补锌对高脂饮食诱导糖调节受损大鼠的肝脏保护作用  

The protective roles of Znic supplementation in liver of high-fat diet-induced impaired glucose regulation rats

作　　者：王琳[1] 方芳[2] 田宏远 吕巍[1] WANG Lin;FANG Fang;TIAN Hongyuan;LU Wei(The First Hospital of Jilin University,Jilin Changchun 130021,China;Department of Nutrition and Food Hygiene,School of Public Health,Jilin University,Jilin Changchun 130021,China;NHC Key Laboratory of Radiobiology,School of Public Health,Jilin University,Changchun 130021,China)

机构地区：[1]吉林大学第一医院干部病房,吉林长春130021 [2]吉林大学公共卫生学院营养与食品卫生教研室,吉林长春130021 [3]吉林大学公共卫生学院国家卫健委放射生物学重点实验室,吉林长春130021

出　　处：《中国实验诊断学》2024年第12期1469-1475,共7页Chinese Journal of Laboratory Diagnosis

基　　金：吉林省卫生健康科技能力提升项目(2023JC021)。

摘　　要：目的通过检测补锌对高脂饮食诱导的糖调节受损(IGR)大鼠肝脏病理变化、氧化和抗氧化、线粒体损伤及凋亡的影响,探讨补锌缓解IGR肝脏损伤的机制。方法雄性Wistar大鼠80只,利用长程高脂饮食连续喂养20周建立IGR模型,并利用苏木素-伊红(HE)染色检测胰腺的病理损伤。32只IGR模型大鼠随机分成IGR模型组(IGR)、15 mg·kg^(-1)·d^(-1)补锌组(IGR+Zn_(15mg))、30 mg·kg^(-1)·d^(-1)补锌组(IGR+Zn30mg)和二甲双胍阳性药物组(IGR+Met)组,每组8只,另取8只正常Wistar大鼠作为对照组(Con)。采用HE和过碘酸雪夫染色(PAS)检测肝脏病理损伤和糖原的变化;采用生化法检测血清和肝脏组织中超氧化物歧化酶(SOD)、过氧化氢酶(CAT)、谷胱甘肽过氧化物酶(GSH-Px)和丙二醛水平的变化;分别采用碘化丙啶(propidium iodide,PI)、钙荧光探针Fluo-4、罗丹明123和AnnexinⅤ/FITC试剂盒避光染色,流式细胞术检测细胞周期百分比、钙离子浓度([Ca^(2+)]i)、线粒体膜电位(Δψm)和凋亡率。结果80只Wistar大鼠长程高脂饮食喂养20周后,32只符合IGR模型标准,成模率达到40%,并表现出一定程度的胰腺损伤。与Con组相比,IGR组肝脏内出现炎性细胞浸润,糖原减少,而补锌后,肝脏细胞炎性浸润逐渐减少,糖原逐渐恢复。另外,与Con组相比,IGR组血清和肝脏组织中SOD、CAT和GSH-Px水平明显降低,而MDA水平明显增加(P<0.05),补锌组上述指标则逐渐恢复,与IGR组相比,均具有统计学意义(P<0.05,P<0.01)。同时,与Con组相比,IGR组肝脏细胞[Ca^(2+)]i和凋亡率明显增加,而Δψm明显降低(P<0.05),补锌组上述指标向正常组恢复,特别是30 mg·kg^(-1)·d^(-1)补锌组恢复程度更明显,与IGR组相比,均具有统计学意义(P<0.05,P<0.01)。结论外源性补锌对于长程高脂饮食诱导的IGR大鼠肝脏具有保护作用,涉及到增强抗氧化能力、降低线粒体损伤和凋亡的相关机制。Objective To detect the effects of Znic supplementation on liver pathological changes,oxidation and antioxidant,mitochondrial damage and apoptosis in impaired glucose regulation(IGR)rats induced by high-fat diet,and to explore the mechanism of Znic supplementation alleviating liver damage resulted from IGR.Methods Eighty male Wistar rats were fed with long-range high-fat diet for 20 weeks to establish the IGR model,the pathological changes were detected using hematoxylin eosin(HE)in pancrease tissue.Thirty-two IGR model rats were randomly divided into IGR model group(IGR),15 mg·kg^(-1)·d^(-1)Znic supplementation group(IGR+Zn_(15mg)),30 mg·kg^(-1)·d^(-1)Znic supplementation group(IGR+Zn_(30mg))and metformin drug group(IGR+Met),there were 8 rats in each group,and an additional 8 Wistar rats were selected as Control group(Con).HE and periodic acid schiff staining(PAS)were used to detect liver pathological damage and changes in glycogen levels.Biochemical methods were used to detect changes of superoxide dismutase(SOD),catalase(CAT),glutathione peroxidase(GSH-Px),and malondialdehyde levels in serum and liver tissues.propidium iodide(PI),Calcium fluorescence probe Fluo-4,Rhodamine 123,and Annexin V/FITC kit were used to detect percentages of cell cycle,[Ca^(2+)]i,Δψm and apoptosis by Flow Cytometry.Results Eighty Wistar rats were fed with long-range high-fat diet for 20 weeks,32 rats met the IGR standards,the modeling rate reached for 40%,and IGR model rats exhibited a certain degree of pancreatic damage.Compared with Con group,there were obvious inflammatory cell infiltration in liver tissue of IGR rats,and glycogen were reduced in the liver.However,after Znic supplementation,the inflammatory infiltration of liver cells gradually decreased and glycogen gradually recovered.In addition,compared with the Con group,the levels of SOD,CAT,and GSH-Px in the serum and liver tissues of IGR group were significantly reduced,while the levels of MDA were significantly increased(P<0.05),and the indicators described above wer

关 键 词：糖调节受损 锌 肝脏 凋亡 细胞周期 

分 类 号：R575.5[医药卫生—消化系统]