| BackgroundYang deficiency is one of the common clinical syndromes,involving many kind of diseases,who is also the focus of clinical treatment.Therefore,to explore the Yang deficiency syndrome、formation mechanism and change factors,common laboratory indexes change of Yang deficiency,differences and characteristics of the comparison of different animal model of Yang deficiency and summary and analysis them,for the further development and application of animal model of Yang deficiency,to provide scientific basis for clinical treatment based on syndrome differentiation,which has become one of the hot topics in the basic research of Traditional Chinese Medicine.This is not only the modernization of traditional Chinese medicine,and also is the need for the promotion of Chinese Medicine.In recent years,the antagonism in the eighteen medicinal herbs of Chinese medicine has become one of the modern property theory of the most controversial issues,the focus is mainly concentrated on the incompatibility of rationality,In which the compatibility of aconite and Pinellia as the most widely used.Modern experiment has proved that the theory ofthe antagonism in the eighteen medicinal herbs has its certain basis,but have not consistent among the diffrent experimental results,yet can’t form a unified conclusion.Therefore,to carry out with characteristics of the traditional Chinese medicine theory and related drug research,to explore he eighteen medicinal herbs in prescriptions of the role of regularity and rationality,such as both the dosage and proportion,to carry out with a comprehensive and systematic study on the drug.to understand the conditions that has not be cognited,scientific interpretation of its mechanism and connotation,to guide the clinical reasonable use medicine to the contrary to provide the basis.And for clinical safe,efficient and widespread application of toxic Chinese medicines open new ways.to provide a scientific explanation of the mechanism and connotation of it,provide the basis for the clinical use of these drugs.Open up a new way for the clinical application of toxic traditional Chinese medicine securely、efficiently and extensively.Objective1.Aconite and Pinellia ternate in different compatibility proportion of mice acute toxicity study,calculate the half of the mice mortality(LD50),compared with the different combinations of the general behavior and Viscera indexof mice,provide a reference for the safety of clinical medication.2.Observating pharmacodynamic effects of aconite and Pinellia ternating in different compatibility proportion to Yang deficiency rat model,including on cyclic nucleotide system in rats,the hypothalamus-pituitary-Targeting axis(thyroid,adrenal and gonadal),intestines and stomach function,effect of rat’s heart,liver,kidney,spleen,small intestine tissue and Na~+_K--ATP enzyme activity of different organs of rats pathological changes.Methods1.Mice acute toxicity test of Aconite and Pinellia ternate in different compatibility proportion : The experimental and clinical medication consistent,with oral route of administration,through pre-experiment of mice 0%(not dead)and 100%(death)of roughly dose range,aconite and Pinellia of different proportions of three kinds of decoction of experiments were performed.100 mice were fed for 1 weeks,mice were fasted for 16 h,after weighing were randomly divided into two groups according to the weight.Mice were divided into 10 groups of male and female,aconite: Pinellia 1:2 of low,medium and high dose group,aconite: Pinellia = 1:1 the low,medium and high dose group,Radix Aconiti: Pinellia = 2:1 low,medium and high dose group and control group,10 rats in each group.First the dose,successively intragastric mice were given a different dose of liquid medicine,irrigation stomach after close observation of mouse toxicity reaction,continuous observation for 14 days,recording the middle irrigation service after the spontaneous activity of the mice and behavioral changes,each acute toxicity symptoms of time,to time,symptoms and signs of development or outcome of the process.And record the death situation of mice and characteristics before death,death time of mice and quality,quality of heart,liver,spleen,lung,kidney,brain organs calculated Viscera index,and the dead animals were dissected to observe,record the observed changes and death in the organs of mice with pathology detection.According to the death of each group was calculated by the statistical software LD50.SPSS20.0 software is used for processing and statistical analysis,weighted probit regression method(Bliss method)and 95% confidence interval calculation of LD50 and LD50.2.Aconite and Pinellia combination of Yang deficiency model rats pharmacodynamic studies: take 40 rats adaptive feeding after 1 week were no abnormal after included in the experiment.Randomly divided into 5 groups,each with 8,weighing tag.The 4 group in the daily morning with Hydrocortisone Injection and intragastric administration of rhubarb decoction.17 consecutive days.Fifth groups as healthy control group.The 18 day.On the basis of maintaining the original modeling program invariant based,daily in the morning to give three groups made module respectively by gavage were poured into the stomach with different proportion of aconite and Pinellia combination of water decoction,once a day for 2 weeks.The 1 groups were used as model control group.Last after dosing fasted for a night,the next day to abdominal(0.35ml/100 g weight)of 10% chloral hydrate anaesthesia after abdominal aortic blood,rat heart,liver,spleen,kidney,small intestine,80 DEG C preservation reserve.ELISA Kit Method for detection of rat serum levels of cyclic nucleotide(cAMP / c GMP)content and determine the effect of compatibility of aconite and Pinellia ternata of Yang deficiency model rat nerve endocrine system,T3,T4,TSH,promoting of adrenocorticotrophic hormone(ACTH),cortisol(CORT),promoting adrenal cortical hormone releasing hormone(CRH),testosterone(T),and