| ObjectiveThe study preliminarily seeked for the constitution features of Intractable Epilepsy and observed how Chai bei zhi xian decoction control the effect mechanism of P-gp through inflammatory pathways, in order to lay the foundation for the new thinking of better treatment mechanism research and search for the treatment based on constitution of Intractable Epilepsy.MethodsResearch one The investigation of the constitution features of Intractable EpilepsyThe general clinical information in patients with Intractable Epilepsy was gathered by filling in the clinical observation table, classification and determination of TCM constitution scale, Athens insomnia scale(AIS), Epworth Sleepiness Scale(ESS), Hamilton Anxiety Scale(HAMA) and Hamilton Depression Scale(HAMD), Quality of life in epilepsy inventory-89(QOLIE-89), etc. The distribution characteristic of every type of TCM constitution for patients with IE was analyzed. Gender, age, severity, body mass index and other differences in nine constitutions of IE patients were compared by using chi-square, and so was the analysis of comorbidities in IE patients with different constitution, such as anxiety, depression, insomnia, drowsiness; The constitution differences between IE and non-IE were compared by using the nonparametric test; The relationship between constitution and life quality of patients with IE was investigated by using bivariate correlation analysis and multivariate stepwise regression.Research two Mechanism research on Chai bei zhi xian decoction controlling P-gp through inflammatory pathways in RBMECIt was an in vitro experiment by making Rat Brain Microvascular Endothelial Cells (RBMEC) exposed to TNF alpha, screening of TNF alpha concentration, and induces higher expression of P glycoprotein, to prepare cell model. Then model cells were treated with different concentrations of drug-containing serum of Chai bei zhi xian decoction rats and serum of normal rats. Western blot experiments, RT-PCR were used to test the protein and mRNA expressions of PKCa, eNOS, P-gp. Statistics was used to compare the differences between groups.ResultsResearch one The investigation of the constitution features of Intractable Epilepsy1. Basic information:compared with non-IE, IE patients’onset age were more in the age less than 12 (P< 0.01). And the number of patients who got idiopathic epilepsy (P< 0.05), had the heavier severity (P< 0.01), took two kinds of drugs (P< 0.01), got moderate abnormal in electroencephalogram (EEG)(P< 0.01) and were overweight (P< 0.01),were more likely in patients with IE than that with non-IE.2. The distribution characteristics of TCM constitution(1) The overall situation:19 cases of total 100 patients with IE were of gentleness type (19%) and others were of biased constitution (81%). The occurrence rate of biased constitution type decreased in wet-heat (40%), Qi-deficiency (38%), Qi-depression (34%), Yang-deficiency (27%), phlegm-wetness (25%), Yin-deficiency (23%), blood stasis (9%) and special diathesis (6%).Among them, the number of Yang-deficiency deficiency (P< 0.05), Qi-deficiency (P< 0.01), phlegm-wetness (P< 0.01), wet-heat (P< 0.01) and Qi-depression (P< 0.01) were more in the patients with IE than that with non-IE. And the number of gentleness type was more in patients with non-IE than that with IE (P< 0.01).(2) The gender distribution characteristics of constitution:women were more than men in Qi-deficiency (P< 0.01).(3) The age distribution characteristics of constitution:the proportion of gentleness type was higher than others in the stage of lesser than 18 years old (P< 0.01). The proportion of phlegm-wetness is higher than others in the stage of equal or greater than 40 years old (P< 0.01). The proportion of blood stasis was higher than others in the stage of of 18 to 40 years old (P< 0.05).(4) The different severity distribution characteristics of constitution:the distribution structure of nine constitution types has no obvious difference (P>0.05).(5) The BMI distribution characteristics of constitution:the distribution structure of nine constitution types has no obvious difference (P>0.05).3. The occurrence of comorbid illnesses with intractable epilepsy in different constitutional types(1) Anxiety:the distribution structure of nine constitution types has no obvious difference (P>0.05)(2) Depression:the proportion of Yang-deficiency (P<0.01) and Qi-depression (P<0.05) was larger in depression patients than in non-depression patients; Compared with non-IE, IE patients got higher depression score (P<0.05) and the proportion of Yang-deficiency deficiency (p< 0.05), wet-heat (p< 0.05) and Qi-depression (P<0.05) was larger.(3) Insomnia:the proportion of Yang-deficiency (P<0.01) and Qi-depression (P<0.01) was larger in IE patients; Compared with non-IE, IE patients got higher insomnia score (P<0.05), and the proportion of wet-heat (P< 0.05) and Qi-depression (P< 0.01) was larger.