严重烫伤MODS小鼠胰岛β细胞功能下降与GLP-1/GLU比值相关性研究

摘要
图/表
参考文献
相关文章 (2)

全文: PDF (3521 KB) HTML (0 KB)
输出: BibTeX | EndNote (RIS)

摘要 目的: 研究严重烫伤MODS小鼠胰岛β细胞功能下降与胰高血糖素样肽1/血糖（GLP-1/GLU）比值关系并探讨其机理,从改善肠道分泌GLP-1功能新角度,为防治严重创伤MODS胰岛β细胞功能下降提供实验依据。方法: 90只SPF级的昆明小鼠随机分为对照组（10只）、单纯烫伤组（30只）和MODS组（50只）,MODS组制作为MODS小鼠（30％体表面积III度烫伤+腹腔注射内毒素）,单纯烫伤组仅造成30％体表面积III度烫伤,对照组假烫伤。取对照组小鼠采血,单纯烫伤组及MODS组伤后1天和3天均分别随机抓取10只小鼠进行采血,伤后5天将仍然存活的小鼠全部采血。测定小鼠GLU、血浆胰岛素、GLP-1和二胺氧化酶（DAO）水平。采用稳态模式评估β细胞功能（HOMA-β）,计算并观察胰岛β细胞功能指数HOMA-β和血浆GLP-1/GLU比值变化,计算HOMA-β指数与血浆GLP-1/GLU比值相关系数。取小鼠回肠组织进行GLP-1免疫组化检测,得出肠道GLP-1的表达水平,计算并观察肠道GLP-1分泌相对血糖（肠道GLP-1/GLU）水平变化。计算小鼠血浆GLP-1/GLU与肠道GLP-1/GLU相关系数、肠道GLP-1/GLU与血浆DAO相关系数。对数据行单因素方差分析及Bonferroni检验、Kruskal-Wallis及Bonferroni检验、Spearman秩相关性分析。结果: 严重烫伤MODS小鼠伤后1天、3天、5天的HOMA-β指数、血浆GLP-1/GLU比值以及肠道GLP-1/GLU比值均明显低于对照组及单纯烫伤组同一时间点的水平;小鼠HOMA-β指数与血浆GLP-1/GLU比值呈正相关（r=0.685,P<0.001）;小鼠血浆GLP-1/GLU与肠道GLP-1/GLU呈正相关（r=0.851,P<0.001）;小鼠肠道GLP-1/GLU比值与DAO呈负相关（r=-0.732,P<0.001）。结论: 严重烫伤MODS小鼠存在胰岛β细胞功能下降及血浆GLP-1/GLU比值降低,血浆GLP-1水平相对不足与胰岛β细胞功能下降有关,肠道损害导致GLP-1分泌相对不足。保护严重烫伤MODS小鼠肠道细胞,提高血液GLP-1/GLU比值,可作为改善胰岛β细胞功能下降的重要措施。

	服务

	把本文推荐给朋友
	加入我的书架
	加入引用管理器
	E-mail Alert
	RSS
	作者相关文章
	骆沿极
	黄志红
	肖创清
	叶春枚
	钟杰
	曹文静

关键词 ：严重烫伤, MODS, 胰岛β细胞功能下降, GLP-1/GLU, 炎症因子

Abstract：Objective To study the correlation between the reduction of islet β-cell function and the ratio of glucagon-like peptide 1/glucose (GLP-1/GLU) and explore its mechanism in severely scalded MODS mice so as to provide experimental basis for the prevention and treatment of the reduction of islet β-cell function in severely scalded MODS from a new perspective of improving the function of GLP-1 secretion in intestine. Methods 90 Kunming mice of Specific Pathogen Free (SPF) grade were randomly divided into three groups: 10 mice as the control group, 30 mice as simple scald group and 50 mice as MODS group. The mice in MODS group were made into MODS mice with 30% total body surface area Ⅲ degree scald and intraperitoneal injection of LPS. The mice in simple scald group were only inflicted with 30% total body surface area Ⅲ degree scald, and mice in the control group were sham scalded. Blood samples of mice in the control group were collected. At 1 day and 3 days after injury, 10 mice were randomly captured respectively from simple scald group and MODS group, and blood samples were collected. At 5 days after injury, blood samples of all surviving mice in scald group and MODS group were collected. The levels of GLU, plasma insulin, GLP-1 and diamine oxidase (DAO) of mice were determined. Homeostasis model assessment of β-cell function (HOMA-β) was applied, and then the index of islet β-cell function (HOMA-β) and the ratio of plasma GLP-1/GLU were calculated and observed. The correlation coefficient between HOMA-β and plasma GLP-1/GLU was calculated. The ileum tissues of mice were collected to observe the expression of GLP-1 by immunohistochemistry, and then the levels of intestinal GLP-1 secretion relative to blood glucose (intestinal GLP-1/GLU) were calculated and observed. The correlation coefficient between plasma GLP-1/GLU and intestinal GLP-1/GLU, and the correlation coefficient between intestinal GLP-1/GLU and plasma DAO were calculated. Data were statistically analyzed with one-way analysis of variance and Bonferroni test, Kruskal-Wallis and Bonferroni test, and Spearman rank correlation analysis. Results HOMA-β, plasma GLP-1/GLU and intestinal GLP-1/GLU of severely scalded MODS mice at 1, 3 and 5 days after injury were significantly lower than those of mice in the control group and simple scald group at the same time point (P<0.05). HOMA-β was positively correlated with plasma GLP-1/GLU of mice (r=0.685, P<0.001). Plasma GLP-1/GLU was positively correlated with intestinal GLP-1/GLU (r=0.851, P<0.001). Intestinal GLP-1/GLU was negatively correlated with DAO (r=-0.732, P<0.001). Conclusion The islet β-cell function and the ratio of GLP-1/GLU were decreased in severely scalded MODS mice. Insufficiency of plasma GLP-1 relative to blood glucose was correlated with the reduction of islet β-cell function. Intestinal damage led to relatively insufficient GLP-1 secretion. Protecting intestinal cells to increase the ratio of plasma GLP-1/GLU in severely scalded MODS mice can be used as an important measure to improve the reduction of islet β-cell function.

