慢性应激诱导DPP-4表达及对脂肪炎症和代谢的影响

doi:10.13418/j.issn.1001-165x.2020.04.014

中国临床解剖学杂志 ›› 2020, Vol. 38 ›› Issue (4): 438-443.doi: 10.13418/j.issn.1001-165x.2020.04.014

慢性应激诱导DPP-4表达及对脂肪炎症和代谢的影响

阿不来克木·马合木提¹，　买买提·依斯热依力^2,3，　艾克拜尔·艾力^2,3，　李义亮³，　阿孜古丽·阿力木江²，　闫晶³，　克力木·阿不都热依木^2,3

1. 新疆维吾尔自治区人民医院急诊创伤外科；　2. 新疆维吾尔自治区人民医院自治区普外微创研究所；
3. 新疆维吾尔自治区人民医院微创、疝和腹壁外科，乌鲁木齐 830001

收稿日期:2019-05-15 出版日期:2020-07-25 发布日期:2020-07-29
通讯作者: 买买提·依斯热依力，医师，副研究员，E-mail:maimaiti727@sina.com
作者简介:阿不来克木·马合木提（1978-），男，学士，主治医师，研究方向：急诊创伤及胃肠道疾病的诊疗，Tel：13899833283，E-mail:858527242@qq.com
基金资助:
新疆维吾尔自治区自然科学基金（2018D01C134）；新疆维吾尔自治区引进高层次人才天池百人计划项目（201939）

The chronic stress induced expression of DPP-4 and its role in adipose inflammation and glucose metabolism

ABULAIKEMU·Mahemuti¹, MAIMAITI·Yisireyili^2,3, AIKEBAIER·Aili^2,3, LI Yi-liang³, AZIGULI -Alimujiang², YAN Jing³, KELIMU·Abudureyimu^2,3

1. Department of Emergency and Traumatic Surgery, 2. Research Institute of General and Minimally Invasive Surgery, 3. Department of Minimally Invasive Surgery, Hernia and Abdominal Wall Surgery, People's Hospital of Xinjiang Uygur Autonomous Region, Urumqi 830001, China

Received:2019-05-15 Online:2020-07-25 Published:2020-07-29

摘要/Abstract

摘要： 目的　分析慢性应激诱导脂肪二肽基肽酶-4（DPP-4）表达及对脂肪炎症和糖代谢的影响。方法　雄性SPF级小鼠20只随机分慢性应激（Stress）组和正常对照（Control）组。Stress组小鼠每天在自制式束缚器中限制活动2 h，实验持续14 d。采用免疫组化方法检测巨噬细胞表面标志物（CD11b）在脂肪中的表达，实时定量PCR法检测脂肪组织中DPP-4、细胞因子（Adiponectin、MCP-1、IL-6、TNF-α）及糖代谢（IRS-1、GLUT-4）等指标的mRNA的相对表达量；ELISA法检测DPP-4酶活性及GLP-1浓度。结果　Stress小鼠腹部白色脂肪组织（WAT）与Control组相比显著的退缩及其重量显著降低（P<0.001）。Stress组WAT出现大量的单核细胞、中性粒细胞浸润反应和炎症性改变；Stress显著降低Adiponectin的表达，并显著增高MCP-1、IL-6、TNF-α的mRNA表达及其血液中的浓度（P<0.001）；Stress组WAT组织中DPP-4 mRNA表达及其血液中的活性显著增高，而GLP-1血液中的浓度显著降低（P<0.001）；Stress组WAT组织中IRS-1及GLUT-4的mRNA水平显著低于Control组（P<0.001）。结论　慢性应激诱导脂肪DPP-4异常表达，进而引起脂肪炎症和糖代谢异常等反应。

关键词: 慢性应激, , , 二肽基肽酶-4, , , 脂肪细胞因子, , , 炎症, , , 糖代谢

Abstract: Objective　To analyze chronic stress induced dipeptidyl peptidase-4 (DPP-4) expression and its role in adipose inflammation and glycometabolism.　Methods　20 male SPF mice were randomly divided into two groups: a stress group and a control group. Mice in the stress group were restrained in our own restraint device for 2 hours per day and lasted for 14 days. The expression of macrophage surface marker (CD11b) in adipose tissue was detected by immunohistochemistry. The expression of DPP-4, adipocytokines (Adiponectin, MCP-1, IL-6, TNF-α) in adipose tissue and the expressions of glucose metabolism molecules (IRS-1, GLUT-4) were further detected by RT-PCR. The enzymatic activity of DPP-4 and the concentration of GLP-1 were detected by ELISA.　Results　The white adipose tissue (WAT) of the stress group mice significantly retracted and WAT weight significantly reduced (P<0.001). WAT in the stress group showed a large number of monocytes, neutrophils infiltration and inflammatory changes. Mice in the stress group significantly decreased the expression of Adiponectin and significantly increased the expression of MCP-1, IL-6 and TNF-α (P<0.001). DPP-4 expression in WAT tissues and its activity in blood increased significantly in the stress group, but the concentration of serum GLP-1 decreased significantly (P<0.001). The mRNA level of IRS-1 and mRNA level of GLUT-4 in WAT of the stress group were significantly lower than that of the control group (P<0.001). Conclusions　Chronic stress induced abnormal expression of DPP-4 in adipose tissue, which can lead to adipose inflammation and abnormal glycometabolism.

