The Role Of Mitochondrial Damage In Bronchial Asthma Pathogenesis

Bronchial asthma is a complex, inflammatory disorder accompanied with airflowobstruction of variable degrees, bronchial hyper-responsiveness, and airway inflammation.Asthma is caused by a combination of environmental factors and inflammatory stimuli.Recently, several studies found that mitochondrial function and the pathogenesis of asthmaare closely linked; they found that mitochondrial dysfunction plays an important role in theairway inflammation of asthma. Then, what will happen on mitochondrial in asthma? Inthis study, we will illustrate the changes of mitochondrial structure and the role of changesin asthma by the observation of mitochondrial ultra structure and asthma animal model.Mitochondrion is an important organelle in cells. It was considered to be an importantEnergy generator in cells and play an important role in producing ATP.Besides;mitochondria perform several cellular functions in many other physiological processes,including glucose metabolism, intracellular calcium regulation, and the production of ROSand cell apoptosis. Well, how does it regulate the cytoplasm calcium signals and reactiveoxygen? Several studies have shown that in the physiological state, mitochondrial regulateintracellular calcium concentration by release and uptake pathway. Cytoplasm of calciumhomeostasis is important to maintain the normal physiological activity of the cells. Whenthe outsider’s inflammation leads to mitochondrialdestruction, intracellular calciumhomeostasis will destroy calcium concentration changes. In this study, we will measure thechange in the concentration of [Ca2+]iin inflammatory stimuli to explore the relationshipbetween [Ca2+]Iand inflammation. Meanwhile, mitochondrial damage was positivelycorrelated with the content of the active oxygen, outside inflammation leads to the releaseof a variety of free radicals; they will damage the mitochondria, lead to the change of mitochondrial ultra structural, and the damaged mitochondria will produce an excess ofreactive oxygen species by oxidative phosphorylation. In this study, we will measure theconcentration of reactive oxygen species on the effect of cell ciliary beat frequency toreflect the relationship of intracellular ROS and inflammation.ObjectiveIn this study, we use ovalbumin-induced rat asthma model and detect the inflammatoryresponse. To illustrate the role of mitochondrial damage in bronchial asthma, we useelectron microscopy to detect the extent of the damage of mitochondria; we will illustratethe mechanism of mitochondrial damage in bronchial asthma through detection of reactiveoxygen species and [Ca2+]Iconcentration and the cell ciliary beat frequency stimulated bydifferent concentrations of reactive oxygen species.Methods:1. Establish the chronic models of allergen exposure by using OVA, The ventilatorand multi channel physiological signal recorder are used to record bronchialhyper-responsiveness, confocal microscopy is used to record the CBF (ciliary beatfrequency), Swiss dyeing is used in eosinophil count, Elisa reagent kit is used to measurethe inflammatory factor level, HE staining is used to observe the morphology of lungtissue;2. Observe the mitochondrial ultra structure by electron microscopy;3. Stimulate airway epithelial cells with IL-4and use confocal microscopy to measureintracellular calcium level and ROS level. Cells were stimulated with differentconcentrations of reactive oxygen species and measuring the cilia beat frequency.Results:1. Compared with control group, airway reactivity in asthma rats was significantlyhigher (P<0.05); structural remodeling of the airway, tracheal wall was significantly thicker(P <0.05), and the wall is surrounded by a large number of inflammatory cells; trachealepithelial ciliary beat frequency is reduced (P <0.05); eosinophil cell count increased significantly (P <0.05); plasma IL-8and TNF-content in plasma was significantly higher (p<0.05). These results indicate that inflammatory reaction occurs in asthma rats;2. Compared with control group, the mitochondrial ultra structures in asthma rats havesignificantly destruction and swelling phenomenon. This result indicates that mitochondrialstructure was damaged and the damaged mitochondrial play an important role in thepathogenesis of asthma;3.Compared with control group, the active oxygen content and concentration of [Ca2+]Iin IL-4stimulated airway epithelial cells is significantly higher (P<0.05),the cilia beatfrequency in IL-4stimulated airway epithelial cells is significantly lower (P<0.05), ciliabeat frequency decreases with increasing active oxygen (P<0.05).Conclusions:Taken together these results show that mitochondrial structure significantly destroyed inasthma, the damaged mitochondrial would lead to the release of [Ca2+]Iand the productionof ROS, the release of large amount of reactive oxygen species will lead to the reduction ofciliary beat frequency, it unable to maintain the normal physiological functions of therespiratory, which will further aggravate the inflammation, leading to delayed healing ofasthma.