The Experimental Study Of Qibai Pingfei Capsule In The Prevention And Treatment Of Chronic Obstructive Pulmonary Disease Phlegm And Blood Stasis Syndrome

1 ObjectiveBased on the theory of traditional Chinese medicine "lung governing management and regulation,all vessels converging in lung"guidance, through the study of the relationship between chronic obstructive pulmonary disease "lung qi deficiency failure rule section and pulmonary vasoconstriction, the analysis and summary of chronic obstructive pulmonary disease with phlegm and blood stasis syndrome pathogenesis in traditional Chinese medicine. Through the animal experimental model was established in rats with chronic obstructive pulmonary disease with phlegm and blood stasis syndrome, and the application rule section reconstruction of Chinese medicine Qibaipingfei capsule intervention, to observe the COPD phlegm and blood stasis syndrome rats after experimental K-ATP correlation channel protein in lung function, hemodynamics, pulmonary artery and tissue such as NF-kB and ETA receptor and ETB receptor mRNA levels and pulmonary vasoconstriction relationship from the angle of animal experiment system. Through Qibaipingfei capsule effective interventions to achieve rule section reconstruction, regulation of K-ATP channels, inhibited pulmonary vasoconstriction, reduce pulmonary artery pressure, so as to explore the effect approach and target Qibaipingfei capsule intervention COPD pulmonary vasoconstriction.2 methods2.1 theoretical studysystem collect related literature of COPD phlegm and blood stasis syndrome, research status of screening and summary of chronic obstructive pulmonary disease with phlegm and blood stasis syndrome pathogenesis at home and abroad, evaluation and analysis of K-ATP channel inhibition pathway activated pulmonary vasoconstriction, a preliminary discussion on the effect approach and target compound Chinese medicine intervention in chronic obstructive pulmonary disease pulmonary vascular remodeling, to the study of Chinese medicine on chronic obstructive pulmonary disease truncation and reversal mechanism, so as to enrich the Chinese traditional medicine for the treatment of chronic obstructive pulmonary disease study content. 2.2 experimental studyThe rats were randomly divided into normal group (60 rats), model group (60 rats) and Qibaipingfei capsule in prevention group (40 rats) and Qibaipingfei capsule treatment group (40 rats) and nicorandil prevention group (40 rats), nicorandil therapy group (40 rats). Animal model with reference to Li Zegeng, Xiao Shiliang modeling method to establish the COPD phlegm and blood stasis syndrome. From the first day began to experiment in to establish COPD phlegm and blood stasis syndrome lung model except normal group rats, after the modeling gavage rats day by day. Model group and normal group daily physiological saline 10ml/kg, to four and eight weeks, twelve weeks materials twenty. drug intervention Prevention group In the mold, gavage after 4 weeks materials 20 rats,20 left gastric perfusion of normal feeding stop again after 4 weeks (i.e., experiment eighth weekend), the treatment group for drug intervention after the success of modeling, after 4 weeks (i.e., experiment eighth weekend) materials 20 rats,20 left gastric perfusion of normal feeding stop again after 4 weeks (i.e., experiment twelfth weekend). The drug dose: Nicorandil 10ml/kg (each ml containing nicorandil 0.3mg), Qibaipingfei capsule liquid 10ml/kg (each ml containing Qibai Pingfei capsule 50mg). With Yiqi Huatan Quyu method to observe the chronic obstructive pulmonary disease with phlegm and blood stasis syndrome rats with pulmonary function, hemodynamics and serum cytokine changes of lung tissue and nuclear transcription factor -KB protein content changes of pulmonary artery and the changes in lung tissue of ETA receptor and ETB receptor mRNA transcription changes in the level of. All the data were analyzed by SPSS17.0 software.3 Results3.1 The theoretical study resultslung governing management and regulation connotation is to regulate qi, blood, the water running, stable and coordinate their own internal environment and the effect of the balance, is a great summary of main physiological function of lung. Pulmonary failure rule section is the leading mechanism of chronic obstructive pulmonary disease; mechanism of lung governing management section reconstruction may be anti-inflammatory and slow down the airway remodeling process, through a variety of ways intervention Pulmonary vasoconstriction and remodeling, protecting vascular endothelial cell and effect of Pulmonary vasomotor function, so as to improve the function of right heart and Pulmonary function to reduce Pulmonary artery pressure and Pulmonary vascular resistance effect. This paper through theoretical research the basic pathogenesis of clear chronic obstructive Pulmonary disease is the rule section arrhythmia, Qi deficiency and phlegm, three