[1]常玉平,谢琪,周腾腾,等.橙皮苷调节IL-6/JAK2/STAT3信号通路对大鼠肥胖症模型的降脂作用实验研究[J].陕西医学杂志,2025,54(6):759-764.[doi:DOI:10.3969/j.issn.1000-7377.2025.06.007]
 CHANG Yuping,XIE Qi,ZHOU Tengteng,et al.Lipid-lowering effect of hesperidin on obesity in rats by regulating IL-6/JAK2/STAT3 signaling pathway[J].,2025,54(6):759-764.[doi:DOI:10.3969/j.issn.1000-7377.2025.06.007]
点击复制

橙皮苷调节IL-6/JAK2/STAT3信号通路对大鼠肥胖症模型的降脂作用实验研究

《陕西医学杂志》[ISSN:1000-7377/CN:61-1281/TN]

卷:
54
期数:
2025年6期
页码:
759-764
栏目:
基础研究
出版日期:
2025-06-05

文章信息/Info

Title:
Lipid-lowering effect of hesperidin on obesity in rats by regulating IL-6/JAK2/STAT3 signaling pathway
作者:
常玉平1谢琪2周腾腾3赵晋4王莉娜5程玲玲1郭丹丹6
(1.邯郸市人民医院神经内科,河北 邯郸 056001;2.河北医科大学第四医院营养科,河北 石家庄 050010;3.河北医科大学第四医院肿瘤内科,河北 石家庄 050010;4.邯郸市人民医院中医科,河北 邯郸 056001;5.邯郸市人民医院妇产科,河北 邯郸 056001;6.邯郸市中心医院药学部,河北 邯郸 057150)
Author(s):
CHANG Yuping1XIE Qi2ZHOU Tengteng3ZHAO Jin4WANG Lina5CHENG Lingling1GUO Dandan6
(1.Department of Neurology,Handan People’s Hospital,Handan 056001,China;2.Department of Nutrition,the Fourth Hospital of Hebei Medical University,Shijiazhuang 050010,China;3.Department of Oncology,the Fourth Hospital of Hebei Medical University,Shijiazhuang 050010,China;4.Department of Traditional Chinese Medicine,Handan People’s Hospital,Handan 056001,China;5.Department of Obstetrics and Gynecology,Handan People’s Hospital,Handan 056001,China;6.Department of Pharmacy,Handan Central Hospital,Handan 057150,China)
关键词:
肥胖症橙皮苷白细胞介素-6Janus酪氨酸激酶2信号转导与转录因子3降脂作用信号通路大鼠
Keywords:
ObesityHesperidinInterleukin-6Janus tyrosine kinase 2Signal transducer and activator of transcription 3Lipid-lowering effectSignaling pathwayRats
分类号:
R 285
DOI:
DOI:10.3969/j.issn.1000-7377.2025.06.007
文献标志码:
A
摘要:
目的:探讨橙皮苷对大鼠肥胖症模型的降脂作用及机制。方法:通过高脂饲料喂养构建肥胖症大鼠模型,将造模成功大鼠随机分为模型组(Model组)、橙皮苷低剂量组(Hesperidin-L组)、橙皮苷高剂量组(Hesperidin-H组)和橙皮苷高剂量+Janus酪氨酸激酶2(JAK2)激活剂香豆素A1组(Hesperidin-H+CA1组),每组18只。另取18只大鼠给予普通饲料喂养,设为对照组(Control组)。给药结束后,称量各组大鼠体重并计算Lee’s指数和肥胖率;酶联免疫吸附试验(ELISA)检测血清总胆固醇(TC)、甘油三酯(TG)、高密度脂蛋白胆固醇(HDL-C)、低密度脂蛋白胆固醇(LDL-C)含量及炎症因子白细胞介素-1β(IL-1β)、IL-6、肿瘤坏死因子-α(TNF-α)水平;HE染色观察肝组织脂肪细胞病理变化;油红O染色检测肝组织脂肪堆积程度;Western blot检测磷酸化JAK2(p-JAK2)/JAK2、磷酸化信号转导与转录因子3(p-STAT3)/STAT3表达。结果:与Control组比较,Model组肝细胞结构紊乱,肝细胞肿胀,脂肪细胞肥大呈空泡状,细胞壁变薄,炎症细胞浸润明显,红色脂滴在肝脏中大面积弥漫,脂质沉积增多,体重、Lee’s指数、肥胖率以及TG、TC、LDL-C、IL-1β、IL-6、TNF-α、p-JAK2/JAK2、p-STAT3/STAT3水平升高,HDL-C水平降低(均P<0.05)。与Model组比较,Hesperidin-L和Hesperidin-H组肝细胞基本恢复正常,脂肪细胞变小,细胞壁厚度增加,炎症细胞浸润现象减少,红色脂滴呈小颗粒状且分布不规则,脂滴数量减少,体重、Lee’s指数、肥胖率以及TG、TC、LDL-C、IL-1β、IL-6、TNF-α、p-JAK2/JAK2、p-STAT3/STAT3水平降低,HDL-C水平升高,且Hesperidin-H组变化更明显(均P<0.05)。与Hesperidin-H组比较,Hesperidin-H+CA1组肝细胞肥大,脂肪变性明显,脂肪细胞呈空泡状,大量炎症细胞浸润,红色脂滴大量分布,脂质堆积明显,体重、Lee’s指数、肥胖率以及TG、TC、LDL-C、IL-1β、IL-6、TNF-α、p-JAK2/JAK2、p-STAT3/STAT3水平升高,HDL-C水平降低(均P<0.05)。结论:橙皮苷可对大鼠肥胖症模型发挥降脂作用,其机制与抑制IL-6/JAK2/STAT3信号通路有关。
