| "Correlation between Formula and Syndrome" is an important logic proposition in diagnosis and treatment based on symptoms differentiation and formula -ology.The function and usage of formula not only have correlation with medical compatibility but also compatible with the syndrome which it will have effect on, that is the main effect of the formula depends on a considerable extent on the pathology and the role of targets of medical compatibility.The different syndrome should correspond to different treatment principals and formulas,"the treatment principals based on syndromes,different formulas based on syndromes".There is a problem of extent of correlation between the formula and syndrome.In recent years, many researchs mainly probed "Correlation between Formula and Syndrome" from static or space condition of syndromes,There are few research carrying out it from dynamic evolutionary of syndromes or the development of disease along with time.It is a good thought that probed "Correlation between Formula and Syndrome" from dynamic evolutionary of syndromes along with time based on the dynamic evolutionary character of syndromes.The research takes"Correlation between Formula and Syndrome'as logic basis, is mainly based on the theory of etiology and pathology of Type 2 Diabetes Insulin Resistance in western medicine and features of etiology and pathology and treatment in Chinese medicine.During replicated the rats model of Type 2 Diabetes Insulin Resistance,by observing appearance and behavior of the rats model and analysing multiple indicators of experiment in biological system concomitantly corresponding TCM's syndromes,we explored the dynamic evolutionary progression of syndromes and pathology;On this basis,we selected some formulas which correlated with TCM's syndromes on some extent and influenced on the rats model in different phases.Compared the biological effects of different formulas by the research methods of correlation and exclusion,that is different formulas for one syndrome.To explore the relationship between the function and usage of formula and TCM's syndromes,and we also discussed the biological foundation of different formulas.Finally,we explored genes expression about PPAR-r mRNA and InsR mRNA in fattiness of the model and the effection of the best chinese medicine influencing the rats model by applying with Real Time quantitative PCR technology,and approached molecular mechanism of chinese medicines influencing the model.The thesis is divided into two main parts:literature review and experimental research.Literature review is mainly focused on three aspects:The relationship between Formula and Syndrome in TCM;Review of the study about Insulin Resistance of Type 2 Diabetes in morden medicine and the study about experimental model of Type 2 Diabetes IR;Review of the study about Insulin Resistance of Type 2 Diabetes in traditional chinese medicine.Experiment study is mainly focused on three aspects:the study about the dynamic evolutionary progression of syndromes and pathology on the rats model of Type 2 Diabetes Insulin Resistance;Comparsion the biological effects of different formulas correlated TCM's syndromes pathology in different phase based on the progressive syndrome on the rats model of Type 2 Diabetes Insulin Resistance;the study of mechanism of the effective chinese medicine influence on the model.Research 1:The study about the dynamic evolutionary progressive of syndromes and pathology on the rats model of Type 2 Diabetes Insulin ResistanceMethods:The research set on the rats model by feeding with high glucose and fat diet together with peritoneal injection of STZ.SD rats were randomly divided into the control group(50 rats) and model group(60 rats).During 1-5w,the control group were fed with normal food,the model group were fed with high glucose and high calories food.In the 6th week,the model group were injected with STZ (30mg/kg) at abdomino.We selected model rats which measure up the standard (FPG≥11.1mmol/L,Fins 20-40uIU/ml)into the experiment.At the end of 0,6,8, 10,12 week,the rats were killed and taken blood and tissure.We used biological and chemical method to measure FPG,TC,TG,HDL-c,LDL-c,serumand plasma were measured by radioimmunoassay(RIA) to test the contents of Fins, TNF-α,Leptin,IL-6,cAMP,cGMP.Using DWN-90 blood liqid analyse apparatus to measure the whole blood viscosity at 200/s,5/s shear rate and plasma viscosity.Results:1) Appearance