Effect And Intervention Study Of Modified Erchentang On Pulmonary Vascular In Rat With Chronic Obstructive Pulmonary Disease

ObjectiveThe research aimed to the effect and molecular mechanism of Modified Erchentang in rat with Chronic Obstructive Pulmonary Disease.MethodsSeven kinds of randomized group contained blank group,model group,Erchentang(5 g·kg^-1·d^-1)group,Modifide Erchentang of low?10g·kg-1·d-1?,moderate?20g·kg-1·d-1?and high dosage?40g·kg-1·d-1?group,compound manshanhong syrup group with ten SD rats in each group.The methods including using lipopolysaccharide?LPS?instillation in the rat's tracheal and fumigating rat were adopted to prepare COPD rat model and the preparation result was judged by lung pathological and function change situation.After the successful preparation,Erchentang,Modifide Erchentang and manshanhong syrup were respectively imposed on rats in corresponding group using gavage method.Recorded each rat's weight,coat color and cough asthma situation and the judgement about rat's lung function adopted indexes such as content index of peak expiratory flow and tidal volume accordding to the grouping condition daily.Enzyme-Linked ImmunoSorbent Assay?ELISA?was used to determine the content of IL-4 and IL-1?in rat's serum,bronchoalveolar lavage fluid existing in rat's bronchial and lung tissues.Immunohistochemistry?IHC?was used to test the expression of Vascular endothelial growth factor?VEGF?,Vascular Endothelial Growth Factor Receptor-2?VEGFR2?,Endothelin1?ET-1?,Sirt1.Also,the pathological structure change of pulmonary vessels and tissue was inspected by light microscope.ResultsCompared with control group,the level of peak expiratory flow and tidal volume increase significally in the model group rat's content index?P<0.01?.Meanwhile,the level of IL-4 and IL-1?'s content contained in rat's serum,bronchoalveolar lavage fluid existing in rat's bronchial and lung tissues increase significally?P<0.01?.Also the expression of VEGF,VEGFR2 and ET-1 increase significally in model group lung tissues?P<0.05?,while the expression of Sirt1 protein decrease dramaticlly?P<0.05?.In comparison with model group,there is a pronounced increase?P<0.01?in Modifide Erchentang of low,moderate and high dosage group rat's content index of peak expiratory flow and tidal volume,while the IL-4 and IL-1?'s content contained in rat's serum,bronchoalveolar lavage fluid existing in rat's bronchial and lung tissues reduce?P<0.01?obviously,there is greater drop in Modifide Erchentang of moderate group at the same time.In addition,there is a remarkable reduction?P<0.05?in Modifide Erchentang of high,low group's expression of VEGF,VEGFR2 and ET-1,while the Sirt1 protein's expression increases?P<0.05?dramaticlly.Compared with Erchentang(5 g·kg^-1·d^-1)group and manshanhong syrup group,the level of peak expiratory flow and tidal volume increase significally in modified Erchentang of middle dosage group,and the level of IL-4 and IL-1?'s content contained in rat's serum,bronchoalveolar lavage fluid existing in rat's bronchial and lung tissues reduce significally?P<0.05?,the expression of VEGF,VEGFR2 and ET-1 protein reduce dramaticlly?P<0.05?,the expression of Sirt1protein increase significally.Pathological changes:In the eye view,the lung of the contral group rat has smooth surface and bloom color,while the model group has rough surface and dark red color.In the microscopic view,the lung structure of the contral group is complete,no significantly in the capillary and bronchiole,no inflammation cells aggregation,no tube wall fibroplasia,while the vascular tupe muscularizes and narrows apparently for the reason that the model group rat's lung tissue vascular tupe wall smooth muscle cells has hyperplasia with significant increase in extracellular matrix.In contrast to model group,Modified Erchentang of middle dosage group's vascular tupe wall smooth muscle cells has less hyperplasia with significant decrease in extracellular matrix and inflammatory cells almost disappeares.In conclusion,Modified Erchentang of middle dosage group's symptoms improvement conditions is superior to Modifide Erchentang of low?10g·kg-1·d-1?,high dosage?40g·kg-1·d-1?group,Erchentang(5 g·kg^-1·d^-1)group and compound manshanhong syrup group.Conclusions1.Modified Erchentang can significantly improve flow limitation and lung function and protect lung tissue in rats,the pathological changes of lung tissue as evidence.2.Modified Erchentang can be effective in the treatment the inflammatory reaction of lung tissue by decreasing the level of IL-1??IL-4 in rat's serum,bronchoalveolar lavage fluid existing in rat's bronchial and lung tissues.3.Modified Erchentang can slow down the progression of COPD and its pathogenesis by inhibiting the expression of VEGF?VEGFR2?ET-1 to prevent pulmonary vascular remodeling.