Mechanism For Triterpene Acids Of Loquat. Leaf On The Therapy Of Chronic Bronchitis

Chronic Bronchitis(CB) is a common respiratory system disease whose clinical features are recurrent attacks of cough,expectoration or gasp.It has a very high attack rate and it can also lead to obstructive emphysema or even pulmonary artery hypertension as well as pulmonary heart disease.Currently,it is widely accepted that atmospheric contamination,infection and factors of hypersusceptibility have close relationships with the Chronic Bronchitis while the conditions of immune function play a more important role in the process of CB.Therefore,to regulate the disorder of neuroendocrine-immuno-function may the key method to prevent and cure the Chronic Bronchitis.At present,people pay more attention to anti-inflammatory,relieving cough on curing the disease,however,it is hard to find an effective medicine.On the other hand, medicines which improve the immune function of body,especially the traditional Chinese medicine,can prevent the course of aggravation through reducing the cytokines and mediators of inflammation.The leaf of Eriobotrya japonica(Thunb.)Lindl has a long history of medicinal use in China in a variety of inflammatory conditions especially CB therapy.According to our previous study,the triterpene acids extracted from Eriobotrya japonica(Thunb.)Lindl Leaf was the effective component and had therapy effect on chronic bronchitis.In addition,the characters of this medicine are the high performance and low toxicity.As a major effector of the innate immune system of the body,alveolar macrophage (AM) is the main source of cytokine,growth factor and oxygen free radical.Meanwhile, it is the principle cell whose functions are protection and adjusting in our lung.In our study,AM acts as the target on which we discuss the molecular mechanism of TAL on curing the CB.In this case it can provide the basement for the exploitation of new medicine on this field.Our previous research shows that intragastric administration of TAL can reduce the level of TNF-a,IL-8,IL-1 in tissue homogenate of lung and enhance the expression of IL-10,at the same time,the level of NF-κB and ICAM-1 in endothelial cell of air passage is inhibited.In addition,TAL can suppress free radical in AM of CB rats dramatically as well as the synthesizing and releasing of PGE2,LTB4 NO is a kind of multifunctional molecule which plays a significant role in the process of physiology and pathology in the respiratory system.Therefore it is important to research whether TAL has an effect on it.What's more,the molecular mechanism in cell-stimulating of AM is not very clear.As widely known that MAPK play a key role in inflammatory reaction,we use the AM and MAPK,as the researching platform and target respectively,to study the MAPK signal transduction pathway in AM and discuss the effect of TAL.It can help us to have a deep view in the molecular mechanism of the curing effect of TAL,meanwhile,we can get the basement for the research of the new medicine.The main content is divided into three sections as follows: 1 The effect of triterpene acids of Eriobotrya japonica(Thunb.)lindl.leaf on the expression of iNOS and production of NO in alveolar macrophage of chronic bronchitis rats.Establishing the model of CB rats by using BCG plus LPS,a week later,the intragastric administration of TAL was operated.Consequently,we investigate the effect of Triterpene Acids of Eriobotrya japonica(Thunb.)Lindl.Leaf(TAL) on the iNOS and the production of NO in alveolar macrophages(AM) of chronic bronchitis (CB) rats and the mechanism related to anti-inflammatory action.The results show that TAL can reduce the expression of iNOS and release of NO in AM of CB rats,it may be one of the mechanism of the preventive and therapeutic effect in chronic bronchitis. 2 MAPK signal transfluction pathway in AM of CB ratsInhibitors of PTK,PI₃K,Akt and PKC were used to detect correlated signal protein of MAPK before transcription in AM of CB rats.PKC,PI₃K/Akt,phosphorylation were reduced after treatment with inhibitors of PTK.LY294002,the inhibitor of PI₃K suppressed PI₃K and Akt phosphorylation but increased p38 and JNK phosphorylation. ERK phosphorylation was decreased by Calphostin C,an inhibitor of PKC,However,it has no effect on the phosphorylation of p38 and JNK.According to our results,the LPS-induced MAPK signal pathway in AM of CB rats may be PTK---- PI₃K/Akt----JNK/p38 or PTK----PI₃K----PKC----ERK.3 The effect of TAL on MAPK activation.Further research suggested that TAL can reduce the phosphorylation of PKC,p38, JNK and ERK while it almost has no effects on PI₃K as well as Akt.TLR4 receptor expression in AM of CB rats was highly increased when stimulated by LPS,however, TAL can not decrease its production.In conclusion,action of TAL on MAPK in AM may be happened on downstream of PI₃K.