Study On The Effect Of DEHP On Rat Asthma Model

Asthma is a chronic airway inflammation, which is characterized by inflammatory cells recruitment in airway, airway hyperresponsiveness and airway remodelling. In all diseases, asthma causes the second large group of death or disabling worldwide, only after cancer. There are more patients in developed countries and in children and teenagers than other areas and ages. In traditional opinion, some substances in nature such as pollen, pet hair and mould is the environmental factor that cause asthma. But, recently many researchers are focusing on the relationship between man-made chemicals and the growing incidence of asthma. Asthma caused by substances in nature and man-made chemicals have different mechanisms. DEHP (di-(2-ethylhexyl) phthalate) is a common pollutant in modern life, and it is easily found in indoor environments. DEHP can enter human body by food, water and air. The hereditarytoxicity and estrogen effect of DEHP are confirmed. Recently, some researches indicate DEHP can induce or aggravate asthma. We explored the relationship between DEHP and asthma by using a rat asthma model and rat ASM (Airway smooth muscle).1. Effect of DEHP on rat asthma modelWork-related asthma (WRA) is an important aspect of new asthma. In animal asthma model, we compare effect of DEHP on health rats and OVA-immunized rats. DEHP is injected into lung via airway to simulate the 8h work environment that has 0.5mg/m3 or 5mg/m3 DEHP in the air. The exposure lasts one month. In cell asthma model, we compare effect of DEHP on ASM in a standard culture medium and culture medium added 10-5g/L IL-4 to simulate asthma symptom.OVA-immunized rats have significant difference compared with control rats in airway hyperresponsiveness test, IL-4 dose in lung and airway remodelling. ASM in the culture medium with IL-4 have significant difference compared with control ASM in growth rate. Hypertrophic and hyperplastic growth of ASM is important in the overall remodelling response. Health rats and ASM exposed to DEHP do not have such difference compared with control. OVA-immunized rats exposed to 5mg/m DEHP showed more severe asthmatic pathological changes than the OVA-immunized rats without DEHP exposure. But hyperplastic growth of ASM induced by IL-4 is no difference, no matter 3μmol/L DEHP added to culture medium or not.In a word, DEHP do not induce asthma by itself, but DEHP exposure causes more severe asthmatic pathological changes in OVA-immunized rats.2. Possible role that DEHP plays in asthmaOVA can induce allergic asthma, but DEHP can not. As a chronic airway inflammation, allergic asthma needs both allergen and atopy. DEHP is not an allergen, so it can not induce asthma as OVA. DEHP may have effect on asthma in the aspect of atopy. Atopy is a disorder state of immune system. It can be caused by both inheritance and environment stimulator. If it is caused by environment stimulator, we call it acquired atopy and the environment stimulator is atopy excitationsource. Our research supports acquired atopy theory. DEHP is considered as an atopy excitationsource.In detail, Hypertrophic and hyperplastic growth of ASM is important in the overall remodelling response, and then cause airway hyperresponsiveness. Cytokines and chemokines released by other cells in asthma can induce hypertrophic and hyperplastic growth of ASM. If DEHP can affect the response of ASM to those cytokines and chemokines, DEHP can contribute to airway remodelling and airway hyperresponsiveness. Although we find hyperplastic growth of ASM induced by IL-4 is no difference, no matter 3μmol/L DEHP added to culture medium or not. We confirm IL-4 can induce ASM hyperplastic growth, and we also see IL-4 dose in lung has a significant rise in OVA-immunized rats exposed to 5mg/m3 DEHP compared with OVA-immunized rats without DEHP exposure. So DEHP may not affect the response of ASM to IL-4 directly. It may affect other cells in lung to increase IL-4 dose. And IL-4 is only one of the long list of cytokines and chemokines that can induce hypertrophic and hyperplastic growth of ASM. Further researchs are required to discover the relationship between DEHP and other cytokines and chemokines.DEHP shows toxicity to ASM in the research. And ASM is more sensitive to DEHP than those cell clones in common use (such as HeLa cell). We can imagine that DEHP can cause cell damage when it comes into the lung and contacts with cells like epithelium. And epithelium damage can lead to a series of inflammation response, and then induces acquired atopy.