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OBJECTIVE To develop a 2-week cigarette smoke(CS)acute lung injury model exacerbated by haemophilus influenzae(NTHi)and study the protective effect of andrographolide in this COPD model.METHODS Female BALB/c mice,6-8-week-old,were exposed to 4% 3R4 FCS delivered using aperistaltic pump daily for 2 weeks to induce an acute lung injury model.After 2 weeks of smoking,mice were inoculated intratracheally with NTHi to induce exacerbation on the model.Mice were sacrificed 48 h after last bacteria challenge and lung samples were collected for various analyses.RESULTS After developing a 2-week CS acute lung injury model exacerbated by NTHi,the CS+NTHi group was shown to have a higher inflammatory response,higher bacterial clearance,an upregulation of MMP12 mRNA levels and decrease in TIMP1 mRNA levels in the lungs.Administration of Andrographolide suppressed BALF lung cellular infiltrates,TNF-α,CXCL1/KC,IL-1βand 8-OHdG protein levels,together with increased HO-1 and GR mRNA levels and decreased MMP-8 and MMP-9 mRNA levels.Andrographolide was able to ameliorate lung histopathology as observed with H&E staining and inflammation scoring.Andrographolide was also shown to reduce Keap-1 level in lungs without affecting DJ-1 level.CONCLUSION This study demonstrates the protective effect of andrographolide in a novel 2-week CS acute lung injury model exacerbated by NTHi and presents it as a potential therapeutic for COPD.
OBJECTIVE To develop a 2-week cigarette smoke (CS) acute lung injury model exacerbated by haemophilus influenzae (NTHi) and study the protective effect of andrographolide in this COPD model. METHODS Female BALB / c mice, 6-8-week-old, were exposed to 4% 3R4 FCS delivered using aperistaltic pump daily for 2 weeks to induce an acute lung injury model. After 2 weeks of smoking, mice were inoculated intratracheally with NTHi to induce exacerbation on the model. Rice were sacrificed 48 h after last bacteria challenge and lung samples were collected for various analyzes. RESULTS After developing a 2-week CS acute lung injury model exacerbated by NTHi, the CS + NTHi group was shown to have a higher inflammatory response, higher bacterial clearance, an upregulation of MMP12 mRNA levels and decrease in TIMP1 mRNA levels in the lungs.Administration of Andrographol suppressed BALF lung cellular infiltrates, TNF-α, CXCL1 / KC, IL-1βand 8-OHdG protein levels, together with increased HO-1 and GR mRNA levels and decrea sed MMP-8 and MMP-9 mRNA levels. Andrographolide was able to ameliorate lung histopathology as observed with H & E staining and inflammation scoring. Andrographolide was also shown to reduce Keap-1 level in lungs without affecting DJ-1 level. the protective effect of andrographolide in a novel 2-week CS acute lung injury model exacerbated by NTHi and presents it as a potential therapeutic for COPD.