薏苡仁提取物豆甾醇通过PPARγ-代谢重编程-M2极化轴改善慢性阻塞性肺疾病肺损伤OA
Stigmasterol extracted from Coix lacryma-jobi ameliorates COPD lung injury via PPARγ-metabolic reprogramming-M2 polarization axis
目的 探究薏苡仁提取物豆甾醇治疗慢性阻塞性肺疾病(chronic obstructive pulmonary disease,COPD)模型大鼠的作用机制.方法 40只健康雄性SD大鼠[体质量(120±10)g],采用随机数字表法分为4组(n=10):空白(NC)组、模型(Mock)组、豆甾醇(Stigmasterol)组(豆甾醇20 mg/kg)及豆甾醇+GW9662(Stigmasterol+GW9662)组[豆甾醇 20 mg/kg+过氧化物酶体增殖物激活受体γ(peroxisome proliferator-activated receptor γ,PPARγ)拮抗剂GW9662(1 mg/kg)].采用烟熏联合气管内滴注脂多糖(lipopolysaccharide,LPS,1 mg/kg)的方法建立COPD大鼠模型,连续干预14 d后,分离肺泡巨噬细胞,采用流式细胞术分析M1/M2极化;qRT-PCR、Western blot及ELISA检测PPARγ表达;采用Seahorse XF细胞能量代谢分析系统检测巨噬细胞的耗氧率(oxygen consumption rate,OCR)与细胞外酸化率(extracellular acidification rate,ECAR);HE染色及免疫组化观察肺组织病理与巨噬细胞浸润.结果与NC组相比,Mock组M1/M2比率显著升高(P<0.01),PPARγ的mRNA及蛋白表达水平均显著降低(P<0.001),同时肺泡巨噬细胞的线粒体基础OCR、最大OCR及糖酵解ECAR亦显著降低(P<0.01),肺组织出现典型的肺泡结构破坏、炎性细胞浸润等病理损伤.与Mock组相比,豆甾醇干预能显著逆转上述异常:降低M1/M2比率(P<0.01),上调PPARγ表达(P<0.01),改善线粒体呼吸与糖酵解代谢能力,并减轻肺组织病理损伤(P<0.05).然而,联合使用PPARγ拮抗剂GW9662后,豆甾醇对M2极化的促进作用、对PPARγ表达的上调作用、对细胞代谢重编程(OCR与ECAR)的改善作用以及对肺组织损伤的保护作用均被显著削弱.结论 薏苡仁提取物豆甾醇通过激活PPARγ、促进肺泡巨噬细胞代谢重编程并向M2型极化,从而改善COPD大鼠肺组织损伤.
Objective To investigate the mechanism of stigmasterol,an extract from Coicis Semen,in treating rats with a chronic obstructive pulmonary disease(COPD)model.Methods Forty healthy male SD rats(body weight:120±10 g)were randomly divided into four groups(n=10)using a random number table:blank control(NC)group,model(Mock)group,Stigmasterol group(stigmasterol 20 mg/kg),and stigmasterol+GW9662 group(stigmasterol 20 mg/kg+peroxisome proliferator-activated receptor γ(PPARγ)antagonist GW9662 1 mg/kg).The COPD rat model was established by smoke exposure combined with intratracheal instillation of lipopolysaccharide(LPS,1 mg/kg).After 14 d of intervention,alveolar macrophages were isolated.M1/M2 polarization was analyzed by flow cytometry;PPARγ expression was detected using qRT-PCR,Western blot,and ELISA;macrophage oxygen consumption rate(OCR)and extracellular acidification rate(ECAR)were measured with a Seahorse XF Analyzer;and lung tissue pathology and macrophage infiltration were observed via HE staining and immunohistochemistry.Results Compared with the NC group,the Mock group exhibited a significantly increased M1/M2 ratio(P<0.01),markedly reduced PPARγ expression at both mRNA and protein levels(P<0.001),and decreased mitochondrial basal OCR,maximal OCR,and glycolytic ECAR in alveolar macrophages(P<0.01).Lung tissues showed typical histopathological damage,including alveolar destruction and inflammatory cell infiltration.Stigmasterol intervention reversed these abnormalities by decreasing the M1/M2 ratio(P<0.01),upregulating PPARγ expression(P<0.01),improving mitochondrial respiration and glycolytic capacity(as indicated by OCR and ECAR),and alleviating lung tissue histopathological damage(P<0.05).However,co-administration of the PPARγ antagonist GW9662 significantly attenuated stigmasterol's beneficial effects on promoting M2 macrophage polarization,upregulating PPARγ expression,improving cellular metabolic reprogramming(OCR and ECAR),and protecting against lung tissue damage.Conclusion Stigmasterol from Coicis Semen ameliorates lung injury in COPD rats by activating PPARγ,which reprograms alveolar macrophage metabolism and drives M2 polarization.
常星;程向红;曹亮
陕西理工大学附属医院普通内科,陕西汉中陕西理工大学附属医院普通内科,陕西汉中西安交通大学第一附属医院榆林医院药剂科,陕西榆林
医药卫生
豆甾醇过氧化物酶体增殖物激活受体γ慢性阻塞性肺疾病肺泡巨噬细胞
stigmasterolperoxisome proliferator-activated receptor γchronic obstructive pulmonary diseasealveolar macrophage
《陆军军医大学学报》 2026 (3)
317-324,8
陕西省重点研发计划(2022SF-346) Supported by the Key Research and Development Program of Shaanxi Province(2022SF-346).
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