and behavior:During 6w-8w,the model rats appear lethargy, narrow their eyes,accidie,still,loss of hair,drinking increase,dejecta desiccation,sweatiness and wateriness at tail.During 9w-10w,the model rats appear fatness,extrados,gather together,narrow their eyes,accidie,action slow,fatness in hair which based on syndromes at first phase;During 11w-12w,the model rats appear continually loss of hair and turn into yellow color at stern,some petechias appear at the tail from top to root.Compared with the control group,the weight of the model group rises up obviously at 4th week,and lowers continually from 9th week,higher obviously than the control group.2)Glucose metabolism:Compared with the control group,the FPG,Fins,IRI level of the model group were increased continually from the end of 6th week,reached its top at the end of 12th week.the IAI level were decreased obviously from the end of 6th week,reached its bottom at the end of 12th week.3)Lipid metabolism:Compared with the control group,The TC,LDL-C level of the model group were increased continually from the end of 8th week,reached its top at the end of 12th week.The TG level were increased obviously from the end of 10th week,reached its top at the end of 12th week.The HDL-C level of the model group were decreased during 0-6w,were increased during 6-8w,were decreased obviously at the end of 10th week,reach its bottom at the end of 12th week.4)Adipokines:Compared with the control group,the TNF-a,Leptin,IL-6, cAMP,cAMP/cGMP level of the model group were increased continually from the end of 6th week,reached their top at the end of 12th week.The cGMP level of the model group were decreased from the end of 6th week,reached its bottom at the end of 12th week.6)Haematological change:The whole blood viscosity and plasma viscosity of the control group have no change.Compared with the control group,the whole blood viscosity and plasma viscosity of the model group at 200/s,5/s shear rate were increased continually from the end of 10th week,reached it top at the end of 12th week.Conclusions:The rats model of T2DM IR which feeding high glucose and fat diet together with peritoneal injection of STZ appeared characters of dynamic evolutionary syndroms and corresponding biological items change during different phases.The model manifested hyperglycemia,hyper-insulinemia,high level cholesterin and triglyceride after IR.The dynamic evolutionary progression of syndromes and pathology in different phases are simultaneous deficiency of both qi and yin→simultaneous deficiency of both qi and yin concurrent phlegm turbidness→simultaneous deficiency of both qi and yin concurrent phlegm turbidness and blood stasis.Research 2:Comparison of biological effects of different formulas correlated syndrome based on the progressive syndrome on the rats model of Type 2 Diabetes Insulin ResistanceMethods:The research set on the rats model by feeding with high glucose and fat diet together with peritoneal injection of STZ.SD rats were randomly divided into the control group(30 rats) and model group(170 rats).During 1-Sw,the control group were fed with normal food,the model group were fed with high glucose and high calories food.In the 6th week,the model group were injected with STZ(30mg/kg) at abdomino.We selected model rats which measure up the standard into the experiment.The rats were randomly divided into the model group 1,the model group 2,the model group 3,the xiyao group 1,the xiyao group 2,the xiyao group 3, 10 rats each group.the first phase intervention of chinese medicine 30 rats,the second phase intervention of chinese medicine 30 rats,the third phase intervention of Chinese Medicine 30 rats,The rats of the control group were divided into the control group 1,the control group 2,the control group 3.the control groups were fed with normal food continually,other groups were fed with high glucose and high calories food.First phase:From the 7th week,the control group 1 and the model group 1 were administrated the distilled water,the xiyao group 1 were administrated Pioglitazone(1.35mg/kg/d),The rats of first phase intervention of chinese medicine were divided into A formula group,B formula group,C formula group,they were administrated respectively with A formula(5.31g/kg/d),B formula(3.15g/kg/d),C formula(3.15g/kg/d) for two weeks.Second phase:From the 9th week,the control group 2 and the model group 2 were administrated the distilled