[1]张　恒a,袁　莉,王　佩a,等.血管生成素样蛋白 2（ANGPTL2）对大鼠局灶性脑缺血 /再灌注损伤的炎症保护机制研究[J].现代检验医学杂志,2019,34(06):32-35.[doi:10.3969 ／ j.issn.1671-7414.2019.06.008]
　ZHANG Henga,YUAN Li,WANG Peia,et al.Study on the Inflammatory Protective Mechanism of Angiogenin-Like Protein 2 （ANGPTL2）on Focal Cerebral Ischemia/Reperfusion Injury in Rats[J].Journal of Modern Laboratory Medicine,2019,34(06):32-35.[doi:10.3969 ／ j.issn.1671-7414.2019.06.008]
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血管生成素样蛋白 2（ANGPTL2）对大鼠局灶性脑缺血 /再灌注损伤的炎症保护机制研究()
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《现代检验医学杂志》[ISSN:/CN:]

卷:
第34卷
期数:
2019年06期
页码:
32-35
栏目:
论著
出版日期:
2019-12-30

文章信息/Info

Title:
Study on the Inflammatory Protective Mechanism of Angiogenin-Like Protein 2 （ANGPTL2）on Focal Cerebral Ischemia/Reperfusion Injury in Rats
文章编号:
1671-7414（2019）06-032-05
作者:
张　恒1a; 袁　莉2; 王　佩1a; 吴晓康3; 雷华斌1b;  焦飞燕4
（1. 北京中医药大学孙思邈医院a. 检验科；b. 脑病科，陕西铜川　727031；2. 西安交通大学第一附属医院检验科， 西安　710061；3. 西安交通大学第二附属医院检验科，西安　710000；4. 陕西省第四人民医院，西安　710043）
Author(s):
ZHANG Heng1a;  YUAN Li2;  WANG Pei11a;  WU Xiao-kang3;  LEI Hua-bin1b;  JIAO Fei-yan4
(1a.Department of Clinical Laboratory;1b. Department of Encephalopaty, Sun Simiao Hospital, Beijing University of Traditional Chinese Medicine,Shaanxi Tongchuan 727031, China;2.Department of Clinical Laboratory, the First Affiliated Hospital of Xi’an Jiaotong University, Xi’an 710061, China,3.Department of Clinical Laboratory, the Second Affiliated Medicine of Xi’an Jiaotong University, Xi’an 710000, China; 4. the Fourth Peple’s Hospital of Shaanxi, Xi’an 710043, China)
关键词:
血管生成素样蛋白2; 脑缺血/ 再灌注; 急性脑损伤; 血脑屏障
分类号:
R-332
DOI:
10.3969 ／ j.issn.1671-7414.2019.06.008
文献标志码:
A
摘要:
目的　探讨血管生成素样蛋白2（Angiogenin-like protein 2，ANGPTL2）在大鼠缺血/ 再灌注后脑损伤过程中 的炎症保护机制。方法　选择健康雄性Wister 大鼠60 只，建立大鼠局灶性脑缺血/ 再灌注损伤模型，随机分为假手术 组和ANGPTL2 组。建模后6 , 12 , 24 , 48 和72 h 后，采用实时定量PCR（real-time quantitative PCR）以及苏木精- 伊 红染色法（hematoxylin-eosin，HE）检测每组大鼠体内ANGPTL2 的表达水平。在建模48 h 后分别记录每组大鼠的神经 功能评分，检测其脑组织含水量、血脑屏障（blood brain barrier，BBB）通透性以及脑梗死体积。采用酶联免疫吸附法(enzyme linked immunosorbent assay，ELISA) 在建模前(T0)、建模后2 h(T1)、建模后6 h(T2)、建模后12 h(T3) 和建模后24 h(T4) 分别检测大鼠血清中S-100β、肿瘤坏死因子-α（tumor necrosis factor α，TNF-α）和白细胞介素-1（interleukin-1， IL-1）的表达水平。结果　在缺血30 和90 min 中的ANGPTL2 组再灌注6，12，24，48 和72 h 的ANGPTL2 mRNA 表 达水平均高于假手术组。ANGPTL2 组大鼠的脑组织含水量、伊水思蓝含量和脑梗死体积均显著低于假手术组，而神经 功能评分高于假手术组，差异均有统计学意义（t =2.431~6.058, 均P ＜ 0.05）。相较于T0，大鼠在T1 时的S-100B 显著 增加，随着建模时间的延长，S-100β 水平逐渐降低，并且与T0 的差异均有统计学意义（t =2.346~3.649, 均P ＜ 0.05）。 相较于T0，ANGPTL2 组大鼠在T1，T2，T3，T4 时血清中的TNF-α 和IL-1 水平均显著升高，且差异具有统计学意义 （t =5.036~9.775, 均P ＜ 0.05）。结论　ANGPTL2 可以降低大鼠局灶性脑缺血/ 再灌注后血脑屏障的通透性，并减轻脑 血管炎症反应，对脑缺血/ 再灌注损伤具有保护作用。
Abstract:
Objective　To investigate the protective mechanism of angiopoietin-like protein 2 (ANGPTL2) in brain injury induced by ischemia/reperfusion in rats. Methods　60 healthy male Wister rats were selected to establish focal cerebral ischemia/ reperfusion injury model. They were randomly divided into sham operation group, and ANGPTL2 group saline group. After 6, 12, 24, 48 and 72 hours, Real-Time Quantitative PCR and Hematoxylin-Eosin staining were used to detect the expression level of ANGPTL2 in each group of rats. After 48 hours of modeling, the neurological function scores of each group were collected, and the brain water content, blood brain barrier (BBB) permeability and cerebral infarction volume of each group were measured. Enzyme linked immunosorbent assay (ELISA) was used to detect S-100β, tumor necrosis factor α (TNF-α) and interleukin-1 (IL-1) expression level in rat serum before modeling (T0), 2 hours after modeling (T1), 6 hours after modeling (T2), 12 hours after modeling (T3), 24 hours after modeling (T4). Results　The mRNA expression level of ANGPTL2 in the ANGPTL2 group at 6, 12, 24, 48 and 72 hours after reperfusion was higher than that in the sham group at 30 and 90 min. The brain water content,Evans blue content and cerebral infarction volume of ANGPTL2 group were significantly lower than that of the sham group, and the neurological function score of ANGPTL2 groups was significantly higher than that of the sham group (t =2.431~6.058, all P < 0.05). Compared with T0, S-100 increased significantly at T1. With the extension of modeling time, the S-100β level gradually decreased, and the difference with T0 was statistically significant (t =2.346~3.649, all P <0.05). Compared with T0, the levels of TNF-α and IL-1 in the serum of ANGPTL2 group were significantly increased at T1, T2, T3 and T4, and the difference was statistically significant (t =5.036~9.775，P <0.05). Conclusion　ANGPTL2 can reduce the permeability of blood-brain barrier after focal cerebral ischemia/reperfusion in rats, and alleviate cerebrovascular inflammatory reaction, which has protective effect on cerebral ischemia/reperfusion injury.