Abstract:
Objective:To investigate the lipid-lowering effect of hesperidin on obesity in rats and its mechanism.Methods:The obese rat model was constructed by high-fat diet feeding,and the successfully modeled rats were randomly grouped into model group (Model group),hesperidin low-dose group (Hesperidin-L group) and high-dose group (hesperidin-H group),hesperidin high-dose+Janus tyrosine kinase 2 (JAK2) activator coumarin A1 group (Hesperidin-H+CA1 group),18 rats in each group.Another 18 rats were fed with normal diet and were set as Control group.At the end of the administration,rats were weighed,and the Lee’s Index and obesity rate were calculated;ELISA was used to detect the contents of TC,TG,HDL-C,LDL-C and inflammatory cytokines IL-1β,IL-6,TNF-α in serum;HE staining was used to observe the pathological changes of adipocytes in liver tissue;Oil red O staining was used to detect the degree of fat accumulation in liver tissue;Western blot was used to detect the expressions of p-JAK2/JAK2 and phosphorylated signal transducer and transcription factor 3 (p-STAT3)/STAT3.Results:Compared with the Control group,the Model group had hepatocyte structure disorder,hepatocytes were swollen,adipocytes were hypertrophied and vacuole-like,the cell wall was thinned,inflammatory cell infiltration was obvious,red lipid droplets diffused in the liver,and lipid deposition increased,the weight,Lee’s Index,obesity rate,and TG,TC,LDL-C,IL-1β,IL-6,TNF-α,p-JAK2/JAK2,p-STAT3/STAT3 levels were increased,the HDL-C level was decreased (all P<0.05).Compared with the Model group,the hepatocytes in the Hesperidin-L and Hesperidin-H groups basically returned to normal,the adipocytes became smaller,the thickness of the cell wall increased,the infiltration of inflammatory cells decreased,the red lipid droplets were small granular and irregularly distributed,and the number of lipid droplets decreased,the weight,Lee’s Index,obesity rate,and TG,TC,LDL-C,IL-1β,IL-6,TNF-α,p-JAK2/JAK2,p-STAT3/STAT3 levels were decreased,the HDL-C level was elevated,and the changes were more obvious in Hesperidin-H group (all P<0.05).Compared with Hesperidin-H group,the Hesperidin-H+CA1 group had hepatocyte hypertrophy,obvious steatosis,vacuolar shape,a large number of inflammatory cell infiltration,a large number of red lipid droplets,and obvious lipid accumulation,the weight,Lee’s Index,obesity rate,and TG,TC,LDL-C,IL-1β,IL-6,TNF-α,p-JAK2/JAK2,p-STAT3/STAT3 levels were increased,the HDL-C level was decreased (all P<0.05).Conclusion:Hesperidin can exert lipid-lowering effect on obese rats,which is related to the inhibition of IL-6/JAK2/STAT3 signaling pathway.