water,the xiyao group 2 were administrated Pioglitazone(1.35mg/kg/d),The rats of second phase intervention of chinese medicine were divided into A+B formula group,A formula group,B formula group,they were administrated respectively with A+B formula(8.46g/kg/d),A formula(5.31g/kg/d),B formula(3.15g/kg/d) for two weeks.Third phase:From the 11th week,the control group 3 and the model group 3 were administrated the distilled water,the xiyao group 3 were administrated Pioglitazone(1.35mg/kg/d),the rats of third phase intervention of chinese medicine were divided into A+B+C formula group,A+B formula group,B+C formula group, they were administrated respectively with A+B+C formula(11.61g/kg/d),A+B formula(8.46g/kg/d),B+C formula(6.30g/kg/d )for two weeks.The rats were killed and taken blood and tissure to measure at different phases.Results:First phase:Compared with the control group,the FPG,Fins,IRI level of the model group were increased obviously,the IAI level were decreased obviously,the FFA,Leptin,TNF-a,IL-6,cAMP,cAMP/cGMP level were increased obviously,the ET level were increased obviously.Compared with the model group,the FPG,Fins,IRI,IAI,and TG,TC,HDL-c,LDL-c level of A formula group,B formula group and C formula group have no change.The Leptin,TNF-αand cAMP,cAMP/cGMP level of the A formula group was decreased obviously,B formula group and C formula group have no change on these.A formula group,B formula group and C formula group have no effect on the whole blood viscosity at the 200/s,5/s shear rate and plasma viscosity of the model group.A formula group,B formula group have no effect on the ET-1 of the model group.The ET-1 level of the C formula group was decreased significantly.The A formula group,B formula group and C formula group have no effect on Pancreas pathomorpholgoy.Second phase:Compared with the control group,the FPG,Fins,IRI level of the model group were increased obviously,the IAI level were decreased obviously,the TC,LDL-c level were increased obviously,the FFA,Leptin,TNF-a,IL-6,cAMP, cAMP/cGMP level were increased obviously,the ET level were increased obviously. Compared with the model group,the FPG,Fins,IRI level of the A+B formula group were decreased obviously,the IAI level were increased obviously.The TC,LDL-C level of the A+B formula group were decreased.The FFA,Leptin,TNF-α,cAMP,cAMP/cGMP were decreased.The ET level were also decreased.The Fins level of the A formula group was decreased,the Leptin,TNF-α,cAMP,cAMP/cGMP level of the A formula group was decreased.The Fins level of the B formula group was decreased,the TC,FFA level of the B formula group was decreased obviously.The A+B formula group,A formula group and B formula group have no effect on Pancreas pathomorpholgoy.Third phase:Compared with the control group,the FPG,Fins,IRI level of the model group were increased significantly,the IAI level were decreased significantly,the TC,TG,LDL-c level were increased obviously,the HDL-c level was decreased obviously,the FFA,Leptin,TNF-a,IL-6,cAMP,cAMP/cGMP level were increased obviously,the level of the whole blood viscosity at the 200/s,5/s shear rate and plasma viscosity were increased obviously,the ET level were increased obviously.Compared with the model group,the FPG,Fins,IRI level of the A+B+C formula group were decreased obviously,the IAI level was increased obviously.The TC,LDL-C level of the A+B+C formula group were decreased.The FFA,Leptin, TNF-α,IL-6,cAMP,cAMP/cGMP level were decreased obviously.The level of the whole blood viscosity at the 200/s,5/s shear rate and plasma viscosity of A+B+C formula group were decreased.The ET level of A+B+C formula group was decreased obviously.The FPG,Fins,IRI level of the A+B formula group were decreased,the IAI level was increased.The TC,LDL-C level of the A+B formula group were decreased.The FFA,Leptin,TNF-α,cAMP,cAMP/cGMP level of the A+B formula group were decreased.The ET level of A+B formula group was decreased.The Fins,FFA level of the B+C formula group were decreased,The level of the whole blood viscosity at the 200/s,5/s shear rate and plasma viscosity of B+C formula group were decreased.The ET level of the B+C formula group was decreased obviously.The A+B+C formula group have good effect on some extent to Pancreas pathomorpholgoy.Conclusions:In different phases,the different formulas which representated different treatment principals have many effects on some extent to corresponding TCM's