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。
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-αin 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.
作者
常玉平
谢琪
周腾腾
赵晋
王莉娜
程玲玲
郭丹丹
CHANG Yuping;XIE Qi;ZHOU Tengteng;ZHAO Jin;WANG Lina;CHENG Lingling;GUO Dandan(Department of Neurology,Handan People’s Hospital,Handan 056001,China;Department of Nutrition,the Fourth Hospital of Hebei Medical University,Shijiazhuang 050010,China;Department of Oncology,the Fourth Hospital of Hebei Medical University,Shijiazhuang 050010,China;Department of Traditional Chinese Medicine,Handan People’s Hospital,Handan 056001,China;Department of Obstetrics and Gynecology,Handan People’s Hospital,Handan 056001,China;Department of Pharmacy,Handan Central Hospital,Handan 057150,China)
出处
《陕西医学杂志》
2025年第6期759-764,共6页
Shaanxi Medical Journal
基金
河北省中医药类科学研究课题(2024053)。