参考文献/References:

[1]NUSSBAUMEROVA B,ROSOLOVA H.Obesity and dyslipidemia[J].Curr Atheroscler Rep,2023,25(12):947-955.
[2]IACOBINI C,PUGLIESE G,BLASETTI FANTAUZZI C,et al.Metabolically healthy versus metabolically unhealthy obesity[J].Metabolism,2019,92(1):51-60.
[3]万红,燕树勋,周媛,等.五苓散加味联合二甲双胍治疗单纯性肥胖症合并脂代谢异常效果研究[J].陕西中医,2019,40(10):1367-1369.
[4]吴俊兰,袁萍.基于专利信息的中国减肥产品研发趋势分析[J].中国现代应用药学,2019,36(16):2100-2105.
[5]MOSQUEDA-SOLS A,SNCHEZ J,REYNS B,et al.Hesperidin and capsaicin,but not the combination,prevent hepatic steatosis and other metabolic syndrome-related alterations in western diet-fed rats[J].Sci Rep,2018,8(1):15100-15113.
[6]CUI F,SUN J,MI H,et al.Chronic intermittent hypobaric hypoxia improves iron metabolism disorders via the IL-6/JAK2/STAT3 and Epo/STAT5/ERFE signaling pathways in metabolic syndrome rats[J].J Trace Elem Med Biol,2023,79(1):127259.
[7]莫灿婷,唐霁,谢汉兴,等.针刺对肥胖大鼠脂肪组织M1型巨噬细胞及IL-6表达的影响研究[J].针灸临床杂志,2022,38(2):64-67.
[8]鲁慧东,李艳梅.白术内酯Ⅲ通过调节JAK2/STAT3信号通路减轻溃疡性结肠炎模型小鼠肠道损伤[J].中国病理生理杂志,2023,39(1):142-149.
[9]朱莹,徐宁.2006-2015年我国成人超重和肥胖长期变化趋势分析[J].中国药物与临床,2020,20(11):1803-1804.
[10]GENG J,NI Q,SUN W,et al.The links between gut microbiota and obesity and obesity related diseases[J].Biomed Pharmacother,2022,147(1):112678-112689.、
[11]童国相,王莎,高国应,等.肥胖患者血清Apelin水平与血糖、血脂和胰岛素抵抗的相关性分析[J].临床误诊误治,2019,32(3):90-93.
[12]曹晋,拜珂,安欣,等.超重和肥胖合并2型糖尿病微量白蛋白尿患者维生素D营养状况临床分析[J].陕西医学杂志,2021,50(7):850-853.
[13]高学坤,冯晨毅,许详,等.橙皮苷对肥胖小鼠脂肪组织脂质代谢的作用及机制[J].营养学报,2021,43(5):474-478,484.
[14]燕炯,杨佳敏,许祥,等.橙皮苷对高脂饮食诱导NAFLD小鼠及其PLIN1基因表达的影响[J].中药材,2023,46(4):1016-1020.
[15]刘庆,宋建刚,卢蓉,等.青钱柳黄酮对幼年免疫低下并肥胖大鼠血糖、血脂、免疫功能的调节作用[J].广西医学,2021,43(10):1209-1214.
[16]曾治君,凌美婷,朱鑫辉,等.黄芩对营养性肥胖大鼠血糖血脂的作用及其机理研究[J].江西中医药大学学报,2022,34(3):91-94.
[17]VEKIC J,ZELJKOVIC A,STEFANOVIC A,et al.Obesity and dyslipidemia[J].Metabolism,2019,92(1):71-81.
