Effect Of Substance P On Airway Resistance In Asthmatic Rats And The Treatment Of Procaterol Hydrochloride

IntroductionBronchial asthma is a chronic airway inflammatory disease, which is participated by many cells(such as eosinophils,mast cell,T lymphocyte,neutrophil and epithelium)and cellular elements,and also asthma continues to be a major health problem worldwide. Its mechanism include chronic airway inflammation,airway responsiveness,airway remolding,nervous system,allergic reaction and genetic problems, and they react with each other, however, the mechanism remains unknown. It is well known to us that its characters is chronic airway inflammation,airway hyperresponsiveness and airway remolding.Recent study have shown that the infiltration of eosinophils,T lymphocyte and monocyte cause epithelium,mucous secretion,vascular leakage and the airway epithelial damage in asthma exposes sensory nerves. Barnes posed a conception called axon reflex involved in the mechanism of asthma, which makes the relationship of nervous system and immune system being got attention. They can react with each other, and peptide may play an important role during this process.Up till now, almost 20 kinds of peptide have been determined in the airway, and sensory peptide is just one of them, substance P is an important peptide leading to neurogenic inflammation in the airway.It is a small peptide released by sensory nerve ending,there are much evidence that substance P has potent effect on neurogenic inflammation, including smooth muscle contraction, increase in vascular permeability,plasma exudation,vasodilatation and edema,mucus secretion,which are similar to the pathogenesis of asthma.Airway hyperreactivity (AHR) is an important characteristic feature of asthma. Recently, it has been recognized that airway inflammation underlies the phenomenon of AHR. Previous study showed that the increased parasympathetic nerve reaction is the main cause of AHR, but there is now convincing evidence that there is still non-cholinergic and non-adrenalin nerve besides classic cholinergic and adrenalin nerve, which include excitatory nerve fiber (e-NANC) and inhibitory nerve fiber (i-NANC).The excitatory nerve fiber in the lung is mainly sensory nerve,whose ending can release tachykinins such as substance P (SP),neurokinin A (NKA),neurokinin B (NKB) and calcitonin gene-related peptide (CGRP),which has potent effect on airway inflammation, including smooth muscle contraction, increase in vascular permeability and mucus secretion. Besides, substance P (SP) also has potent effect on airway inflammation,and SP immunoreactive nerves in the airway have been found within the airway smooth muscle and surrounded the blood vessels. The experiment in vitro showed that substance P (SP) can stimulate the mast cell to release inflammatory transmitter, enhance the effect of leukotriene and stimulate the contraction.Meanwhile,the airway inflammation can also promote the release of substance P (SP).When the airway epithelium is damaged,the inflammatory transmitter has effect on the exposed sensory nerve ending and cause the release of substance P (SP) by axon reflex,and amplify the airway inflammation,furthermore it may contribute the development of the airway neurogenic inflammation and AHR. Previous study showed that substance P (SP) participate in the pathogenesis of asthma by the effect of smooth muscle contraction,vascular permeability mucus secretion and inflammatory cell activation,while,this study is to explore the effect of Substance P on airway resistance in asthmatic rats and the treatment of Procaterol Hydrochloride,the solution of these questions will make us know the relationship of substance p and asthma,and may contribute new drugs that inhibit neurogenic inflammation in the airway.MethodsAnimals sensitized were injected intraperitoneally with OVA together with aluminum hydroxide,and were challenged by inhalation of 1%OVA.The Airway Resistance of rats was measured with AniRes2005 pulmonary function meter,total numbers of leukocyte in the bronchoalveolar lavage fluid were determined and a differential cell count was determined, the expression of Eotaxin was investigated by immunohistochemical method and analyzed by image analysis system.Results1.The results of airway resistanceThe concentration-response curve to Ach in the asthmatic rats is remarkably moved,and the inspiratory resistance(Ri) and the expiratory resistance(Re) are obviously higher than those in normal control rats (P<0.05), which show that the response to Ach in the asthmatic group is increased when compared to the normal group, and also show that the asthmatic model is successful. Whereas,the airway resistance in the Substance P group are obviously higher than those in the asthmatic rats (P<0.05), but the airway resistance in the procaterol hydrochloride group is higher than those in normal control rats,but lower than those in the asthmatic rats (P< 0.05)2.The results of numbers of total and differential cell counts in BALFThere are significant increases in numbers of total and differential cell counts in BALF in substance P group when compared with asthma group (P<0.05), while,there are significant increases in numbers of total and differential cell counts in BALF in asthmatic group when compared with control group (P<0.05).Whereas, there is significant decrease in numbers of total and differential cell counts in BALF in procaterol hydrochloride group when compared with asthma group(P>0.05)3.The expression of Eotaxin in lungThe expression of Eotaxin in normal group was 0.2788±0.0020,The expression of Eotaxin in asthma group was 0.2678±0.0076,but the expression of Eotaxin in substance P group was 1.1499±0.1150, higher than that in asthma group.Conclusion1.Substance P can increase the airway in asthmatic group, and participate in the process of AHR, thus has a close relationship with asthma.2. Substance P can promote the release of inflammation cells(neutrophil lymphocyte,monocyte,macrophage and Eos) in the BALF, which may be involved in the pathogenesis of asthma. 3. Substance P can increase the expression of Eotaxin, which participate in the process of airway neurogenic inflammation.4. Procaterol Hydrochloride can decreased the AHR caused by Substance P, which is an effective pathway to treat asthma.