gastrointestinal function including gastrin and motilin levels and ultra trace of total ATP kit determination of total ATP enzyme activity levels in different tissues of rats.HE staining pathological sections of Yang deficiency and normal rat heart,liver,kidney,spleen,thymus tissue for pathological study.Results1.The Aconite: Pinellia 1:2 group,Radix Aconiti: Pinellia = 1:1,aconite: LD50 = 2:1 of Pinellia group respectively 0.975,1.207 and 166.9.Compared with the control group,the treatment group mice cardiac index increased,with significant difference(P < 0.05);the liver index increased,with significant difference(P < 0.05);spleen index increased,with significant difference(P < 0.05);the index changes of lung,aconite: Pinellia = 2 dose group,Radix Aconiti Lateralis Preparata: Pinellia 1:2 high dose group have significant difference(P < 0.05),other groups showed no obvious change;kidney index increased,with significant difference(P < 0.05);cerebral index increased,with significant difference(P < 0.05).2.Changes of cyclic nucleotide levels in rats: compared with healthy control group,model group,decreased the content of serum cAMP(P<0.05),increased the content of cGMP in serum,there was significant difference(P<0.05),serum cAMP/cGMP ratio decreased,there was a significant difference(P<0.05);compared with the model group,treatment drug serum cAMP content increased there was significant difference(P<0.05);increased the content of cGMP in serum,there was significant difference(P<0.05);serum cAMP/cGMP ratio increased,there was a significant difference(P<0.05);changes in hormone levels of hypothalamus pituitary thyroid axis: compared with the healthy control group,model group decreased serum T3,T4 and TSH content,have significant differences(P<0.05);compared with the model group,treatment after administration of serum T3,T4 and TSH were increased,there was significant difference(P<0.05);Hypothalamus-pituitary-Adrenal axis hormone level change: compared with health control group,model group,the serum CORT,CRH content decreased,with significant difference(P < 0.05);compared with the model group,giving drugs after aconite: Pinellia = 1:1 and aconite: Pinellia = 2:1 group serum CORT levels increased,with significant difference(P < 0.05),aconite: Pinellia 1:2 groups had no significant difference,three to the drug group,serum CRH concentration were significantly rise(P < 0.05);Hypothalamus-pituitary-gonadal axis hormone level changes,and health compared to the control group,model group,the serum testosterone(T)level decreased,with significant difference(P < 0.05);compared with the model group,giving drugs after aconite: Pinellia = 1:1 and aconite: Pinellia = 2:1 group,serum T levels increased,with significant difference(P < 0.05),Radix Aconiti Lateralis Preparata,Rhizoma Pinelliae 1:2 group had no obvious difference.The difference was not significant between the groups.Gastrointestinal hormone level changes: compared with health control group,model group,the serum gastrin and motilin levels appear to decrease,with significant difference(P < 0.05);compared with the model group,giving drugs after aconite: Pinellia = 1:1 and aconite: Pinellia = 2:1 group,the serum gastrin content increased,with significant difference(P < 0.05),aconite: Pinellia 1:2 groups had no significant difference,three to the medicine group,the serum motilin content were significantly increased(P < 0.05);the treatment group.There were no significant differences among The effects on rat heart,liver,kidney,spleen,small intestine Na~+_K--ATP activity: compared with the healthy control group,model group,heart kidney,spleen,intestinal Na~+ activity of_K--ATP decreased,there was significant difference(P<0.05),significant changes of hepatic Na~+_K--ATP enzyme activity was observed;compared with the model group after giving drugs,heart and blood of rat liver,kidney and spleen,intestinal Na~+_K--ATP enzyme activity were increased,there was significant difference(P<0.05)between the three groups;comparison: =1:1 group and Pinellia aconite aconite: compared with Pinellia group =1:2,rat heart,spleen,kidney and small intestine Na~+_K--ATP activity was significantly increased,there were significant differences(P<0.05),no change in Na~+_K--ATP enzyme activity in the liver significantly;and aconite: Pinellia ternata =2:1 group and =1:1 group: compared aconite and Pinellia,there were significant differences in the activity of_K--ATP Na~+(P<0.05),and there was no significant difference in_K--ATP Na~+ activity in liver,kidney,spleen and small intestine tissues.Conclusion1.On the medianlethal dose in mice.This study found that with the compatibility of aconite in proportion or decline of Pinellia ternata proportion rising.Half of the mice lethal dose increased,indicating that the compatibility of the toxic effect of the drug is mainly Banxia instead of aconite,also conversion of the LD50 of the mice for adult dose far outweigh drug clinical general dose,which in a certain extent that clinical medicine is relatively safe.In addition,the experimental results of the mice exposed to heart,liver,spleen,kidney,brain multiple tissue organ index were abnormal,signs of change also involves abnormal function of different systems of the body,indicating that the effect of monkshood tuber of Pinellia on the body is multiple organ and system,.2.Aconite tuber of Pinellia combination can significantly improve Yang deficiency model rats serum levels of cAMP / cGMP,improve the hypothalamus-pituitary-target added to thyroid,adrenal and gonadal axis hormone level,and improve the function of intestines and stomach Yang deficiency rats,and the rats heart,liver,kidney,spleen and small intestine tissue Na~+_K--ATP enzyme activity,and improve the level of energy metabolism.Each organ and tissue pathological Yang deficiency model rats liver,thymus,kidney,in addition to some changes,almost no change or change the other organs had not significant difference. |
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