摘要
目的:观察二甲双胍对糖尿病小鼠肝库普弗细胞(KCs)炎症反应的抑制作用,探讨其对肝KCs吞噬功能的改善作用,阐明二甲双胍对糖尿病小鼠肝KCs的保护机制。方法:16只C57BLKS/J db/db小鼠分为糖尿病组和糖尿病加二甲双胍组,16只C57BLKS/J db/m小鼠分为非糖尿病组和非糖尿病加二甲双胍组,每组8只。分别取各组小鼠肝KCs体外培养,透射电镜观察KCs超微结构,ELISA法定量测定KCs中白细胞介素6(IL-6)、肿瘤坏死因子α(TNF-α)和γ干扰素(INF-γ)水平,Western blotting法检测KCs中细胞间黏附分子1 (ICAM-1)蛋白表达水平,Transwell小室法检测KCs的中性粒细胞趋化功能,倒置显微镜下观察KCs吞噬能力。结果:糖尿病小鼠KCs中线粒体和粗面内质网(RER)的数量减少,RER扩张,线粒体肿胀及脂滴增多。与非糖尿病组比较,糖尿病组小鼠KCs中IL-6、TNF-α、INF-γ水平和ICAM-1表达水平明显升高(P<0.05),KCs的中性粒细胞趋化能力增强(P<0.05),吞噬能力减弱(P<0.05)。与糖尿病组比较,糖尿病加二甲双胍组小鼠KCs中IL-6、TNF-α、INF-γ水平和ICAM-1表达水平明显降低(P<0.05),KCs的中性粒细胞趋化能力减弱(P<0.05),吞噬能力增强(P<0.05)。结论:二甲双胍可以抑制糖尿病小鼠肝KCs的炎症反应并改善其吞噬功能,对肝KCs起到保护作用。
Objective:To observe the inhibitory effect of metformin on the inflammatory response of Kupffer cells(KCs)of liver in the diabetic mice,and to explore its improvement on the phagocytic function of KCs,and to elucidate the protective mechanism of metformin on the KCs in the diabetic mice.Methods:The C57BLKS/J db/db mice were divided into diabetes group and diabetes+metformin group,and the C57BLKS/J db/m mice were divided into non-diabetes group and non-diabetes+metformin group,8 mice in each group.The KCs were cultured in vitro and the changes of ultrastrustures of KCs were observed by transmission electron microscope.The levels of interleukin 6(IL-6),tumor necrosis factorα(TNF-α)andγ-interferon(INF-γ)in the KCs were detected by ELISA.The expression levels of intercellular adhesion molecule 1(ICAM-1)protein in the KCs was detected by Western blotting method.Transwell chamber assay was used to detect the neutrophil chemotaxis ability of the KCs,and the phagocytic ability of KCs was observed under inverted microscope.Results:The number of mitochondria and rough endoplasmic reticulum(RER)in the KCs of the diabetic mice was reduced,the RER expanded,the mitochondria swelled,and the lipid droplets were increased.Compared with non-diabetes group,the levels of IL-6,TNF-α,INF-γand the expression level of ICAM-1 in the KCs of the mice in diabetes group were significantly increased(P<0.05);the neutrophil chemotaxis ability of the KCs was enhanced(P<0.05),and the phagocytic ability was decreased(P<0.05).Compared with diabetes group,the levels of IL-6,TNF-α,INF-γand the expression level of ICAM-1 in the KCs in diabetes+metformin group were significantly decreased(P<0.05);the neutrophil chemotaxis ability was decreased(P<0.05),and the phagocytic ability was enhanced(P<0.05).Conclusion:Metformin can inhibit the inflammatory response of KCs in the diabetic mice and improve its phagocytic function and protect the KCs.
作者
王睿斌
赵艳杰
宋清坤
盛敏佳
WANG Ruibin;ZHAO Yanjie;SONG Qingkun;SHENG Minjia(Department of Emergency,Beijing Shijitan Hospital,Capital Medical University,Beijing 100038,China;Department of Oncology,Beijing Shijitan Hospital,Capital Medical University,Beijing 100038,China;Department of Scientific Research,Beijing Shijitan Hospital,Capital Medical University,Beijing 100038,China;Department of Obstetris and Gynecology,China-Japan Union Hospital,Jilin University,Changchun 130033,China)
出处
《吉林大学学报（医学版）》
CAS
CSCD
北大核心
2019年第1期39-44,218,共7页
Journal of Jilin University：Medicine Edition
基金
铁道部科技研究开发计划项目资助课题(J2017Z604)
关键词
二甲双胍
糖尿病
实验性
库普弗细胞
炎症反应
metformin
diabetes mellitus,experiment
Kupffer cells
inflammatory response
