姜黄素对慢性阻塞性肺疾病大鼠肺泡上皮细胞内质网应激的影响

Effect of curcumin on endoplasmic reticulum stress of alveolar epithelial cells in a rat model of chronic obstructive pulmonary disease

目的探索姜黄素对慢性阻塞性肺疾病(chronic obstructive pulmonary disease,COPD)大鼠肺泡上皮细胞内质网应激的调节作用。方法雄性SD大鼠随机分为正常对照组、COPD模型组、姜黄素干预组和溶剂对照组,采用香烟烟熏联合气管内注射脂多糖的方法建立COPD大鼠模型,并按照分组情况对大鼠进行干预。干预结束后计数支气管肺泡灌洗液(bronchoalveolar lavage fluid,BALF)中的细胞总数、中性粒细胞和巨噬细胞数量,HE染色观察肺组织病理学改变,透射电子显微镜观察肺泡上皮细胞内质网形态,免疫组织化学法检测葡萄糖调节蛋白78(glucose-regulated protein 78,GRP78)在肺泡上皮细胞中的表达水平。结果与正常对照组比较,COPD模型组大鼠BALF中细胞总数、中性粒细胞和巨噬细胞数量均显著升高(P<0.05);姜黄素干预组大鼠BALF中细胞总数、中性粒细胞和巨噬细胞数量较COPD模型组降低(P<0.05)。光镜和透射电子显微镜观察显示COPD模型组大鼠肺泡腔扩张、肺泡上皮细胞内质网肿胀,姜黄素干预可减轻肺泡上皮细胞及内质网损伤。与正常对照组相比,GRP78在COPD大鼠肺泡上皮细胞中表达水平显著升高(P<0.05);姜黄素干预可显著下调GRP78在COPD大鼠肺泡上皮细胞中表达水平(P<0.05)。结论姜黄素可能通过抑制肺泡上皮细胞内质网应激而发挥对COPD的保护作用。

Objective To explore the effect of curcumin on endoplasmic reticulum stress of alveolar epithelial cells in a rat model of chronic obstructive pulmonary disease(COPD).Methods Male SD rats were randomly divided into normal control,COPD model,curcumin-treated and solvent control groups.The rat model of COPD was induced by cigarette smoke exposure combined with intratracheal administration of lipopolysaccharide,and rats were further treated according to different groups.The numbers of total cells,neutrophils and macrophages in bronchoalveolar lavage fluid(BALF)were counted.Pathological changes of lung tissues were studied by HE staining.The endoplasmic reticulum morphology of alveolar epithelial cells was observed using transmission electron microscopy.The protein expression of glucose-regulated protein 78(GRP78)in alveolar epithelial cells was detected by immunohistochemistry.Results Compared with those in normal control group,the numbers of total cells,neutrophils and macrophages in BALF from rats in COPD model group were all significantly increased(P<0.05).The numbers of total cells,neutrophils and macrophages in BALF from rats in curcumin-treated group were significantly lower than those in COPD model group(P<0.05).Light microscopy and transmission electron microscopy showed enlarged alveolar space and swollen endoplasmic reticulum of alveolar epithelial cells in rats from COPD model group.The damage of alveolar epithelial cells and endoplasmic reticulum in COPD rats was attenuated by curcumin treatment.Compared with that in normal control group,the expression of GRP78 in alveolar epithelial cells in rats from COPD model group was significantly increased(P<0.05).And the protein expression level of GRP78 in alveolar epithelial cells in COPD rats was significantly down-regulated by curcumin treatment(P<0.05).Conclusion Curcumin plays a protective effect against COPD possibly by inhibiting endoplasmic reticulum stress of alveolar epithelial cells.