花形乳糖装载姜黄素固体脂质纳米粒吸入微粉对COPD模型小鼠肺部炎症的影响及机制  

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

作　　者：李楠[1] 李旭[1] 王梓[1] 杨萍[1] 孔令钰[1] LI Nan;LI Xu;WANG Zi;YANG Ping;KONG Lingyu(Tianjin Institute of Pharmaceutical Science,Tianjin 300020,China)

机构地区：[1]天津市医药科学研究所,天津300020

出　　处：《中国药房》2023年第14期1691-1696,共6页China Pharmacy

基　　金：国家自然科学基金资助项目(No.81903565);天津市科技计划项目(No.21JCYBJC01630);天津市卫生健康科技项目(No.TJWJ2021MS046,No.TJWJ2021QN078)。

摘　　要：目的探讨肺吸入花形乳糖(FL)装载姜黄素(Cur)固体脂质纳米粒(SLN)吸入微粉(Cur-SLN-FL)对慢性阻塞性肺疾病(COPD)模型小鼠肺部炎症的影响及机制。方法对Cur-SLN-FL的肺部刺激性进行考察,明确吸入材料的局部安全性。然后随机选用10只小鼠经气管注入生理盐水,其余50只小鼠均滴注猪胰蛋白酶溶液(浓度为33.3 mg/mL、给药剂量为1.0 mL/kg)复制COPD模型,小鼠正常喂养28 d后分为假手术组、模型组、布地奈德组(20 mg/kg)和Cur-SLN-FL高、低剂量(100、50 mg/kg)组,每组10只。按要求给予相应药物,每日1次,连续14 d。末次给药24 h后,采集各组小鼠支气管肺泡灌洗液(BALF)并对其中的白细胞分类计数;采用苏木素-伊红(HE)染色观察气管和肺组织病理形态;采用Masson染色检测肺组织胶原纤维沉积;采用免疫组织化学法检测肺组织中核苷酸结合寡聚化结构域样受体蛋白3(NLRP3)、胱天蛋白酶1(caspase-1)、白细胞介素1β(IL-1β)的阳性表达;采用Western blot法检测肺组织中NLRP3、caspase-1、核因子κB(NF-κB)的蛋白表达。结果Cur-SLN-FL无明显肺部刺激性。与假手术组比较,模型组小鼠BALF中白细胞总数、中性粒细胞、嗜酸性粒细胞均显著增加,淋巴细胞数显著降低(P<0.05);气管见纤毛柱状上皮增生增厚、脱落,腔内可见黏液蓄积,肺组织可见间质炎性细胞浸润;肺组织胶原纤维沉积明显增加,肺组织中NLRP3、caspase-1、IL-1β的阳性表达明显增强,肺组织中NLRP3、caspase-1、NF-κB蛋白的表达水平均显著升高(P<0.05)。给予Cur-SLN-FL后,上述各指标均有一定程度改善。结论Cur-SLN-FL能够改善COPD模型小鼠的肺部炎症反应,其机制可能是通过调控NLRP3信号通路,抑制caspase-1、NF-κB、IL-1β的表达,进而缓解小鼠肺组织纤维化的进程。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

关 键 词：花形乳糖 姜黄素固体脂质纳米粒 吸入微粉 肺部刺激性 慢性阻塞性肺疾病 NLRP3炎症小体 

分 类 号：R943[医药卫生—药剂学]