参考文献/References:

[1]　左林, 赵佳, 姜小建, 等. 缺血性脑血管病患者血清 同型半胱氨酸、叶酸和维生素B12 水平与头颈部血 管狭窄的相关性研究[J]. 现代检验医学杂志, 2017, 32(2):23-25，29. ZUO Lin, ZHAO Jia, JIANG Xiaojian, et al. Correlation study between serum homocysteine, folate,vitamin b12 levels and head and neck vascular stenosis in patients with ischemic cerebrovascular disease[J]. Journal of Modern Laboratory Medicine, 2017, 32(2):23-25，29.
[2]　曾燕, 张丹, 姜丽萍, 等. 嗜铬粒蛋白A 衍生多肽 CGA47-66 抑制脓毒症小鼠血脑屏障通透性增加[J]. 中华危重病急救医学, 2016，28(2):122-126. ZENG Yan, ZHANG Dan, JIANG Liping, et al. Chromogranin A derived peptide CGA47-66 inhibits hyperpermeability of blood brain barrier in mice with sepsis[J]. Chin Crit Care Med, 2016，28(2):122-126.
[3]　董豪杰. 血管生成素对miR-141 的调控作用及其在 血管生成中的功能[D]. 杭州：浙江大学, 2014. DONG Haojie. The regulation of angiogenin on miR-141 expression and its role in angiogenesis[D]. Hangzhou: Zhejiang University, 2014.
[4]　杨洪强, 朱杰, 王中群, 等. 血管生成素样蛋白2 促 进ApoE-/- 小鼠动脉粥样硬化内膜钙化[J]. 中国动脉 硬化杂志, 2015, 23(8):757-762. YANG Hongqiang, ZHU Jie, WANG Zhongqun, et al. Angiopoietin-like 2 promotes atherosclerotic calcification in aortic artery ApoE-/- mice[J]. Chin J Arterioscler, 2015, 23(8):757-762.
[5]　李礼, 胡娟玉, 于正清, 等. 血管生成素样蛋白1 和 2 水平在胃癌患者中的表达及临床意义[J]. 现代检 验医学杂志, 2015, 30(2):55-57. LI Li, HU Juanyu, YU Zhengqing, et al. Expression and clinical significance of angiopoietin-like protein 1 and 2 in patients with gastric cancer [J]. Journal of Modern Laboratory Medicine, 2015, 30(2):55-57.
[6]　刘玉林, 黄晓楠, 赵琪林, 等. RI 与ANG 相互作用 对BALB/C 裸鼠人膀胱癌移植瘤生长转移及PI3K/ AKT/mTOR信号通路的影响[J]. 现代检验医学杂志, 2018, 33(4):34-38.　LIU Yulin, HUANG Xiaonan, ZHAO Qilin, et al. Effects of interaction of ribounclease inhibitor and human angiogenin on the growth of transplanted balb/ c bladder cancer and the expression of PI3K/AKT/ mToR[J]. Journal of Modern Laboratory Medicine, 2018, 33(4):34-38.
[7]　郭玲玉, 张俊峰. 血管生成素样蛋白2 在心血管疾病 的研究进展[J]. 医学综述, 2016, 22(2):235-238. GUO Lingyu, ZHANG Junfeng. Research progress of angiopoietin-like protein 2 in cardiovascular diseases[J]. Med Recapit, 2016, 22(2):235-238.
[8]　高轩, 李洪亮, 李永秋, 等. 血管生成素-1 对大鼠局 灶性脑缺血/ 再灌注后血脑屏障的保护作用[J]. 中 华实验外科杂志, 2014, 31(6):1289-1291. GAO Xuan, LI Hongliang, LI Yongqiu, et al. The protective role of angiopoietin-1 in bloodbrain barrier permeability after cerebral ischemia reperfusion in rats[J]. Chinese Journal of Experimental Surgery, 2014, 31(6):1289-1291.
