Effects and mechanism of Curcumin solid lipid nanoparticles loaded with flower-shaped lactose for inhalation on pulmonary inflammation in COPD model mice / 中国药房

ABSTRACT

OBJECTIVE To investigate the effects and mechanism of curcumin （Cur） solid lipid nanoparticles （SLN） loaded with flower-shaped lactose （Cur-SLN-FL） for lung inhalation on lung inflammation in chronic obstructive pulmonary disease （COPD） model mice. METHODS Firstly， the irritation of Cur-SLN-FL to lung tissue was investigated， and the local safety of inhalation materials was determined. Then， 10 mice were randomly selected and injected with normal saline through the trachea， and the other 50 mice were all injected with porcine trypsin solution （concentration of 33.3 mg/mL， dosage of 1.0 mL/kg） to induce the COPD model. After normal feeding for 28 days， the mice were divided into sham operation group， model group， budesonide group （20 mg/kg）， Cur-SLN-FL high-dose and low-dose groups （100， 50 mg/kg）， with 10 mice in each group. The corresponding drugs were given to each group， once a day， for 14 consecutive days. Twenty-four hours after the last administration， the bronchoalveolar lavage fluid （BALF） of mice in each group was collected and the differential count of white blood cells was determined. Hematoxylin-eosin （HE） staining was used to observe the histopathology of the trachea and lung tissue in each group. Masson staining was used to detect collagen deposition in the lung tissue of mice in each group. Immunohistochemical method was used to detect the positive expressions of nucleotide-binding oligomerization domains-like receptor protein-3 （NLRP3）， caspase-1 and interleukin-1β （IL-1β） in lung tissue of mice. Western blot assay was used to detect the protein expressions of NLRP3， caspase-1 and nuclear factor of kappa B（NF-κB） in lung tissue. RESULTS Cur-SLN-FL had no obvious pulmonary irritation. Compared with the sham operation group， the total number of white blood cells， neutrophils and eosinophils in BALF of the model group increased significantly， while the number of lymphocytes decreased significantly （P＜0.05）； ciliated columnar epithelium proliferated， thickened and exfoliated in the trachea， mucus accumulated in the cavity and interstitial inflammatory cells infiltrated in the lung tissue；the deposition of collagen fibers in lung tissue increased significantly， the positive expressions of NLRP3， caspase-1 and IL-1β in lung tissue increased significantly， and the expressions of NLRP3， caspase-1 and NF-κB protein in lung tissue all increased significantly （P＜0.05）. After giving Cur-SLN-FL， the above indexes were all improved to certain extent. CONCLUSIONS Cur-SLN-FL can improve the pulmonary inflammatory reaction in COPD model mice，and its mechanism may be through regulating the NLRP3 signaling pathway， inhibiting the expressions of caspase-1， NF-κB and IL-1β， thus alleviating the process of pulmonary fibrosis in COPD model mice.