Curcumin Inhibits The Proliferation Of Airway Smooth Muscle Cells In Airway Remodeling And Its Mechanism

Objective: Airway smooth muscle thickening is a well-documented pathological feature of the asthmatic airway. It has been found that to the large extent hyperplasia and /or hypertrophy of airway smooth muscle cells (ASMCs) contribute to the increase in muscle mass in remodeling airways of patients with moderate to grossly asthma, and significantly correlated with the thickness of the asthmatic airway wall. Between the two factors,hyperplasia of airway smooth muscle cells takes the predominant place. We established a model of proliferative airway smooth muscle cells in BALB/c mice to investigate inhibited effect of curcumin on hyperplasia of airway smooth muscle cells, and study its probable mechanism and drug targeting involved in this process. Methods: The model of the BALB/c mice was established by sensitizing and challenging with OVA. Activity condition of the mice was observed closely when challenged with OVA, the airway responsiveness was detected, OVA special immunoglobulin E (IgE) in the sera were detected by ELISA and the percentage of eosinophils in total Leukocyte in the bronchoalveolar lavage fluid (BALF) was measured. The changes of airway structure in the lungs were observed and the airway smooth muscle cells were identificated by immunohistochemistry. Thickness of airway wall, thickness of airway smooth muscle layer and number of smooth muscles were measured by IPP in the slides. Results: 1. The mice of model group presented positive symptoms such as dysphoria, tachypnea, salivating, abdominal spasm, incontinence of urine and excrement in the earlier stage. While the mice of preventing group and treating group with curcumin presented less symptoms later and relieved soon. The mice of normal group didn't present any symptom. 2. The airway responsiveness of the mice of preventing group and treating group with curcumin was lower than that of the mice of model group, P<0.05, but still higher than that of the mice of normal group, P<0.05. 3. OVA specific IgE in the sera of the mice of preventing group and treating group with curcumin was less than that of the mice of model group, P<0.05, but still more than that of the mice of normal group, P<0.05. 4. The percentage of eosinophils in total Leukocyte in the bronchoalveolar lavage fluid (BALF) of the mice of preventing group and treating group with curcumin was less than that of the mice of model group, P<0.05, but still more than that of the mice of normal group , P<0.05. 5. The thickness of airway wall ,the thickness of airway smooth muscle layer and the airway smooth muscle cells of the mice of preventing group and treating group with curcumin were less than those of the mice of model group, P<0.05, but still more than those of the mice of normal group, P<0.05. Conclusion:1. We had established the mouse airway remodeling model successfully. 2. Curcumin significantly reduces activity condition of mice, the airway hyperreactivity, dose of OVA specific IgE in the sera, the percentage of eosinophils in total Leukocyte in the bronchoalveolar lavage fluid (BALF) and reverses pathological changes. 3. Curcumin inhibits hyperplasia of airway smooth muscle cells in the airway remodeling model. 4. The inhibitory effect may be related to inhibiting activation of ERK signaling pathway induced by curcumin.