Key words： severe scalds MODS reduction of islet β-cell function GLP-1/GLU inflammatory cytokines

收稿日期: 2022-07-05

中图分类号:

R363

基金资助:长沙市中医医院（长沙市第八医院）院级科研项目（2022008）

通讯作者: 叶春枚,E-mail：373536689@qq.com

引用本文:

骆沿极, 黄志红, 肖创清, 叶春枚, 钟杰, 曹文静. 严重烫伤MODS小鼠胰岛β细胞功能下降与GLP-1/GLU比值相关性研究[J]. 金宝搏官方188学报(医学版), 2023, 20(1): 24-30. LUO Yanji, HUANG Zhihong, XIAO Chuangqing, YE Chunmei, ZHONG Jie, CAO Wenjing. Study on the correlation between the reduction of islet β-cell function and the ratio of GLP-1/GLU in severely scalded MODS mice. HuNan ShiFan DaXue XueBao(YiXueBan), 2023, 20(1): 24-30.

链接本文:

http://yxb.hunnu.edu.cn/CN/ 或 http://yxb.hunnu.edu.cn/CN/Y2023/V20/I1/24

[1] Gourd NM, Nikitas N.Multiple Organ Dysfunction Syndrome[J]. J Intensive Care Med, 2020, 35(12): 1564-1575. DOI: 10.1177/0885066619871452.
[2] Feng JY, Chien JY, Kao KC, et al.Predictors of Early Onset Multiple Organ Dysfunction in Major Burn Patients with Ventilator Support: Experience from A Mass Casualty Explosion[J]. Sci Rep, 2018, 8(1): 10939. DOI: 10.1038/s41598-018-29158-3.
[3] Wang ZK, Chen RJ, Wang SL, et al.Clinical application of a novel diagnostic scheme including pancreatic betacell dysfunction for traumatic multiple organ dysfunction syndrome[J]. Mol Med Rep, 2018, 17(1): 683-693. DOI: 10.3892/mmr.2017.7898.
[4] Sauaia A, Moore FA, Moore EE.Postinjury Inflammation and Organ Dysfunction[J]. Crit Care Clin, 2017, 33(1): 167-191. DOI: 10.1016/j. ccc.2016.08.006.
[5] Muller TD, Finan B, Bloom SR, et al.Glucagon-like peptide 1(GLP-1)[J]. Mol Metab, 2019, 30: 72-130. DOI: 10.1016/j. molmet.2019.09.010.
[6] Nadkarni P, Chepurny OG, Holz GG.Regulation of glucose homeostasis by GLP-1[J]. Prog Mol Biol Transl Sci, 2014, 121: 23-65. DOI: 10.1016/B978-0-12-800101-1.00002-8.
[7] Pan J, Xu B, Yu J.The effect of continuous blood purification on P38MAPK signaling pathway in patients with multiple organ dysfunction syndrome[J]. J Clin Lab Anal, 2019, 33(4): e22849. DOI: 10.1002/jcla.22849.
[8] Richards JE, Scalea TM, Mazzeffi MA, et al.Does Lactate Affect the Association of Early Hyperglycemia and Multiple Organ Failure in Severely Injured Blunt Trauma Patients?[J]. Anesth Analg, 2018, 126(3): 904-910. DOI: 10.1213/ANE.0000000000002626.
[9] Osterbur K, Mann FA, Kuroki K, et al.Multiple organ dysfunction syndrome in humans and animals[J]. J Vet Intern Med, 2014, 28(4): 1141-1151. DOI: 10.1111/jvim.12364.
[10] 柴家科, 盛志勇. 烧伤脓毒症与多器官功能障碍综合征临床防治的现状与思考[J]. 中华烧伤杂志, 2008, 24(5): 378-380+400. DOI: 10.3760/cma. j. issn.1009-2587.2008.05.021.
[11] 胡森, 盛志勇, 周宝桐. MODS动物模型研究进展[J]. 中国危重病急救医学, 1999, 11(8): 504-507. DOI: 10.3760/j. issn: 1003-0603.1999.08.022.
[12] Sheng Z.Prevention of multiple organ dysfunction syndrome in patients with extensive deep burns[J]. Chin J Troumatol, 2002, 5(4): 195-199.
