| ObjectiveSummary the inheritance and development of the Wuhuanlin professor for chinese medicine master Deng Tietao’s five internal organs related theory in the treatment of coronary heart disease. Analysising the law of Wu huanlin professor’s clinical drug experience in five internal organs related theory treating coronary heart disease by the method of data mining.The core drug is determined by the mutual evidence of clinical medicine law mining results and academic theory. Explore the effect and the mechanism of the core drugs’anti platelet aggregation and Anti arterial thrombosis. Provide the basis for clinical medication experience.MethodsStudy of academic thoughtThe origin and development of five internal organs related theory in the treatment of coronary heart disease academic is combed through the literature search and following the clinic.Analysising the law of Wu huanlin professor’s clinical drug by data miningCollect the medical records of Professor Wu Huanlin according to the inclusion and exclusion criteria, and formate the available database specification through standarding and structuring data. The medication experience is analyzed through Traditional Chinese Medicine Inheritance Support Platform, using frequency statistic, four properties and five tastes statistics, drug tropism statistic, drug pattern analysis and rule analysis based on association rules, correlation degree analysis of drug based on improved mutual information method, drug combination extraction analysis based on complex system entropy clustering, new formula combination analysis based on non supervised entropy hierarchical clustering.Experimental study66 SPF SD rats were randomly divided into 6 groups:blank group, high dose group, middle dose group, low dose group and positive control group, each group of 12 rats, model group was 6, intervention for 7 days.The application method of ferric chloride is used for making the carotid artery thrombosis model in the model group, half of high dose group, half of middle dose group, half of low dose group, half of the positive control group. Half of the blank group were given sham operation. Analyze the effect of the experimental drug in the treatment of artery thrombosis by monitoring carotid artery blood flow and observing pathological section.The rest of the rats were managed by the detection of platelet aggregation rate by light turbidity method, the detection of platelet cyclic adenosine monophosphate (cAMP) by enzyme-linked immunosorbent assay, the detection of PI3K-Akt and PKC-Erk pathway protein by blot western to analyze the mechanism of anti platelet. ResultsFive internal organs related theory is derived from five elements theory. It generated on the limitations of the theory of the five elements and clinical practicing needing. Professor Wu huanlin has refined and developed five internal organs related theory in the treatment of coronary heart disease on the basis of the original. It is gradually becoming more mature. On the basis of inheritance and development, five internal organs related theory in the treatment of coronary heart disease can be divided into three stages:heart and liver related stages, heart and spleen related stages, lung and kidney related stage. There are different pathogenesis, different therapeutic methods and prescriptions in different stage.Reserch of medicine laws:1044 prescriptions were included in this study. The frequencies, four properties and five tastes, channel tropism of drug were analyzed.41 drug’s use frequency was more than 100 times. Analysis of the drug tropism statistic:the distribution frequency is from high to low in order: the spleen, lung, stomach, liver, heart, kidney, colon, bladder, gallbladder, pericardium, triple burner, small intestine. The four properties classification of drugs is from high to low:warm, cool, cold, hot. The five tasts of the medicine is from high to low:sweet, bitter, pungent, light, salty, sour, astringent. The number of support leve is set to 550, the confidence leve is set to 0.9, getting a total of 45 medication patterns, involving 7 drugs. The number of support leve is set to 500, involving 8 drugs. The number of support leve is set to 450, involving 9 drugs. The number of support leve is set to 550, the confidence leve is set to 0.9, getting a total of 101 dug rule. The number of the confidence leve is set to 0.98, getting a total of 38 dug rule. Drug composition extraction analysis based on complex system entropy clustering, the correlation degree was set to 8, the degree of punishment is set to 2, cluster analysis is carried out to get the correlation degree between drugs, there are 24 drugs with a correlation coefficient of more than 0.03. Complex system entropy clustering based drug extraction group, setting related degree and the degree of punishment, The 20 core combinations of 3-4 drugs were obtained. Unsupervised hierarchical clustering algorithm based on entropy,10 new combinations of potential new parties are obtained.There was no significant difference between the six groups in the carotid artery blood flow measurement before modeling (P>0.05). The carotid artery blood flow increased in high dose group comparing to model group at the 15min of modling (P<0.05). The carotid artery blood flow increased in middle dose group and high dose group comparing to model group at the 25min of modling (P<0.01). Paraffin sections and HE staining:experimental drugs reduce the amount of blood clots of carotid artery of model in a dose-dependent manner. Platelet aggregation rate of middle and high dose group comparing to model group were lower, the difference is statistically significant (P<0.05, P<0.01). Platelet cAMP of experimental drugs in high dose group comparing to model group was higher, the difference is statistically significant(P<0.01). Analysis of western blot:the high dose experimental drug group can reduce the expression of platelet PI3Kp110 (P<0.05). High dose group reduced the expression of p-Akt/t-Akt in platelets (P<0.01). Compared with the ADP group, the low, medium and high dose groups of the experimental drugs could not change the expression of p-pkc in the platelet (P>0.05). The high dose group of the experimental drugs could reduce the expression of p-erk/t-erk(P<0.05). Conclusionfive internal organs related theory is derived from five elements theory. It generated on the limitations of the theory of the five elements and clinical practicing needing. Professor Wu huanlin has refined and developed five internal organs related theory in the treatment of coronary heart disease on the basis of the original. It is gradually becoming more mature.Medication rule mining:under the premise of the heart and spleen related stages stage accounting for a large proportion, drugs mainly include the following types:supplementing qi and strengthening spleen, dissipating phlegm and dampness, promoting blood circulation to remove blood. The drug meridian tropism were mostly the spleen, stomach, lung, liver, heart and kidney. Four properties of the drugs were mostly the warm and mild. Five tastes of the drugs were mostly sweet, bitter, pungent. Demonstrate the main drug model, drug rules, associated drug pair, the combination of drug extraction, the potential of the new party, etc.Antiplatelet mechanism study:experimental drugs is useful on anti SD rat carotid artery thrombosis, increasing carotid artery blood flow of manufacturing mode, reducing the platelet aggregation rate. The mechanism may be to increase the expression level of cAMP, and inhibit the activation of PI3K-Akt-erk signaling pathway. |
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