration of Mahuang Decoction can reduce the level of PRO in rat urine,and has no significant effect on other urine routine indexes. |
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