reciprocal causation. In the stage of Pulmonary hypertension induced by chronic obstructive Pulmonary disease phlegm and blood stasis syndrome, "the atypical manifestation of Pulmonary failure rule section", and then put forward the rule section reconstruction method -yiqi huatan quyu therapy.3.2 the experimental study results3.2.1 Changes of lung function and hemodynamics in rats and the impact of Qibaipingfei Capsule3.2.1.1 Pulmonary function:In the prevention aspect:compared with the normal group, model group rats lung function FEV0.3, FVC, FEV0.3/FVC decreased (P< 0.01); compared with the model group, qiyu group, niyu group FEV0.3, FVC, FEV0.3/FVC, were significantly increased (P< 0.01); compared with the qiyu group, molding and drug four weeks, niyu group FEV0.3, FVC had significant difference (P< 0.01 or P< 0.05), and no difference in FEV0.3/FVC (P> 0.05); Withdrawal around four weeks, niyu group FEV0.3, FVC had significant difference (P< 0.01 or P<0.05), and no difference in FEV0.3/FVC (P> 0.05).From the aspect of treatment:compared with the normal group, model group rats lung function FEV0.3, FVC, FEV0.3/FVC decreased (P< 0.01); compared with the model group, qizhi and qiyu group FEV0.3, FVC, FEV0.3/FVC were significantly increased (P < 0.01); compared with the qizhi group, drug four weeks nizhi group only FEV0.3 and FVC had significant difference (P< 0.01 or P< 0.05), and no difference in FEV0.3/FVC (P> 0.05); Withdrawal around four weeks, only FEV0.3 and FVC group had significant difference (P< 0.01 or P< 0.05), and no difference in FEV0.3/FVC (P > 0.05).3.2.1.2 Hemodynamic detection:In the prevention aspect:compared with the normal group, model group mean pulmonary arterial pressure (mPAP) and the mean carotid arterial pressure (mCAP) increased significantly (P<0.01); compared with the model group, qiyu group,niyu group mPAP and mCAP were significantly decreased (P< 0.01); compared with the Qiyu group, molding and drug four weeks, niyu group mPAP and mCAP has no significant difference (P> 0.05); Withdrawal around four weeks, niyu group mPAP has no significant difference (P> 0.05), mCAP(P< 0.05) difference.From the aspect of treatment:compared with the normal group, model group mPAP and mCAP increased significantly (P< 0.01); compared with the model group, only qizhi group mPAP and mCAP were significantly decreased (P< 0.01); drug four weeks,only nizhi group mPAP and mCAP with the difference statistical significance (P<0.01); Withdrawal around four weeks, nizhi group mPAP showed no statistical significance (P> 0.05), there was significant difference of mCAP (P<0.01).3.2.2Changes of serum cytokine in rats and the impact of Qibaipingfei Capsule3.2.2.1 Determination of the content results of ET-1 and HIF-1 in rats serumIn the prevention aspect:compared with the normal group, model group ET-1 and HIF-1 alpha content increased significantly (P< 0.01); compared with the model group, qiyu group, niyu group ET-1 and HIF-1 were all decreased (P<0.01 or P<0.05); compared with the qiyu group, drug four weeks, niyu group ET-1 and HIF-1 had difference significance (P< 0.05); Withdrawal around four weeks, qiyu group and niyu groupET-land HIF-1 had statistical difference significan cedifferences (P< 0.01).From the aspect of treatment:compared with the normal group, model group ET-1 and HIF-1 alpha content increased significantly (P< 0.01); compared with the model group, drug four weeks,qizhi group,and nizhi group ET-1, HIF-1 were all decreased, the difference was statistically significant(P< 0.01 or P< 0.05), Withdrawal around four weeks, qiyu group and niyu group ET-1, HIF-1 content was significantly decreased, the difference was statistically significant (P<0.01), no statistically significant differences with nizhi group (P> 0.05); and compared with the qizhi group,Withdrawal around four weeksqiyu group and niyu group ET-1, HIF-1 alpha had no significant difference (P> 0.05); Withdrawal around four weeks nizhi group ET-1 had no statistical difference (P> 0.05), only HIF-1 alpha was significant difference with nizhi group (P< 0.01).3.2.2.2 Determination of the content results of CAM-2 and VEGF in rats serumIn the prevention aspect:compared with the normal group, model group CAM-2 content was significantly decreased, VEGF content increased significantly, the difference was statistically significant (P< 0.01); compared with the model group, qiyu group,niyu group, CAM-2 content increased, VEGF content decreased significantly, the difference was statistically significant (P< 0.01); compared with the qiyu group, CAM-2 molding and drug four weeks there was statistical significance difference (P< 0.05), VEGF showed no statistically significant difference (P> 0.05); Withdrawal around four weeks qiyu groups in CAM-2, VEGF difference(P< 0.01 or P< 0.05).From the aspect of treatment:compared with the normal group, model group CAM-2 content was significantly decreased, VEGF content increased significantly (P< 0.01); compared with the model group, molding and drug four weeks qiyu group and niyu group, CAM-2 were increased, VEGF content decreased significantly, there was significant difference(P< 0.01); Withdrawal around four weeks CAM-2 were increased, VEGF content decreased, the difference was statistically significant (P< 0.01); compared with the qizhi group, molding and drug four weeks CAM-2, VEGF no significant difference (P> 0.05); Withdrawal around four weeks CAM-2 had no statistical difference (P> 0.05), VEGF were significant difference (P< 0.05).3.2.3 Changes of nuclear transcription factor-KB in rats and the impact of Qibaipingfei CapsuleIn the prevention aspect:compared with the normal group, model group NF-kappa B average absorption optical density value increased significantly; compared with the model group, qiyu and qizhi group, lung tissue in rats of NF-group kappa B average optical density values decreased absorption. Compared with the normal group, model group were significant differences (P< 0.01). Compared with the qiyu group, niyu group suction optical density values increased, the difference was statistically significant (P< 0.01)From the aspect of treatment:compared with the normal group, model group NF-kappa B average absorption optical density value increased significantly; compared with the model group, qizhi and nizhi group NF- kappa B average optical density values decreased absorption, had no significant difference between qizhi group and nizhi group than in the normal group, model group, had significant difference (P< 0.01).3.2.4 Changes of ETA receptor and ETB receptor mRNA in rats lung tissue and the impact of Qibaipingfei Capsule3.2.4.1 Determination of the content results of ETA receptor mRNA level in rats lung tissueIn the prevention aspect:the results showed that, compared with the normal group, model group, qiyu group and niyu group of rat pulmonary artery ETA receptor mRNA gene expression increased significantly, the difference was statistically significant (P<0.01); compared with the model group, qiyu group, niyu group ETA receptor mRNA gene expression protein expression decreased obviously (P< 0.01), the difference was statistically significant; compared with the qiyu group, the expression of niyu group ETA receptor mRNA protein increased (P< 0.01 or P< 0.05).From the aspect of treatment:the results showed that, compared with the normal group, model group, qizhi group and nizhi group only ETA receptor mRNA protein in pulmonary artery of rats was increased significantly, the difference was statistically significant (P< 0.01); compared with the model group, rat pulmonary artery ETA receptor mRNA of qizhi group, nizhi group decreased expression (P< 0.01), the difference has statistical significance; and compared with the qizhi group, molding and drug four weeks and withdrawal around four weeks nizhi group ETA receptor mRNA protein were increased, the difference was statistically significant(P< 0.01).3.2.4.2 Determination of the content results of ETB receptor mRNA level in rats lung tissueIn the prevention aspect:The results show that, compared with the normal group, model group, qiyu group and niyu group rat pulmonary artery ETB receptor mRNA gene expression were decreased, the difference was statistically significant (P< 0.01 or P< 0.05); compared with the model group, qiyu group, niyu group ETB receptor mRNA protein expression was significantly increased (P<0.01), the difference was statistically significant; compared with the qiyu group, niyu group the expression of ETB receptor mRNA protein decreased (P< 0.01 or P< 0.05).From the aspect of treatment:the results showed that, compared with the normal group, model group, qizhi group and nizhi group ETB receptor mRNA protein expression were decreased, the difference was statistically significant (P< 0.01); compared with the model group, qizhi group, nizhi group rat pulmonary artery ETB receptor mRNA protein expression was significantly increased (P< 0.01), the difference has statistical significance; compared with the qizhi group, molding and drug four weeks and withdrawal around four weeks nizhi group the expression of ETB receptor mRNA protein decreased, but the difference was not statistically significant (P> 0.05).4 ConclusionQibai Pingfei capsule in the treatment of COPD rats with phlegm and blood stasis syndrome has significant clinical effect. Effectively improve the symptoms, physical signs of the rats,at the same time, significantly improve the Hemodynamics, pulmonary function; reduced serum cell factor endothelin-1 (ET-1), hypoxia inducible factor -1 alpha (HIF-1 alpha),vascular endothelial growth factor (VEGF) expression, increased the calcium regulated protein (CAM-2) expression; reduced the expression of NF-kappa B, reduced the rat lung tissue ETA receptor mRNA transcription and protein expression level, increased the rat lung tissue ETB receptor mRNA transcription and protein expression level.