二甲双胍对糖尿病小鼠肝库普弗细胞炎症反应的抑制作用和吞噬功能的改善作用

doi:10.13481/j.1671-587x.20190108

吉林大学学报(医学版) ›› 2019, Vol. 45 ›› Issue (01): 39-44.doi: 10.13481/j.1671-587x.20190108

• 基础研究 • 上一篇

二甲双胍对糖尿病小鼠肝库普弗细胞炎症反应的抑制作用和吞噬功能的改善作用

王睿斌¹, 赵艳杰², 宋清坤³, 盛敏佳⁴

1. 首都医科大学附属北京世纪坛医院急诊科, 北京 100038;
2. 首都医科大学附属北京世纪坛医院肿瘤内科, 北京 100038;
3. 首都医科大学附属北京世纪坛医院科研处, 北京 100038;
4. 吉林大学中日联谊医院妇产科, 吉林长春 130033

收稿日期:2018-06-27 发布日期:2019-01-28
通讯作者: 宋清坤,副研究员(Tel:010-60286251,E-mail:songqingkun@aliyun.com);盛敏佳,副主任医师,硕士研究生导师(Tel:0431-84995752,E-mail:minjia-sheng@hotmail.com) E-mail:songqingkun@aliyun.com;minjia-sheng@hotmail.com
作者简介:王睿斌(1975-),男,北京市人,主治医师,医学硕士,主要从事肿瘤治疗和急诊方面的研究。

Inhibitory effect of metformin on inflammatory responseof Kupffer cells of liver in diabetic mice and its improvement on phagocytic function

WANG Ruibin¹, ZHAO Yanjie², SONG Qingkun³, SHENG Minjia⁴

1. Department of Emergency, Beijing Shijitan Hospital, Capital Medical University, Beijing 100038, China;
2. Department of Oncology, Beijing Shijitan Hospital, Capital Medical University, Beijing 100038, China;
3. Department of Scientific Research, Beijing Shijitan Hospital, Capital Medical University, Beijing 100038, China;
4. Department of Obstetris and Gynecology, China-Japan Union Hospital, Jilin University, Changchun 130033, China

Received:2018-06-27 Published:2019-01-28
Contact: 铁道部科技研究开发计划项目资助课题（J2017Z604） E-mail:songqingkun@aliyun.com;minjia-sheng@hotmail.com

摘要/Abstract

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。

关键词: 二甲双胍, 糖尿病,实验性, 库普弗细胞, 炎症反应

Abstract: 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 factor α(TNF-α)and γ-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-γ and 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-γ and 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.

Key words: metformin, diabetes mellitus,experiment, Kupffer cells, inflammatory response

中图分类号:

R587.1

王睿斌, 赵艳杰, 宋清坤, 盛敏佳. 二甲双胍对糖尿病小鼠肝库普弗细胞炎症反应的抑制作用和吞噬功能的改善作用[J]. 吉林大学学报(医学版), 2019, 45(01): 39-44.

WANG Ruibin, ZHAO Yanjie, SONG Qingkun, SHENG Minjia. Inhibitory effect of metformin on inflammatory responseof Kupffer cells of liver in diabetic mice and its improvement on phagocytic function[J]. Journal of Jilin University(Medicine Edition), 2019, 45(01): 39-44.

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二甲双胍对糖尿病小鼠肝库普弗细胞炎症反应的抑制作用和吞噬功能的改善作用

Inhibitory effect of metformin on inflammatory responseof Kupffer cells of liver in diabetic mice and its improvement on phagocytic function

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