Studies On The Molecular Pathophysiology Of Hyper-sensitive Asthma Induced By Indoors Formaldehyde

Formaldehyde (FM) is an occupational and general indoor hazard often affecting the respiratory airways. One of the main causes of multiple chemical sensitivity (MCS) is gaseous FM, and MCS has become an important social problem in the developed countries. Domestic exposure to formaldehyde increases the risk of childhood asthma. Building and furnishing materials and consumers products are important sources of formaldehyde and other volatile organic compounds (VOCs) in the indoor environment. The emission from materials is usually continuous and may last for many years in a building. VOCs can cause adverse health effects to the building occupants and may contribute to symptoms of sick building syndrome (SBS), such as attention difficulty, headache, cough, breathing difficulty, asthma.Formaldehyde, a major air pollutant in the furnished home, may elicit the hyper-sensitive asthma through immunity-abnormality reaction mechanism, airway neurogenic inflammation mediated by capsaicin receptor and their co-operated mechanism. The immediate asthmatic reaction (IAR) and the late asthmatic reation(LAR) emerges in early and late-phase responses to allergen. And the hyper-sensitive asthma is a chronic disease which is few cured. From the molecular pathophysiology of asthma, novel Chinese drug can be explored to approach to this chronic and consumptive disease.This studies includes four aspests as followed:Firstly, the gaseous formaldehyde induced airway neurogenic inflammation may be that formaldehyde actives the NMDA-receptor or/and VR1. This may be the neuro-receptor mechanism of airway neurogenic inflammation.Secondly, in this study we primarily confirmed that vanilloid receptors (VR) distributed in sensory neuron are the triggering target bio-molecule of airway irritation induced by formaldehyde.Thirdly, successive formaldehyde expoure may increase cytokine NGF expression, and NGF upregulates chemosensitive receptor VRl synchronously. This may have implications for the nervous central neuro-immunological mechanisms mediating multiple chemical sensitivity (MCS), sick building syndromes (SBS), bronchial hyperresponsiveness (BHR), and asthma in humans.At last, successive formaldehyde exposure may increase NGF expression in rat brain stem, and curcumin (a pharmacological inhibitor of the JNK-AP-1 pathway) resulted in a decrease expression of NGF gene. This may be a new horizon for curing MCS, SBS, BHR and asthma in human.Chapter 1 The neuro-receptor mechanism of airway neurogenic inflammation induced by gaseous formaldehydeAbstract: To explore the neuro-receptor mechanism of airway neurogenic inflammation. Methods: SP concentration in respiratory organ of gaseous formaldehyde exposed mice with or without different receptor antagonist pre-injected was measured by radioimmunoassay. Results: 1. It was found that the SP concentration in respiratory organ of 2.42mg/m3 formaldehyde exposed group (30.89±3.59pg/0.3ml) was significantly higher than the air exposed group (24.34 ± 3.18 pg/0.3ml)(p<0.05). 4.81mg/m3 formaldehyde exposed group (34.71 ± 5.73pg/0.3ml) was significantly higher than the air exposed group (24.34 ± 3.18pg/0.3ml)(p<0.01). 2. The SP concentration in respiratory organ of 2.42mg/m3formaldehyde exposed group pre-injected with NMDA-receptor antagonist MgSO4 (16.51±5.80pg/0.3ml) was significantly lower than the 2.42mg/m3 formaldehyde exposed group (30.89 ± 3.59pg/0.3ml)(p<0.01). 3. The SP concentration in respiratory organ of 2.42mg/m3 formaldehyde exposed group pre-injected with VR1 antagonist capsazepine (16.51 ±5.80pg/0.3ml) was significantly lower than that of the 2.42mg/m3 formaldehyde exposed group (30.89 ± 3.59pg/0.3ml)(p<0.01). Conclusions: It is suggested that the gaseous formaldehyde induced airway neurogenic inflammation may be that formaldehyde actives the NMDA-receptor or/and VR1. This may be the neuro-receptor mechanism of airway neurogenic inflammation...