| Objective To establish lung cancer rat model with Yin deficiency and heat syndrome under combination theory of TCM syndrome and to evaluate the rat model.To observe changes of traditional Chinese Medicine macroscopic indexes and Laboratory microscopic indexes caused by herb pair of Artemisia annua and Turtle in model rats and to study the pharmacokinetic characteristics of drug,pair of Artemisia annua and Turtle which were described by successful establishing model.To analysis the law of action about herb pair of Artemisia annua and Turtle and to prived a certain experimental basis for clinical medication.Methods The establishment and evaluation of lung cancer rat model of yin deficiency heat syndrome:Making the rats form Yin-deficiency constitution by some factors including smoking,filling the rats stomach with thyroid hormone tablets and warm traditional Chinese Medicine,and than injecting Walker-256 cells through tail vein in rats to build model.At last,the model was evaluated by observing changes of traditional Chinese Medicine macroscopic indexes and Laboratory microscopic indexes.Study on Compatibility Regularity of Drug Pair of P Artemisia annua and Turtle in Pharmacodynamics:Rat models were randomly divided into groups including blank group,model group,turtle group,Artemisia annua group,drug group and positive drug group and given the extract.Observing and analyzing the traditional Chinese Medicine macroscopic indexes during the medication,stopping medication until death,continue to observe the corresponding indicators to finish pharmacodynamic evaluation.Study on pharmacokinetics of herb pair of Artemisia annua and Turtle in model rats:Selecting the antipyretic active ingredients including scopoletin,artemisinin,arteannuin B as index components.LC/MS was used for examining,the pharmacokinetic parameters were calculated by PKSolver software.Results The establishment and evaluation of lung cancer rat model of yin deficiency heat syndrome:Model rats had yellow fur with shedding,eating les,increasing water intake,moving bowels dry,lightly red and dark tongue;serum CEA content was increased,the levels of TNF-α and IL-1β increased significantly,serum T3and T4 contents were also increased.It was found that there were obvious tumor characteristics in lung through Anatomical observation and pathological observation and no metastasis of other organs.Study on Compatibility Regularity of Drug Pair of P Artemisia annua and Turtle in Pharmacodynamics:After administration,the efficacy of the herb pair was verified on both traditional Chinese Medicine macroscopic indexes and Laboratory microscopic indexes,especially in syndrome of extreme heat due to deficieny of yin,such as reducing water intake,increasing stool water content,improving the tongue image.In addition,the levels of nternal heat source including IL-1 and TNF-α could be reduced by the herb pair and there were significant differences among different groups(P<0.01,P<0.05).Comparing with other groups the herb pair group was the only one which the content of IL-1 was decreased.The ratio of serum cAMP/cGMP in the herb pair group tended to be normal.The content of serum cAMP in herb pair group was lower than model group,and there was significant difference between two groups(P<0.05).The content of serum cGMP in herb pair group was higher than model group,and there was no significant difference between two groups(P>0.05).Compared with the model group,the content of serum T3 in the herb pair group was much lower,and there was significant difference between two groups(P<0.05),the content of Serum T4 had a tendency to decrease.The content of serum T3 in other groups also had a tendency to decrease which were compared with the model group.Study on pharmacokinetics of herb pair of Artemisia annua and Turtle in model rats:Using a gradient mobile phase:0.1%formic acid-water(A)and acetonitrile(B)(0-7min-12min,A:82%-40%-20%;B:18%-60%-80%).Using ionization source(ESI),Positive ion detection,determinating scopoletin and artemisinin blood concentration.Sample sizes of 0.0410-7.872、0.0354-6.7968ng showed a good linear relationship,the method had good specificity,high accuracy and good precision,and has no matrix effect.Conclusion In this study,a rat model of lung cancer with Yin deficiency and heat syndrome was established successfully.An idea was provided to establish models which were combining disease and syndrome for Traditional Chinese Medicine basic research.Foundation is established for further research into cancer fever.In this experiment,a rat model of lung cancer with Yin deficiency and heat syndrome was used to study the efficacy of herb pair for nourishing yin and diathermy.Its mechanisms were investigated,may as follows,the levels of nternal heat source including IL-1 and TNF-α could be reduced by the herb pair to make the body temperature regulation center play a normal role in body temperature regulation;the ratio of serum cAMP/cGMP tended to be normal and its mmune function can be influenced;the overactive state of Adenohypophysis-Thyroid Axis function was calmed down and serum T3and T4 contents were decreased.The method for determination concentration of scopoletin,arteannuin B,artemisinin concentration in blood samples was set up.The method for determination concentration of scopoletin and artemisinin concentration in blood samples was set up.Experimental basis for explaining compatibility law were provided by studying on pharmacokinetics of herb pair of Artemisia annua and Turtle in model rats and it was meaningful to guide clinical to use rational drugs. |