[18]章常华,魏悦,施旻,等.知母黄柏药对对肥胖症大鼠模型降脂作用的实验研究[J].时珍国医国药,2021,32(4):773-776.
[19]郑桃,田雪飞,胡青松,等.连翘苷对肥胖症大鼠脂代谢紊乱和氧化应激的影响及机制研究[J].医学分子生物学杂志,2023,20(1):78-83.
[20]刘岩松,祁烁,张洁,等.660 nm激光照射对肥胖小鼠代谢的影响实验研究[J].陕西医学杂志,2024,53(6):759-763.
[21]GALLO S,CHESKIN L J.Treatment of obesity:Beyond the diet[J].Gastroenterol Clin North Am,2021,50(1):113-125.
[22]KAWAI T,AUTIERI M V,SCALIA R.Adipose tissue inflammation and metabolic dysfunction in obesity[J].Am J Physiol Cell Physiol,2021,320(3):c375-c391.
[23]SCHEITHAUER T P M,RAMPANELLI E,NIEUWDORP M,et al.Gut microbiota as a trigger for metabolic inflammation in obesity and type 2 diabetes[J].Front Immunol,2020,11(1):571731-571759.
[24]王一涵,李佳睿,杜丽坤.基于炎症与糖脂代谢探讨连陈汤对肥胖小鼠体质量的影响[J].西部中医药,2023,36(11):38-42.
[25]DANG W Z,LI H,JIANG B,et al.Therapeutic effects of artesunate on lupus-prone MRL/LPR mice are dependent on T follicular helper cell differentiation and activation of JAK2-STAT3 signaling pathway[J].Phytomedicine,2019,62(1):152965-152982.
[26]张丽芳,胡芳,程赛博,等.定心方Ⅲ号方调控JAK2/STAT3通路对肥胖小鼠脂肪炎症的影响[J].中国中西医结合杂志,2022,42(8):979-986.
[27]喻松仁,舒晴,白洋,等.温胆汤对肥胖痰湿证大鼠相关炎症因子及JAK2/STAT3通路关键分子STAT3表达的影响[J].中国实验方剂学杂志,2019,25(6):39-44.

相似文献/References:

[1]周松兰,杨晓瑞,熊清,等.Nesfatin-1激活PPARγ信号通路调节脂代谢改善大鼠肥胖症实验研究[J].陕西医学杂志,2025,54(6):748.[doi:DOI:10.3969/j.issn.1000-7377.2025.06.005]
 ZHOU Songlan,YANG Xiaorui,XIONG Qing,et al.Nesfatin-1 regulates lipid metabolism and improves obesity in rats by activating PPARγ signaling pathway[J].,2025,54(6):748.[doi:DOI:10.3969/j.issn.1000-7377.2025.06.005]
[2]纪亚楠,李旭华,冯云,等.橙皮苷对牙髓炎大鼠牙髓组织损伤的作用及机制实验研究[J].陕西医学杂志,2025,54(8):1017.[doi:DOI:10.3969/j.issn.1000-7377.2025.08.002]
 JI Yanan,LI Xuhua,FENG Yun,et al.Effect and mechanism of hesperidin on pulp tissue damage in rats with pulpitis[J].,2025,54(6):1017.[doi:DOI:10.3969/j.issn.1000-7377.2025.08.002]

备注/Memo

备注/Memo:
河北省中医药类科学研究课题(2024053)
更新日期/Last Update: 2025-06-04