syndromes/disease.In the first phase,compared the whole effection of A formula,B formula,C formula,we found that the intervention of A formula are better than B formula and C formula,and we concluded A formula have the close correlation with syndromes in this phase.In the second phase,compared the whole effection of A+B formula,A formula,B formula,we found that the intervention of A+B formula were the best in three groups,the next was A formula,the intervention of B formula were not good.we concluded A+B formula have the close correlation with syndromes in this phase.In the third phase,compared the whole effection of A+B+C formula,A+B formula,B+C formula,we found that the intervention of A+B+C formula are the best in three groups,we concluded A+B+C formula have the close correlation with syndromes in this phase.Research 3:the mechanism study of the effective chinese medicine influence on the rats model of Type 2 Diabetes Insulin ResistanceMethods:According to results of the former study,we selected the best effective formula—A+B+C formula,which has the closest correlation with disease and syndrome,we took it as the chinese medicine intervention group,and measured the expression of PPAR-γmRNA and InsR mRNA in fat by using the Real-time quantitative PCR.To explore mechanism of A+B+C formula influenceing on the rats model of Type 2 Diabetes Insulin Resistance.Results:The effects on the expression of PPAR-γmRNA and InsR mRNA in fat of A+B+C formula:Compared with the control group,the expression of PPAR-γmRNA and InsR mRNA in fat of the model group were significantly decreased(P＜0.05).Compared with the model group,the expression of PPAR-γmRNA in fat of the xiyao group and A+B+C formula group were significantly increased(P＜0.01),the expression of InsR mRNA in fat were increased on some extent,but there was no distinct difference(P=0.060或P=0.061).Compared with the xiyao group,the expression of PPAR-γmRNA in fat of A+B+C formula were significantly decreased(P＜0.05).Conclusions:We concluded that treatment mechanism of A+B+C formula (yiqiyangyin huatanhuoxue fang)to treat Type 2 Diabetes may act as a similar way of Thiazolidinediones(TZD),involving to activate PPAR-γand increased InsR. To sum up,the findings indicated that the yiqiyangyin huatanhuoxue fang have effect on decreasing FPG,Fins level,enhancing the sensitivity of skeletal muscle and liver to insulin,ameliorating IR,correcting lipid metabolism turbulence,slowing the release of FFA,Leptin,TNF-a,IL-6,ameliorating haematological abnormity,the whole effection are same as Pioglitazone.the chinese medicine have other superority in treatment,for exemple,protecting endothelium cell of blood vessel,accommodating lipid metabolism,preventing blood coagulation,this showed the character that interventiong many aspect of chinese medicine compounds.Innovation and Meaning:1)the research found that the rats model of T2DM IR which feeding high glucose and fat diet together with peritoneal injection of STZ appeared characters of dynamic evolutionary syndroms and corresponding biological items change during different phases.It offers a worth model for the study of"Correlation between Formula and Syndrome"from dynamic evolutionary progressive of disease and syndrome.2)Comparison of biological effects of different formulas correlated syndrome based on the progressive syndrome on the rats model of Type 2 Diabetes Insulin Resistance with the research methods of correlation and exclusion and different formulas for one syndrome.The research found the different formulas have different function characteristics,they have have correlation on some extent to corresponding TCM's syndromes/disease.3)It demonstrated the rationality about making out treatment methods based on different syndromes.The study of mechanism found that treatment mechanism of A+B+C formula to treat Type 2 Diabetes may act as a similar way with Thiazolidinediones(TZD).they are both activating PPAR-γ,enhancing the sensitivity of skeletal muscle and liver to insulin, accommodating some adipokines level,improving glucose and liquid metabolism ameliorating IR.The research not only carried out beneficial technology exploration for revealing the important logic proposition of"Correlation between Formula and Syndrome",but also provided objective evidence for recognizing "Correlation between Formula and Syndrome"and its scientific connotation. |
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