Objective

2

To analyze the effect of

Qingfei Litan Formula

（清肺理痰方， QLF） in treatment of

Klebsiella pneumoniae

-induced acute lung injury （ALI） in mice model and to explore the potential mechanism.

Methods

2

Totally 108 BALB/c mice were randomly divided into 6 groups， control group， model group， ceftriaxone sodium group， QLF low， medium， and high-dose groups， with 18 mice in each group. Tracheal instillation of

Klebsiella pneumoniae

（1.04×10

9

CFU） was used to replicate the ALI model in mice of all groups except for blank group. After the models were established， ceftriaxone sodium liquid at a single dose of 200 mg/kg was given to the mice through tail vein injection in the ceftriaxone sodium group； QLF liquid at a dose of 1.0 g/kg， 2.0 g/kg and 4.0 g/kg was given by gavage to the low， medium and high dose QLF group， respectively； the model group and the control group were given normal saline for injection at 10 mg/kg by gavage； the interventions were administered for four times at 0 h， 24 h， 48 h and 72 h after modeling. The body weight was observed at 0 h， 24 h， 48 h， 72 h， and 96 h after modeling. After the last administration， the blood routine indicators including white blood cells （WBC）， neutrophils （NEU）， lymphocytes （LYN）， inflammatory factors interleukin-1β （IL-1β）， tumor necrosis factor-α （TNF-α）， interleukin-6 （IL-6）， and myeloperoxidase （MPO） level in the serum， alveolar lavage fluid and lung tissues， as well as lung function indicators including total lung resistance （RL）， lung outflow resistance （Re）， lung dynamic compliance （Cydn）， peak expiratory flow rate （PEF） and maximum ventilation （MVV）） were assessed. HE staining was used to observe the pathomorphological changes of lung tissue.

Results

2

Compared to those assessed at the same timepoint of the blank group， the weight of the model group at 24 h and 96 h significantly decreased （

P

＜0.05 or

P

＜0.01）； the structure of lung tissue was obviously destroyed from the pathological results； the levels of WBC， NEU， and LYN were increased （

P

＜0.01）； the levels of IL-6， IL-1β， TNF-α in the serum， alveolar lavage fluid and lung tissues， and the MPO level in the lung tissue significantly increased （

P

＜0.01）； the RL and Re levels increased， while Cydn， PEF and MVV levels decreased （

P

＜0.05 or

P

＜0.01）. Compared to those assessed at the same timepoint of the model group， there were no significant differences among groups in the body weight （

P

＞0.05）； the lung tissue injuries of the ceftriaxone sodium group and the QLF groups significantly improved from pathological results， especially in the OLF high-dose group； the WBC， NEU and LYM levels of QLF low and medium dose groups and the ceftriaxone sodium group were all significantly decreased （

P

＜0.05 or

P

＜0.01）； the IL-6， IL-1β， and TNF-α levels of the ceftriaxone sodium group and the QLF groups decreased significantly （

P

＜0.01）； regarding the lung function indicators， the RL and Re level of QLF high-dose group significantly decreased， while the Cdyn level， PEF and MVV level increased （

P

＜0.01）. When compared between different dose groups of QLF， the RL and Re levels， and the IL-6 and TNF-α levels of lung tissue were the lowest， while the Cydn， PEF and MVV levels were the highest， showing dose-dependent relation（

P

＜0.05 or

P

＜0.01）.

Conclusion

2

QLF can alleviate the pathological changes of lung tissues and improve the lung function in mice model with acute lung injury， and the high dose of QLF works best. The possible mechanism may be related to the inhibition of secretion of inflammatory factors in the body.