小檗碱经HIF-1α/PDHK1通路调控糖酵解改善哮喘的作用及机制 点击下载
| 论文标题： | 小檗碱经HIF-1α/PDHK1通路调控糖酵解改善哮喘的作用及机制 |
| 英文标题： | |
| 中文摘要： | 目的 探讨小檗碱经缺氧诱导因子1α（HIF-1α）/丙酮酸脱氢酶激酶1（PDHK1）通路调控糖酵解改善哮喘小鼠的作用及机制。方法将小鼠随机分为空白对照组，模型组，小檗碱低、高剂量组（100、200mg/kg，灌胃），二甲基草酰甘氨酸（DMOG，HIF-1α激动剂）组（2mg，鼻腔滴注），小檗碱+DMOG组（灌胃200mg/kg小檗碱+鼻腔滴注2mgDMOG），每组12只。除空白对照组外，其余各组小鼠均采用卵清蛋白致敏与激发法建立哮喘模型。在激发期，给予小鼠相应药物或生理盐水，每天1次，连续6d。末次激发24h后，检测小鼠肺功能和气道反应性；检测血清中卵清蛋白特异性免疫球蛋白E（OVA-sIgE）含量；计数支气管肺泡灌洗液（BALF）中炎症细胞数量；观察支气管炎症和杯状细胞增生情况；检测肺组织中炎症因子[白细胞介素4（IL-4）、IL-5、IL-13]水平、糖酵解产物[乳酸、丙酮酸、三磷酸腺苷]含量以及HIF-1α/PDHK1通路相关mRNA及蛋白表达。结果与模型组比较，小檗碱低、高剂量组小鼠动态肺顺应性、呼气峰值流速、用力肺活量（FVC）、0.1秒用力呼气容积（FEV0.1）、FEV0.1/FVC均显著升高或增大（P＜0.05），气道阻力、增强呼气间歇值均显著减小或降低（P＜0.05）；血清中OVA-sIgE含量，BALF中白细胞、中性粒细胞、淋巴细胞、单核细胞、嗜酸性粒细胞和嗜碱性粒细胞数量，支气管炎症评分和杯状细胞增生评分，肺组织中炎症因子水平、糖酵解产物含量和HIF-1α、PDHK1、M2型丙酮酸激酶、乳酸脱氢酶A的mRNA及蛋白表达水平均显著降低（P＜0.05）。DMOG可显著逆转高剂量小檗碱对哮喘小鼠的改善作用（P＜0.05）。结论小檗碱可通过抑制HIF-1α/PDHK1通路，降低糖酵解水平，从而改善哮喘小鼠的气道炎症和气道高反应性。 |
| 英文摘要： | OBJECTIVE To explore the effect and mechanism of berberine in ameliorating asthma in mice by regulating glycolysis via the hypoxia inducible factor-1α （HIF-1α）/pyruvate dehydrogenase kinase-1 （PDHK1） pathway.METHODS Mice were randomly divided into blank control group， model group， low- and high-dose berberine groups （100， 200 mg/kg， intragastric administration）， dimethyloxalylglycine （DMOG， HIF-1α agonist） group （2 mg， intranasal instillation）， and berberine+DMOG group （intragastric administration of 200 mg/kg berberine plus intranasal instillation of 2 mg DMOG）， with 12 mice in each group. Except for the blank control group， mice in the remaining groups were subjected to ovalbumin-induced sensitization and challenge to establish the asthma model. During the challenge period， mice were given corresponding drugs or normal saline once a day for 6 consecutive days. At 24 h after the last challenge， pulmonary function and airway reactivity of mice were determined； the content of ovalbumin-specific immunoglobulin E （OVA-sIgE） in serum was detected； inflammatory cells in bronchoalveolar lavage fluid （BALF） were counted； bronchial inflammation and goblet cell hyperplasia were histologically evaluated； the levels of inflammatory cytokines [interleukin-4 （IL-4）， IL-5， IL-13]， contents of glycolytic products [lactic acid， pyruvic acid， adenosine triphosphate （ATP）]， as well as mRNA and protein expressions related to the HIF-1α/PDHK1 pathway in lung tissue were measured.RESULTS Compared with the model group， the low- and high-dose berberine groups exhibited significantly elevated or increased dynamic lung compliance， peak expiratory flow， forced vital capacity （FVC）， forced expiratory volume in 0.1 second （FEV 0.1 ）， and FEV 0.1 /FVC （ P ＜0.05）， accompanied by significantly decreased airway resistance and enhanced pause value （ P ＜0.05）. Moreover， serum OVA-sIgE content， counts of white blood cell， neutrophil， lymphocyte， monocyte， eosinophil and basophil in BALF， scores for bronchial inflammation and goblet cell hyperplasia， levels of pulmonary inflammatory cytokines and contents of glycolytic products， as well as mRNA and protein expressions of HIF-1α， PDHK1， pyruvate kinase M2 and lactate dehydrogenase A were all significantly reduced （ P ＜0.05）. DMOG pretreatment obviously reversed the protective effects of high-dose berberine in asthmatic mice （ P ＜0.05）.CONCLUSIONS Berberine can inhibit the HIF-1α/PDHK1 pathway to decrease glycolytic level， so as to ameliorate airway inflammation and airway hyperresponsiveness in asthmatic mice. |
| 期刊： | 2026年第37卷第17期 |
| 作者： | 姜宇芬；任志红；高山；胡新业 |
| 英文作者： | JIANG Yufen，REN Zhihong，GAO Shan，HU Xinye |
| 关键字： | 小檗碱；哮喘；气道炎症；气道高反应性；HIF-1α/PDHK1通路；糖酵解 |
| KEYWORDS： | asthma;airway inflammation;airway hyperresponsiveness;HIF-1α/PDHK1 pathway;glycolysis |
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