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비만 유도 마우스 천식 모델에서 면역반응에 대한 magnesium과 corticosteroid의 효과

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비만 유도 마우스 천식 모델에서 면역반응에 대한 magnesium과 corticosteroid의 효과 고려대학교 의과대학 대학원 의학과 문준동 (지도 : 홍윤식 교수) - Abstract - Magnesium and corticosteroid effect on immunologic response in obesity-induced murine asthma model Jundong Moon, M.D. Major in Emergency Medicine, Department of Medical Science, Graduate School of Korea University, Seoul, Korea (Director: Prof. Yun Sik Hong, M.D., Ph.D.) Background: Magnesium deficiency in obesity is commonly reported and low magnesium level is known to aggravate chronic low grade inflammation in obesity. We hypothesized that magnesium as a known adjunct therapy for severe uncontrolled asthma exacerbation might have different immunologic effects on obese asthma compared with non-obese asthma. Objective: This study aimed to investigate the effects of magnesium co-administration with dexamethasone on the airway inflammation in obese mice. Method: Female C57BL/6 mice were fed for 12 weeks with high fat diet to induce obesity. On days 120 and 127, mice were sensitized to ovalbumin(OVA) and then challenged with aerosolized OVA or phosphate-buffered saline(PBS) on days 134, 135 and 136. After OVA challenge, dexamethasone (3mg/kg, po) with or without magnesium sulfate (100mg/kg or 200mg/kg, ip) was administrated. The inflammatory cells and cytokines in bronchoalveolar lavage fluid, leptin. total IgE and OVA specific IgE in serum, goblet cell ratio, airway wall thickness and airway smooth muscle area from lung tissue were evaluated as 48h after last OVA challenge. Result: PBS treated obese group displayed higher eosinophil and lymphocyte count in bronchoalveolar lavage fluid than PBS treated control group, but level of IL-4, IL-6, IL-13, total IgE, OVA specific IgE and goblet cell ratio, airway all thickness, airway smooth muscle area were not different between the two groups. The response of dexamethasone was blunted in high fat diet group versus control group, as showed not significantly reduced IL-4, IL-6, total IgE, OVA-specific IgE level and airway wall thickness. Magnesium co-administration with dexamethasone in obese group decreased IL-13 (regardless of magnesium dose), airway smooth muscle area (low dose, 100mg/kg), total IgE and OVA specific IgE (high dose, 200mg/kg), compared with high fat diet group administrated with dexamethasone only, which findings were not observed in control group. Conclusion: In addition to reported bronchodilating effect, magnesium co-administration shows weak immunosuppression effect and attenuates airway smooth muscle cell proliferation in obese group compared with normal weight group.

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서론 ‥‥‥‥‥‥‥‥‥‥‥‥‥‥‥‥‥‥‥‥ 1
연구방법 ‥‥‥‥‥‥‥‥‥‥‥‥‥‥‥‥‥‥ 4
결과 ‥‥‥‥‥‥‥‥‥‥‥‥‥‥‥‥‥‥‥‥ 9
고찰 ‥‥‥‥‥‥‥‥‥‥‥‥‥‥‥‥‥‥‥‥ 12
결론 ‥‥‥‥‥‥‥‥‥‥‥‥‥‥‥‥‥‥‥‥ 18
참고문헌 ‥‥‥‥‥‥‥‥‥‥‥‥‥‥‥‥‥‥ 19
개요(abstract) ‥‥‥‥‥‥‥‥‥‥‥‥‥‥‥ 41

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