OBJECTIVE

2

To study the effects and potential mechanism of wogonin （Wog） on airway inflammation in rats with chronic obstructive pulmonary disease （COPD）.

METHODS

2

Eighty-four rats were randomly divided into control group， model group， Wog low-dose and high-dose groups （intragastric administration of 50， 100 mg/kg）， aminophylline group （positive control， intragastric administration of 2.3 mg/kg）， recombinant rat receptor-interacting protein kinase 1 [rRIPK1， receptor-interacting protein kinase 1 （RIPK1） activator] group （tail vein injection of 8 µg/kg）， and Wog high-dose+rRIPK1 group （intragastric administration of Wog 100 mg/kg+tail vein injection of rRIPK 8 µg/kg）， with 12 rats in each group. Except for control group， COPD model of other groups was induced by smoking combined with tracheal injection of lipopolysaccharide. Twenty-four hours after successful modeling， the rats were administered once a day for 4 weeks. The changes of peak inspiratory flow （PIF）， peak expiratory flow （PEF） and minute ventilation （MV），forced expiratory volume in one second（FEV

1

）/forced vital capacity（FVC） were measured after the last medication； the serum levels of interleukin 1β（IL-1β）， IL-6 and tumor necrosis factor-α （TNF-α） were measured by ELISA； the pathological changes of lung tissue in rats were observed； the apoptotic rate of pulmonary epithelial cells was detected. mRNA expressions of RIPK1， RIPK3 and mixed lineage kinase domain-like protein （MLKL）， and protein expressions of RIPK1， RIPK3 and p-MLKL were all detected in lung tissue of rats.

RESULTS

2

Compared with control group， PIF， PEF， MV and FEV

1

/FVC of model group were decreased significantly （

P

＜0.05）， while the levels of IL-1β， IL-6 and TNF-α were increased significantly （

P

＜0.05）； there was a large number of inflammatory cells infiltration in the lung tissue and bronchial wall thickening in model group； the apoptotic rate of pulmonary epithelial cells，mRNA expressions of RIPK1， RIPK3 and MLKL， protein expressions of RIPK1， RIPK3 and p-MLKL were increased significantly （

P

＜0.05）. Compared with model group， above indexes of rats were improved significantly in Wog low-dose and high-dose groups （

P

＜0.05）， and pathological injuries were alleviated significantly. The corresponding indexes of rats were worsened in rRIPK1 group （

P

＜0.05）， and pathological damage had further worsened. rRIPK1 significantly attenuated the inhibitory effect of high-dose Wog on airway inflammation and RIPK1/RIPK3/MLKL pathway in COPD rats （

P

＜0.05）.

CONCLUSIONS

2

Wog may improve airway inflammation in COPD rats by inhibiting RIPK1/RIPK3/MLKL signal pathway.