[9]　TAZUME H, MIYATA K, TIAN Zhe, et al. Macrophage- derived angiopoietin-like protein 2 accelerates development of abdominal aortic aneurysm[J]. Arteriosclerosis Thrombosis & Vascular Biology, 2012, 32(6):1400-1409.
[10] HORIO E, KADOMATSU T, MIYATA K, et al. Role of endothelial cell-derived angptl2 in vascular inflammation leading to endothelial dysfunction and atherosclerosis progression[J]. Arteriosclerosis Thrombosis & Vascular Biology, 2014, 34(4):790-800.
[11] 王文涛, 石秋艳, 王翠兰, 等. 脑梗死急性期血浆 NSE, S-100b 蛋白浓度变化与脑水肿关系的研究[J]. 中华中医药学刊, 2015, 33(9):2249-2251. WANG Wentao, SHI Qiuyan, WANG Cuilan, et al. Cerebral infarction acute plase serum NSE and S-100b protein concentration change wiht findings of a study of cerebral edema [J]. Chinese Journal of Traditional Chinese Medicine, 2015, 33(9):2249-2251.
[12] OLIVECRONA Z, BOBINSKI L, KOSKINEN L . ASSOCIATION of ICP, CPP, CT findings and S-100B and NSE in severe traumatic head injury. Prognostic value of the biomarkers[J]. Brain Injury, 2015, 29(4):446-454.
[13] LINSENMAIER U , WIRTH S , KANZ K G , et al. Imaging minor head injury (MHI) in emergency radiology: MRI highlights additional intracranial findings after measurement of trauma biomarker S-100B in patients with normal CCT[J]. The British Journal of Radiology, 2016,89(1061): 20150827.
[14] LAUBACH V E , SHARMA A K . Mechanisms of lung ischemia-reperfusion injury[J]. Current Opinion in Organ Transplantation, 2016, 21(3):246-252.
[15] THORIN-TERSCASES N, THORIN E. High circulating levels of ANGPTL2: Beyond a clinical marker of systemic inflammation[J]. Oxidative Medicine and Cellular Longevity, 2017, 2017:1096385.
[16] 田宇, 杨超, 徐妍妍, 等. 孕妇产后甲状腺炎患者 血清中IL-6,IFN-γ,TNF-a,TPO-Ab 含量检测的临 床意义[J]. 现代检验医学杂志, 2017, 32(6):106- 108, 111. TIAN Yu, YANG Chao, XU Yanyan, et al. Clinical Significance of detecting serum IL-6,IFN-γ,TNF-α and TPO-Ab in pregnant women of patients with postpartum thyroiditis[J]. Journal of Modern Laboratory Medicine, , 2017, 32(06):106-108.
[17] ODAGIRI H, KADOMATSU T, ENDO M, et al. The secreted protein ANGPTL2 promotes metastasis of osteosarcoma cells through integrin α5β1, p38 MAPK, and matrix metalloproteinases[J]. Science Signaling, 2014, 7(309):ra 7.

备注/Memo

备注/Memo:
基金项目：陕西省自然科学基金项目（2013JM4016）。 作者简介：张恒（1982-），女，本科，主管检验师，研究方向: 临检、生化，E-mail：tongzhheng@163.com。 通讯作者：焦飞燕（1981-），女，大学本科，主管检验师，E-mail:394531101@qq.com。收稿日期：2019-08-24
更新日期/Last Update: 2019-12-25