(4) EDS:the proportion of phlegm-wetness (P<.05) and wet-heat (P<0.05) was larger in IE patients; Compared with non-IE, the proportion of phlegm-wetness (P< 0.05) and wet-heat (P< 0.05) was larger in IE patients.4. The correlation between constitution and quality of life(1) The results of bivariate correlation analysis:there was a positive correlation between the quality of life scores and gentleness constitution score. In biased constitution, Yin-deficiency and memory were positively correlated. Qi-deficiency and Role limitations-emotional, pain and total score were negatively correlated; Phlegm-wetness and total score were negatively correlated. Wet-heat and health perceptions and medication effects were negatively correlated. Special diathesis and health perceptions, overall quality of life, role limitations-physical, role limitations-emotional, pain, working/driving/social function, emotional wellbeing, language, medication effects, social isolation and total score were negatively correlated. Qi-depression and health perceptions, role limitations-emotional, language, medication effects, social support and total score were negatively correlated.The differences above were statistically significant (P<0.05).(2) The results of multiple stepwise regression analysis:Qi-depression mainly affected the health perceptions (P<0.01), medication effects (P<0.01) and total score (P<0.01). Special diathesis mainly affected role limitations-emotional (P<0.01) and pain (P<0.01).Research two Mechanism research on Chai bei zhi xian decoction controlling P-gp through inflammatory pathways in RBMEC(1) The influence of drug-containing serum of Chai bei zhi xian decoction rats on the expression of P glycoprotein, PKC a, eNOS on RBMEC:RBMEC were exposed to TNF alpha with the concentration of 20 ng/ml, in order to prepare cell model with high expression of P glycoprotein. After being treated with drug-containing serum of Chai bei zhi xian decoction rats and serum of normal rats, the expression of P glycoprotein was observed to be lower in drug-containing serum groups 10% and 20% and the normal groups than in the model groups(P<0.01). The expression of PKC a was observed to be lower in all other groups than in the model groups. The expression of eNOS was observed to be lower in all other groups than in the model groups. The differences were statistically significant (P<0.05).(2) The influence of drug-containing serum of Chai bei zhi xian decoction rats on the expression of P glycoprotein mRNA, PKC a mRNA, and eNOS mRNA on RBMEC:The expression of P-gp mRNA, PKC a mRNA and eNOS mRNA was increased in model groups, compared with the normal groups. And the expression was reduced in all the serum groups compared with the model groups (P<0.05).Conclusions1. The biased constitution is the priority type in IE patients. The highest occurrence rate of biased constitution type decreased in wet-heat, Qi-deficiency and Qi-depression. The proportion of gentleness type was higher in non-IE.2. The distribution of constitution in IE patients was different in gender and age. Women were more than men in Qi-deficiency. Gentleness type was higher than others in the stage of lesser than 18 years old.The proportion of phlegm-wetness is higher than others in the stage of equal or greater than 40 years old. The proportion of blood stasis was higher than others in the stage of of 18 to 40 years old.3. The proportion of Yang-deficiency and Qi-depression was larger in depression patients than in non-depression patients. Compared with non-IE, IE patients got higher depression score and the proportion of Yang-deficiency deficiency, wet-heat and Qi-depression was larger. The proportion of Yang-deficiency and Qi-depression was larger in IE patients with insomnia. Compared with non-IE, IE patients got higher insomnia score, and the proportion of wet-heat and Qi-depression was larger. The proportion of phlegm-wetness and wet-heat was larger in IE patients with EDS. Compared with non-IE, the proportion of phlegm-wetness and wet-heatwas was larger in IE patients.4. The quality of life in IE patients was associated with constitution. Gentleness type played a promote role in every item of the quality of life. Qi-depression and special diathesis had great influence on quality of life.5. Chai bei zhi xian decoction reduced the expression of P-gp by lowering the expression of PKC a and eNOS, in order to cut down pumping function of P-gp and increase drug sensitivity.6. This research followed the thought "preventing disease before its occurrence and preventing disease from exacerbating" in traditional Chinese medicine. It provided a certain basis for further treatment based on constitution and a new thinking of treatment of intractable epilepsy by constitutional differentiation and treatment in traditional Chinese medicine. At the same time, Chai bei zhi xian decoction could control P-gp through inflammatory pathways, which provided a new basis for TCM therapeutic mechanism of intractable epilepsy. And it was possible for increasing the sensitivity of the antiepileptic drugs by syndrome differentiation and treatment for intractable epilepsy. The two research above laid a foundation of combination of syndrome and constitution and made it possible to improve the curative effect of refractory epilepsy in the future.
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