| 261 | 0 | 100 |
| 下载次数 | 被引频次 | 阅读次数 |
目的 探究衢枳壳总黄酮（TFQA）对肥胖型哮喘模型小鼠肺损伤的改善作用及脂质代谢的影响，并探讨其药理作用。方法 采用高脂饲料（脂肪比例为60%）饲养结合卵清蛋白（OVA）致敏建立肥胖型哮喘模型小鼠。实验设立健康对照组、肥胖对照组、肥胖型哮喘组和TFQA干预组，各8只雄性BALB/c小鼠。测定小鼠的肺功能指标及支气管肺泡灌洗液（BALF）中白细胞数量，血清IL-1β、IL-17A、IL-6、IL-10、瘦素（LEP）、脂联素（ADPN）和游离脂肪酸（FFA）水平（ELISA法），以及肝组织脂质相关蛋白表达水平（Western blot法）。观察肝、肺组织的病理变化（HE染色）及肝脂肪的堆积情况（油红O染色）。结果 与健康对照组相比，肥胖型哮喘组小鼠气道阻力（RI）和功能残气量（FRC）值增加（P<0.01）；肺功能下降，血清LEP和FFA水平增加，IL-10和ADPN水平减少；HE染色结果显示，肝肺组织损伤严重，可见许多白色空泡，肝索紊乱；肝组织脂肪堆积增加，固醇调节元件结合蛋白-1c(SREBP-1c)、CCAAT/增强子结合蛋白β(C-EBP β)和脂肪酸合成酶（FAS）表达上调（P<0.01）；过氧化物酶体增殖物激活受体-α(PPAR-α)表达下调（P<0.01）。与肥胖型哮喘组相比，TFQA干预组小鼠以上效应均有所改善，同时小鼠肝组织中红色脂肪滴减少，肝组织中肉碱棕榈酰转移酶-1(CPT-1)、CPT-2、甘油三酯脂肪酶（TGL）、激素敏感性脂肪酶（HSL）/P-HSL、PPAR-α蛋白水平增加（P<0.01）。结论 TFQA能改善肥胖型哮喘模型小鼠的肺功能，改善肺损伤，其作用机制可能与抑制炎症反应和调节脂质代谢相关。
Abstract：AIM To explore the effect of total flavonoids from Quzhou Aurantii Fructus(TFQA) on lung injury and lipid metabolism in obese asthmatic mice and its pharmacological effects. METHODS Obese asthmatic mice sensitized with ovalbumin(OVA) were fed a high-fat diet(60% fat ratio). The experiment included a healthy control group, an obese control group, an obese asthma group, and a TFQA intervention group, with 8 male BALB/c mice in each group. The lung function indices of mice were detected. Leukocytes in broncho alveolar lavage fluid were determined by the cell classification counting method. Serum levels of interleukin-1β(IL-1β), interleukin-17A(IL-17A), interleukin-6(IL-6), interleukin-10(IL-10), leptin(LEP), adiponectin(ADPN), and free fatty acid(FFA) were determined by ELISA. Western blot assay was employed to test lipid-associated protein expression in liver tissues. Pathological changes in liver and lung tissues were observed using hematoxylin-eosin(HE) staining, while lipid accumulation in liver tissues was assessed via Oil Red O staining. RESULTS Compared with the healthy control group, the airway resistance(RI) and functional residual capacity(FRC) of the obese asthma mice increased, with statistically significant differences(P < 0.01). Pulmonary function had declined. Serum LEP and FFA levels increased, IL-10 and ADPN levels decreased, HE staining showed that the liver and lung tissue were seriously damaged, with many white vacuoles and hepatic cord disorders. Liver tissue fat accumulation increased, sterol regulatory element-binding protein-1c(SREBP-1c), CCAAT enhancer binding protein beta(C-EBP β) and fatty acid synthase(FAS) were up-regulated, with statistically significant differences(P < 0.01). The expression of peroxisome proliferator-activated receptor-α(PPAR-α) was downregulated, and the difference was statistically significant(P < 0.01). Compared with the obese asthma model group, the above effects of TFQA were improved after intervention in obese asthmatic mice. At the same time red fat droplets in mouse liver tissue were reduced, and liver tissue contained carnitine palmitoyltransferase-1(CPT-1), carnitine palmitoyltransferase-1(CPT-2), protein levels of triglyceride lipase(TGL), hormone sensitive lipase(HSL)/P-HSL and PPAR-α were increased, with statistically significant differences(P < 0.01). CONCLUSION TFQA improved lung function in obesity-asthma mice, with its mechanism possibly related to inflammatory response inhibition and regulation of lipid metabolism.
[1]王海涛,唐华平.胰岛素样生长因子-1对肥胖型哮喘小鼠的作用[J].青岛大学学报(医学版), 2020, 56(5):597.
[2] PETERS U, DIXON A E, FORNO E. Obesity and asthma[J]. J Allergy Clin Immunol, 2018, 141(4):1169.
[3] CHEN K, SHEN Z W, GU W J, et al. Prevalence of obesity and associated complications in China:a cross-sectional, real-world study in 15.8 million adults[J]. Diabetes Obes Metab, 2023,25(11):3390.