[13] 宁丽萍, 王占科, 周方强, 等. 丙酮酸钠对严重烫伤MODS小鼠胰岛β细胞功能不全的保护作用[J]. 解放军医药杂志, 2020, 32(7): 11-15. DOI: 10.3969/j. issn.2095-140X.2020.07.003.
[14] 王裴, 冯燕海, 王顺宾, 等. 肠型脂肪酸结合蛋白在严重烧伤小鼠早期肠屏障功能损害评估中的意义[J]. 中华烧伤杂志, 2019, 35(6): 459-463. DOI: 10.3760/cma. j. issn.1009-2587.2019.06.012.
[15] 杨健莉, 刘佳, 郑志红. 常用实验大小鼠采血方法及其对实验动物福利的影响[J]. 中国比较医学杂志, 2019, 29(1): 90-94. DOI: 10.3969/j. issn.1671-7856.2019.01.016.
[16] Tasci SK, Bingol SA.GLP-1 Localisation and Proglucagon Gene Expression in Healthy and Diabetic Mouse Ileum[J]. J Vet Res, 2018, 62(2): 237-242. DOI: 10.2478/jvetres-2018-0033.
[17] Badawi O, Waite MD, Fuhrman SA, et al.Association between intensive care unit-acquired dysglycemia and in-hospital mortality[J]. Crit Care Med, 2012, 40(12): 3180-3188. DOI: 10.1097/CCM.0b013e3182656ae5.
[18] Matthews DR, Hosker JP, Rudenski AS, et al.Homeostasis model assessment: insulin resistance and beta-cell function from fasting plasma glucose and insulin concentrations in man[J]. Diabetologia, 1985, 28(7): 412-419. DOI: 10.1007/BF00280883.
[19] Zhou M, Pan Y, Jing J, et al.Association between β-cell function estimated by HOMA-β and prognosis of non-diabetic patients with ischaemic stroke[J]. Eur J Neurol, 2018, 25(3): 549-555. DOI: 10.1111/ene.13546.
[20] Drucker DJ.Mechanisms of Action and Therapeutic Application of Glucagon-like Peptide-1[J]. Cell Metab, 2018, 27(4): 740-756. DOI: 10.1016/j. cmet.2018.03.001.
[21] Klingensmith NJ, Coopersmith CM.The Gut as the Motor of Multiple Organ Dysfunction in Critical Illness[J]. Crit Care Clin, 2016, 32(2): 203-212. DOI: 10.1016/j. ccc.2015.11.004.
[22] Xia Z, Huang L, Yin P, et al.L-Arginine alleviates heat stress-induced intestinal epithelial barrier damage by promoting expression of tight junction proteins via the AMPK pathway[J]. Mol Biol Rep, 2019, 46(6): 6435-6451. DOI: 10.1007/s11033-019-05090-1.
[23] Sasaki K, Gotoh K, Miake S, et al.p32 is Required for Appropriate Interleukin-6 Production Upon LPS Stimulation and Protects Mice from Endotoxin Shock[J]. EBioMedicine, 2017, 20: 161-172. DOI: 10.1016/j. ebiom.2017.05.018.
[24] Yatim KM, Lakkis FG.A Brief Journey through the Immune System[J]. Clin J Am Soc Nephro, 2015, 10(7): 1274-1281. DOI: 10.2215/CJN.10031014.
[25] Kawai T, Akira S.The role of pattern-recognition receptors in innate immunity: update on Toll-like receptors[J]. Nat Immunol, 2010, 11(5): 373-384. DOI: 10.1038/ni.1863.
[26] Bogunovic M, Davé SH, Tilstra JS, et al.Enteroendocrine cells express functional Toll-like receptors[J]. Am J Physiol Gastrointest Liver Physiol, 2007, 292(6): G1770-1783. DOI: 10.1152/ajpgi.00249.2006.
[27] Berlanga-Acosta J, Iglesias-Marichal I, Rodríguez-Rodríguez N, et al.Review: Insulin resistance and mitochondrial dysfunction following severe burn injury[J]. Peptides, 2020, 126: 170269. DOI: 10.1016/j. peptides.2020.170269.