The Effects Of Cannabinoid Receptor On OVA-induced Airway Remodeling In Rats

Objective:(1)To study the effects of cannabinoid CB2 receptor agonist JWH133 and inhibitor SR144528 on OVA-induced airway remodeling in rats.Methods : Thirty-two Famale SD rats were radomly divided into 4 groups(n=8),Group A: blank control group;group B: airway remodeling;group C: airway remodeling +JWH133;group D: airway remodeling + SR144528.Using ovalbumin(OVA)to sensitize and challenge to establish asthmatic rat model.Group C and group D were injected JWH133(2.5mg/kg)and SR144528(2.5mg/kg)30 minutes before each atomization in the last four weeks of sensitization.Observed pathological changes of lung tissue by HE staining and Masson staining.Matrix metalloproteinase-9(MMP-9)、Matrix metalloproteinase-2(MMP-2)and vascular endothelial growth factor(VEGF)were measured via bronchoalveolar lavage fluid(BALF)by ELISA.MMP-9、MMP-2、VEGF protein level was determined by Western bloting.Results:(1)HE staining show that in the lung tissue of group of blank tars,we can find that the lung tissues have clear structure and intact alveolar,no obvious alveolar congestion and bleeding,a little neutrophil infiltration was found in the airway and vascular wall,and the lung injury score was low.Compared with group of blak rats,the lung tissues in group of airway remodeling rats have disordered structure and ruptured alveoli,obvious alveolar congestion and bleeding,a lot of neutrophil infiltrations were found in the airway and vascular wall,and the lung injury score was heavy.Compared with group of airway remodeling rats,the lung tissues of airway remodeling +JWH133 rats have clear structure and intact alveolar,no obvious alveolar congestion and bleeding,a little neutrophil infiltration was found in the airway and vascular wall and the lung injury score was low have significantly increased(P<0.01).Compared with group of airway remodeling rats,he lung tissues of airway remodeling+SR144528 rats have disordered structure and ruptured alveoli,obvious alveolar congestion and bleeding,a lot of neutrophil infiltrations were found in the airway and vascular wall,and the lung injury score was heavy,and there was no significant difference(P>0.05).(2)Masson staining show that the blue collagen fibers in group of blak rats had no obvious collagen deposition in alveolar septum and alveolar cavity.Compared with group of blank rats,the group of airway remodeling rats had significant collagen deposition in alveolar septum and alveolar cavity.Compared with group of airway remodeling rats,the group of airway remodeling +JWH133 rats had little collagen deposition in alveolar septum and alveolar cavity.Compared with group of airway remodeling rats,the group of airway remodeling+SR144528 rats had significant collagen deposition in alveolar septum and alveolar cavity.(3)Elissa results: the concentration of MMP-2 in BALF of each group was significantly higher than that of the blank control group(0.9 0 ± 17),airway remodeling group(1.78 0 ± 34),airway remodeling + jwh133 group(1.07 0 ±41),airway remodeling + sr144528 group(1.78 0 ± 0.44)。 The concentration of MMP-9 in BALF of rats in each group was significantly higher than that in the blank control group(0.56 0 ± 36),airway remodeling group(1.04 0 ± 2)Airway remodeling + jwh133 group(0.52 2 ± 36),airway remodeling + sr144528 group(1.31 0 ± 0.55)。 The concentration of VEGF in BALF of rats in each group was significantly higher than that in blank control group(0.95 0 ± 24),airway remodeling group(1.75 0 ± 41),airway remodeling + jwh133 group(1.14 0 ± 58),airway remodeling + sr144528group(1.87 0 ± 0.68)。 Compared with the blank control group,the concentrations of MMP-9,MMP-2 and VEGF in BALF in the airway remodeling group were significantly higher(P < 0.01).Compared with airway remodeling group,the concentrations of MMP-9,MMP-2 and VEGF in BALF in airway remodeling + jwh133 group were significantly lower(P < 0.01).Compared with airway remodeling group,the concentrations of MMP-9,MMP-2 and VEGF in BALF in airway remodeling + sr14452 group were increased,and the difference was not significant(P > 0.05).Western blot was used to detect the protein expression of MMP-9,MMP-2 and VEGF in lung tissue of rats in each group.The results showed that compared with the blank control group,the protein expression of MMP-9,MMP-2 and VEGF in lung tissue of rats in airway remodeling group was higher,and the difference was statistically significant(P < 0.01).Compared with airway remodeling group,the expression of MMP-9,MMP-2 and VEGF in lung tissue of airway remodeling +jwh133 group was significantly decreased(P < 0.01).Compared with the airway remodeling group,the expression of MMP-9,MMP-2 and VEGF in the lung tissue of the airway remodeling + sr144528 group was higher,and the difference was not statistically significant(P > 0.05).(2)Conclusions:In this study,cannabinoid receptor agonists and inhibitors were used to intervene the airway remodeling induced by ova in rats,which provided a new idea for the treatment of airway remodeling.In this study,cannabinoid receptor agonist JWH133 attenuates lung injury in rats with airway remodeling,regulates the levels of MMP-9,MMP-2 and VEGF in rats,reduces the deposition of extracellular matrix in lung tissue,and inhibits the airway remodeling induced by ova.