Key words: Chronic stress, 　Dipeptidyl peptidase-4, 　Adipocytokine, 　Inflammation, Glycometabolism

中图分类号:

R335.9

阿不来克木·马合木提, 买买提·依斯热依力, 艾克拜尔·艾力, 李义亮, 阿孜古丽·阿力木江, 闫晶, 克力木·阿不都热依木. 慢性应激诱导DPP-4表达及对脂肪炎症和代谢的影响[J]. 中国临床解剖学杂志, 2020, 38(4): 438-443.

ABULAIKEMU·Mahemuti, MAIMAITI·Yisireyili, AIKEBAIER·Aili, LI Yi-liang, AZIGULI -Alimujiang, YAN Jing, KELIMU·Abudureyimu. The chronic stress induced expression of DPP-4 and its role in adipose inflammation and glucose metabolism[J]. Chinese Journal of Clinical Anatomy, 2020, 38(4): 438-443.

参考文献 16

[1]	Carrier A. Metabolic syndrome and oxidative stress: a complex relat-ionship[J]. Antioxid Redox Signal, 2017, 26 (9):429-431.
[2]	Liu YZ, Wang YX, Jiang CL. Inflammation: the common pathway of stress-related diseases[J]. Front Hum Neurosci, 2017, 11: 316.
[3]	Secrest MH, Udell JA, Filion KB. The cardiovascular safety trials of DPP-4 inhibitors, GLP-1 agonists, and SGLT2 inhibitors[J]. Trends Cardiovasc Med, 2017, 27(3):194-202.
[4]	Dandekar A, Mendez R, Zhang K. Cross Talk Between ER Stress, Oxidative Stress, and Inflammation in Health and Disease[J]. Methods Mol Biol, 2015,1292(3):205-214.
[5]	Sharma D, Verma S, Vaidya S, et al. Recent updates on GLP-1 agonists: Current advancements & challenges[J]. Biomed Pharmacother, 2018, 108(88):952-962.
[6]	Yisireyili M, Uchida Y, Yamamoto K, et al. Angiotensin receptor blocker irbesartan reduces stress-induced intestinal inflammation via AT1a signaling and ACE2-dependent mechanism in mice[J]. Brain Behav Immun, 2018, 69 (010):167-179.
[7]	Yisireyili M, Takeshita K, Hayashi M, et al. Dipeptidyl peptidase- IV inhibitor alogliptin improves stress-induced insulin resistance and prothrombotic state in a murine model[J]. Psychoneuroendocrinology, 2016, 73(4):186-195.
[8]	Takayanagi R, Uchida T, Kimura K, et al. Evaluation of drug efficacy of GLP-1 receptor agonists and DPP-4 inhibitors based on target molecular binding occupancy[J]. Biol Pharm Bull, 2018, 41(2):153-157.
[9]	Senyigit A, Tabak O, Orhanoglu T, et al. Glucagon-like peptide-1 levels and dipeptidyl peptidase-4 activity in type 2 diabetes[J]. Clin Invest Med, 2017, 40(5):E188-E199.
[10]	买买提·依斯热依力, 买买提艾力·艾则孜, 吾布力卡斯木·吾拉木,等. 慢性束缚应激诱导脂肪Nox-4表达及其在脂肪炎症发生中的作用[J]. 中华内分泌代谢杂志, 2019, 35(5) : 410-416.
[11]	胡仁明，谢颖，鹿斌，等. 2型糖尿病患者高发“代谢性炎症综合征”[J]. 中华内分泌代谢杂志，2016，32(1): 27-30.
[12]	Burhans MS, Hagman DK, Kuzma JN, et al. Contribution of adipose tissue inflammation to the development of type 2 diabetes mellitus[J]. Compr Physiol, 2018, 9(1):1-58.
[13]	Yahagi K, Kolodgie FD, Lutter C, et al. Pathology of human coronary and carotid artery atherosclerosis and vascular calcification in diabetes mellitus[J]. Arterioscler Thromb Vasc Biol, 2017, 37(2):191-204.
[14]	Kacso T, Bondor CI, Rusu CC, et al. Adiponectin is related to markers of endothelial dysfunction and neoangiogenesis in diabetic patients[J]. Int Urol Nephrol, 2018, 50 (9):1661-1666.
[15]	买买提·依斯热依力，阿孜古丽·阿力木江，吾布力卡斯木·吾拉木,等.Nox-4在慢性束缚应激致小鼠胃黏膜炎症损伤发生中的作用[J]. 中华行为医学与脑科学杂志, 2019, 28(4):316-321.
[16]	Yisireyili M, Hayashi M, Wu H, et al. Xanthine oxidase inhibition by febuxostat attenuates stress-induced hyperuricemia, glucose dysmetabolism, and prothrombotic state in mice[J]. Sci Rep, 2017, 7(1):1266.

