摘要
目的探究藏红花素(crocin)对慢性阻塞性肺疾病(chronic obstructive pulmonary disease,COPD)大鼠炎症反应及肺损伤的作用情况及其机制。方法 60只SD大鼠随机分为空白对照组、COPD组、COPD+低剂量藏红花素组(10 mg/kg)、COPD+高剂量藏红花素组(50 mg/kg),采用香烟烟熏联合气道内注入脂多糖的方法构建大鼠COPD模型。30 d后采用肺功能检测仪检测大鼠相关肺功能指标,HE染色观察大鼠肺组织病理形态变化,ELISA法检测血清与肺泡灌洗液(BALF)中白细胞介素(IL)-1β、白细胞介素(IL)-6与肿瘤坏死因子(TNF)-α的含量,TUNEL染色检测肺组织中肺泡上皮细胞凋亡情况,qRT-PCR与Western blot检测肺组织中过氧化物酶体增殖物受体γ共激活因子1α(PGC-1α)、去乙酰化酶3(SIRT3)在mRNA与蛋白水平上的表达。结果与空白对照组比较,COPD组大鼠肺组织中肺泡结构破坏,出现大量炎性细胞浸润,肺功能指标PEF、PIF、FEV0.3/FVC以及肺组织中PGC-1α、SIRT3 mRNA与蛋白表达量均下降,血清和BALF中IL-1β、IL-6、TNF-α含量及肺泡上皮细胞凋亡率均升高(P<0.01)。与COPD组比较,高、低剂量藏红花素干预后,大鼠肺组织病变情况明显改善,肺功能指标PEF、PIF、FEV0.3/FVC及肺组织中PGC-1α、SIRT3 mRNA与PGC-1α蛋白表达量均升高,血清和BALF中IL-1β、IL-6、TNF-α含量与肺泡上皮细胞凋亡率均下降(P<0.01)。与COPD+低剂量藏红花素组比较,COPD+高剂量藏红花素组大鼠肺组织病变改善更明显,肺功能指标PEF、PIF、FEV0.3/FVC及肺组织中PGC-1α、SIRT3 mRNA与PGC-1α蛋白表达量均升高,血清和BALF中IL-1β、IL-6、TNF-α含量与肺泡上皮细胞凋亡率均下降(P<0.01)。结论藏红花素对COPD大鼠肺损伤具有一定的保护作用,其机制可能与抑制炎症反应及肺泡上皮细胞凋亡,提高PGC-1α、SIRT3表达有关。
Objective To investigate the effect and mechanism of crocin on inflammatory response and lung injury in chronic obstructive pulmonary disease(COPD)rats.Methods 60 SD rats were randomly divided into the blank control group,the COPD group,the COPD+low-dose crocin group(10 mg/kg),and the COPD+high-dose crocin group(50 mg/kg).It used cigarette smoking combined with airway lipopolysaccharide injection to construct COPD model in rats.30 days later,lung function indicators of rats were detected by the pulmonary function tester.HE staining was used to observe the pathological changes of lung tissue in rats,The levels of IL-1β,IL-6 and tumor necrosis factor(TNF-α)in serum and alveolar lavage fluid(BALF)were detected by ELISA.It used TUNEL staining to detect the apoptosis of alveolar cells in lung tissue,qRT-PCR and Western blot to detect the expression levels of peroxisome proliferator receptor gamma coactivator 1α(PGC-1α)and Sirtuin-3(SIRT3)in lung tissues.Results Compared with the blank control group,the alveolar structure in lung tissue of the COPD group was damaged,and a large number of inflammatory cells infiltrated,pulmonary function indicators PEF,PIF,FEV0.3/FVC and theexpression of PGC-1α,SIRT3 mRNA and protein in lung tissues decreased,the levels of IL-1β,IL-6,TNF-αand the number of alveolar apoptosis in serum and BALF were increased(P<0.01).Compared with the COPD group,the lung tissue lesions in rats were significantly improved after high and low dose crocin intervention,pulmonary function indicators PEF,PIF,FEV0.3/FVC and PGC-1α,SIRT3 mRNA and PGC-1αprotein expression in lung tissues were increased.The levels of IL-1β,IL-6,TNF-αand the number of alveolar apoptosis in serum and BALF were decreased(P<0.01).Compared with the COPD+low-dose crocin group,the COPD+high-dose crocin group showed more significant improvement in lung tissue lesions.Pulmonary function indicators PEF,PIF,FEV0.3/FVC and PGC-1α,SIRT3 mRNA and PGC-1αprotein expression in lung tissues were increased,and the levels of IL-1β,IL-6,TNF-αand the number of alveolar apoptosis in serum and BALF were decreased(P<0.01).Conclusion Crocin has a certain protective effect on lung injury in COPD rats,and its mechanism may be related to inhibiting the inflammatory response and alveolar epithelial cell apoptosis and increasing the expression of PGC-1αand SIRT3.
作者
谢圆媛
杨丹芬
王莉
XIE Yuan-yuan;YANG Dan-fen;WANG Li(Department of Geriatrics,the Affiliated Hospital of Yan′an University,Yan'an,Shaanxi 716000,China)
出处
《临床肺科杂志》
2020年第11期1648-1654,共7页
Journal of Clinical Pulmonary Medicine
基金
陕西省科技计划项目(No.2019ZP07258)。
作者简介
通信作者:杨丹芬,E-mail:foreme@163.com。