[4] PEERBOOM S, GRAFF S, SEIDEL L, et al. Predictors of a good response to inhaled corticosteroids in obesity-associated asthma[J].Biochem Pharmacol, 2020, 179:113994.
[5] ZHANG L J, LIANG D X, LIU L L, et al. Plumbagin alleviates obesity-related asthma:targeting inflammation, oxidative stress,and the AMPK pathway[J]. Immun Inflamm Dis, 2023, 11(9):e1025.
[6] SIM S, CHOI Y, PARK H S. Potential metabolic biomarkers in adult asthmatics[J]. Metabolites, 2021, 11(7):430.
[7] SáNCHEZ-ORTEGAH, JIMéNEZ-CORTEGANAC,NOVALBOS-RUIZ J P, et al. Role of leptin as a link between asthma and obesity:a systematic review and meta-analysis[J].Int J Mol Sci, 2022, 24(1):546.
[8] MIZUTA K, MATOBA A, SHIBATA S, et al. Obesity-induced asthma:role of free fatty acid receptors[J]. Jpn Dent Sci Rev,2019, 55(1):103.
[9]浙江省食品药品监督管理局.浙江省中药炮制规范[M]. 2015年版.北京:中国医药科技出版社, 2016:181-182.
[10] GAO L, ZHANG H, YUAN C H, et al. Citrus aurantium'Changshan-Huyou'-an ethnopharmacological and phytochemical review[J]. Front Pharmacol, 2022, 13:983470.
[11] WANG J P, LI T, CAI H Y, et al. Protective effects of total flavonoids from QuZhi Qiao(fruit of Citrusparadisicv.Changshanhuyou)on OVA-induced allergic airway inflammation and remodeling through MAPKs and Smad2/3 signaling pathway[J]. Biomed Pharmacother, 2021, 138:111421.
[12] LING Y, SHI Z, YANG X L, et al. Hypolipidemic effect of pure total flavonoids from peel of Citrus(PTFC)on hamsters of hyperlipidemia and its potential mechanism[J]. Exp Gerontol,2020, 130:110786.
[13]刘小娟,姜小琴,方月娟,等.衢枳壳总黄酮通过NF-κB信号通路对RSV感染哮喘小鼠肺损伤的保护作用[J].中华医院感染学杂志, 2021, 31(22):3376.
[14] LIU F, SUN Y, ZHOU Y, et al. ORMDL3-mediated bronchial epithelial pyroptosis leads to lung inflammation in obese mice with asthma[J]. Mol Med Rep, 2023, 28(4):186.
[15] MA Z F, LI C, XUE L N, et al. Linggan Wuwei Jiangxin formula ameliorates airway hyperresponsiveness through suppression of IL-1β and IL-17A expression in allergic asthmatic mice especially with diet-induced obesity[J]. Ann Transl Med, 2021, 9(8):682.
[16]王思为,蓝天,郑芳,等.衢枳壳提取物对CCl4诱导的肝纤维化小鼠肝脏炎症及NF-κB/NLRP3炎性体通路的影响[J].中国中药杂志, 2021, 46(6):1474.
[17] HUDLER A C, DíAZ I R R, SHARMA S, et al. Gaps and future directions in clinical research on obesity-related asthma[J].Pulm Ther, 2023, 9(3):309.
[18] SUN C B, LI A, WANG H, et al. Positive regulation of acetate in adipocyte differentiation and lipid deposition in obese mice[J].Nutrients, 2023, 15(17):3736.
[19] BANTULàM, TUBITA V, ROCA-FERRER J, et al. Differences in inflammatory cytokine profile in obesity-associated asthma:effects of weight loss[J]. J Clin Med, 2022, 11(13):3782.
[20] YING X L, LIN J, YUAN S H, et al. Comparison of pulmonary function and inflammation in children/adolescents with new-onset asthma with different adiposity statuses[J]. Nutrients, 2022,14(14):2968.
[21] LEE K D, ILAVENIL S, KARNAN M, et al. Novel Bacillus ginsengihumi CMRO6 inhibits adipogenesis via p38MAPK/Erk44/42 and stimulates glucose uptake in 3T3-L1 pre-adipocytes through Akt/AS160 signaling[J]. Int J Mol Sci, 2022, 23(9):4727.
[22]叶爱琴,蒋剑平,李润,等.衢枳壳黄酮对高脂血症金黄地鼠降血脂作用及其机制研究[J].中国现代应用药学, 2020, 37(16):1938.
[23]魏水清,程慧雯,郝月琴,等. TREM-1抑制剂对肥胖哮喘小鼠气道炎症的影响[J].青岛大学学报(医学版), 2022, 58(5):739.
基本信息:
DOI：10.19577/j.1007-4406.2025.06.003
中图分类号:R285.5;R-332
引用信息:
[1]刘小娟,方月娟,梅国花.衢枳壳总黄酮对肥胖型哮喘模型小鼠肺损伤的改善作用及脂质代谢的影响[J].中国临床药学杂志,2025,34(06):414-421.DOI:10.19577/j.1007-4406.2025.06.003.
基金信息:
衢州市重点科技攻关项目（编号2022K79）
2025-06-25
2025-06-25