慢性应激诱导DPP-4表达及对脂肪炎症和代谢的影响

The chronic stress induced expression of DPP-4 and its role in adipose inflammation and glucose metabolism

可视化

摘要/Abstract

引用本文

使用本文

参考文献 16

相关文章 15

Metrics

本文评价

推荐阅读 0

[1]	江剑宏, 段仁鹏, 李晓锋. 国人胆道三维重建解剖变异应用研究[J]. 中国临床解剖学杂志, 2024, 42(1): 1-4.
[2]	郭红志, 王瑜, 张加琪, 梁海彬, 马梓玮, 冯伟, 吴忧, 司子燚. 血管铸型结合CT三维模型评估先兆子痫胎盘血管结构[J]. 中国临床解剖学杂志, 2024, 42(1): 5-10.
[3]	李佳伟, 张静, 李灿然, 兰文杰, 籍庆余, 郭志勇, 张云凤, 刘启, 陈清威, 李筱贺. 蒙古族人群股骨近端解剖参数X线测量[J]. 中国临床解剖学杂志, 2024, 42(1): 11-16.
[4]	李琨, 张燕, 郭冉, 郝咪咪, 吴轩宇, 徐艺芳, 王超群, 马文童, 张灵淇, 杨宏宇, 李志军, 张少杰, 王星. 儿童及青少年枕颈角与后枕颈角数字化测量及其临床意义[J]. 中国临床解剖学杂志, 2024, 42(1): 17-20.
[5]	李文, 杨思艺, 黄蕾, 卿霁雯, 蒋松涛, 张磊. 基于MRI探讨Lisfranc韧带的形态学特点及临床意义[J]. 中国临床解剖学杂志, 2024, 42(1): 21-25.
[6]	李凡凡, 徐阳, 王晓旭. 紫草素调节Nrf2/HO-1信号通路对实验性大鼠肉芽肿性小叶性乳腺炎的治疗作用研究[J]. 中国临床解剖学杂志, 2024, 42(1): 26-32.
[7]	王兴航, 丁佳媛, 李放, 包翠芬, 阎丽菁. 人参皂苷Rg1通过抑制NLRP3炎症小体途径减轻氧糖剥夺/复供后小胶质细胞炎症反应[J]. 中国临床解剖学杂志, 2024, 42(1): 33-41.
[8]	程莹莹, 武建军, 蔡海燕, 焦旭文, 马江波, 丁银秀. 体外炎性诱导星形胶质细胞激活及功能分析[J]. 中国临床解剖学杂志, 2024, 42(1): 42-46.
[9]	祁志, 杨力, 贾秋叶, 陈浩伦, 段兆达, 吴春云. 依达拉奉经MAPKs通路对脂多糖激活的小胶质细胞Sirt3表达调控[J]. 中国临床解剖学杂志, 2024, 42(1): 47-53.
[10]	张晶晶, 王洪新. 黄芩苷通过PDGF/P38 MAPK信号通路对肺动脉高压大鼠的保护作用[J]. 中国临床解剖学杂志, 2024, 42(1): 54-58.
[11]	乐钦, 陈荣丽, 熊婧熙, 王婷怡, 蔡志恒, 易秋实, 曾心怡. 白芨多糖对大鼠跨区皮瓣choke区的影响[J]. 中国临床解剖学杂志, 2024, 42(1): 59-64.
[12]	李笑予, 张磊, 付磊, 李东波, 汪国友. 三步接骨法治疗Sanders Ⅱ型跟骨骨折的有限元研究[J]. 中国临床解剖学杂志, 2024, 42(1): 65-70.
[13]	吴研飞, 马剑雄, 卢斌, 王颖, 柏豪豪, 靳洪震, 马信龙. CT后处理技术重建CT值与终板抗压强度的相关性研究[J]. 中国临床解剖学杂志, 2024, 42(1): 71-76.
[14]	庄万强, 唐毅, 骆勇刚, 张辉. 关节镜联合胫骨高位截骨术对髌骨位置及髌股关节功能影响的早中期回顾性研究[J]. 中国临床解剖学杂志, 2024, 42(1): 77-82.
[15]	罗鹰, 窦伟誉, 吴小杭, 陈璟昆, 彭昌贵, 潘剑英 . 微创海马钢板内固定治疗跟骨骨折并发症的影响因素[J]. 中国临床解剖学杂志, 2024, 42(1): 83-88.